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PHYSICAL
P. Nath
Human Evolution
Human Genetics
Human Development
Human Adaptation
Demography
Primates Biology
Applied Anthro.
Higher Publishers Organic Evolution
PHYSICAL
ANTHROPOLOGY
P.Nath
Ex-Head of the Zoology Department
Patna University,Patna
PUBUSHER
HIGHER PUBLISHERS
339, NEHRU NA6AR, PATNA - 800 013
PHONE NO - 0612-2260588
MOBILE-9431496518
wr-tr:"qr "sRi^ t
if m^t,
#T3k#ri
9th Edition 20^11

Copyright © Author
1*‘Edition 1996 Type Set Printers
2"** Edition 2004 Rajnish New Print line Press
3^ Edition 2012 BalajiForm Anandpuri
4“* Edition 2015 Centre, Patna-13
5*^ Edition 2017 Pandooi Place
6*Edition 2018 Patna-800001
7th Edition 2018 A
8th Edition 2019
- *'i -
PREACETOTHE9lhEDmON
The new edition includes changes mainly in human evolution-newer finds of
australopthecines and revealation ofnewer facts about human-neanderthal relations
has promptd such changes in this category* Suggestions are invited.
Patna P.Nath
14th June 2019
SthEOmON
13-09-2018
TlbEDmON
14-05-2018
6thEDmON
14-08-2017
Sth EDITION
01-10-2016
PREFACET0111£4'ÊDrnON
This edition ofthe book is coming after comparatively short interval. Paucity of
time prevents me from undertaking any gross revision ofteh book which is promised in the
next edition.A few new chapters such as cultural evolution of man,gene-library etc have
been added in this edtion. 1 am overwhelmed by the interest readers have shown for this
book. I thank them all and invite their suggestions for improvement ofthis book.
In the meanwhile,I lost my father who was biggert influence in my life. The void
created cannot be filled up though lessened to some extent by arrival of my daughter-in-
laws Nistha and Suvidha in.my family.
PATNA P.NATH
17-02-2015(Shivratri)
PREFACETOTHE3*ÊDrnON
This edition included either changes or replacement ofabout fifly pages to make the
course content update.In'the meanwhile,1 lost my mother and in lawsa few years ago.This loss
was compensated to some extent by new airi\‘als in family - Rinku. S^ta,Adi. SHaurya
Suiya,Naina& Vaiun.
I am thankful to my sons Rohan and Rohit search^ net for me and typed
manuscript I am also thankful to Giandan Guha.Patna Oflktter. Patna for printing this editioa
PATNA P.NATH
05-08-2011 (Rohan's birthday)
PREFACET0HIE2-> EDITION
I am thankful to teachers and students of anthropology who liked the
book and made first edition ofthe booka success.This has inspired me to go in for
a second edition.A whole new section on demography and many topics in applied
anthropology has been added. It will certainly help students to a great extent The
In addition,several topics in the area ofhuman ecology and human genetics have
either been trimmed in order to njake it more relevant'or expanded in order tojustify
their full implications. The book is now in the hands ofreaders tojudge.
There Have been new arrivals ofpersons in my family namely sisters-in-
law Puja,Shubhra and Aradhana; nieces Shristi,Anjali,Tanvi and Aishwarya and
nephews Adarsh and twins Luv-Kush.Th^ all have proved refreshing amid long
hours ofwork.Departure ofmy loving sister,Ira,and h^husband Sachida,however,
has been a setback.
I am thankful to my father,who happens to be the publisher ofthis book,
for having opted for a quick,second revision ofthis book.I am also thankful to Dr.
-S.P. Sinha vô provided some materials on genetics.
I, finally, wish good luck to CS aspirants whose success in the subject,
and overall success, has been the main driving force for me.
PATNA P.NATH
17-09^2003
PREFACETOTHElÊOrnON
Honestly speaking,it is beyond capability ofone individual tojustify the
diverse topics included in the subject. As a teacher of genetics, evolution and
human evolution for the last twenfy years at the graduate and postgraduate level,
I have realised the problems being faced by students. Syllabi of UPSC and some
Universities have been restructured this year and several current topics have been
included. Examinees were facing difficulties in preparing for the examination. 1
thought it proper to come obt with whatever material available with me.Examinees
ofthis year have been main concern hence there has been a very quick compilation
ofthe book. This is not an excuse for any error that may have crept due to r2q>id
proof-reading and printing and I, honestly,own all such mistakes. One should not
expect much sophistication in first aid-its timing is crucial.In many ways,one will
find this book more than the first aid.
1 must thank my parents, teacher Dr. A. Nath, Deptt pfZoology, Patna
University, Father-in-law Dr. S.P. tail, Deptt. of Botany, College of^nunerce,
Patna for their kind blessings and support.1 also sincerely thank my wife Shobha,
'brothers Prem,Om,Anant,Anand,Rajesh,Kamal,and sisters Meer^ Ira, Ranjana,
Rashmi,Rajat,Smriti,and sister-in-law Sunita,sons Rohan and Rohitdnd nephews
Rishi and Gungun for their material and moral support Anant Prakash, who has
successfully compqêd in Allied Group *‘A*'Services with anthropology as one of
the optional, has spared time for proof-reading ofthis book.
PATNA P.NATH
1(M)8-1995
-iv-
CONTENTS
(A) HUMAN GENETICS 01-194
1. BranchesofHuman Genetics 1-20
2. Genetic Material ofman 21-32
3. GeneticPhenomena 33-38
4. Tools ofGenetic Stucfy 39-50
5. 'ihe Celland Cell-Division 51-51
6. Mendelism 52-63
64-66
7. StudyofAnthropogeneticVariations
67-68
8. Polygenes
9. MiiltipleAllele 69-72
10. Lethal Genes:Eugenics,Euiîcnics and Euthenics 73-76
11. Genetic Analysis ofMan(Chromosomalanalysis, 77-94
Foster-child,Co-twin method,Pedigree-Analysis,
BiodiemicalAnalyas,Rec(OTWnaiilDNAT5chnique)
12. Canmon genetic disorders ofmfen 95-97
13/ 'INvins 98 -108
14. Chromosomal Abnormalities 109-126
(Down’s S>T»dro!ae,Patau’s Syndrome,Edward’s
Syndrome,Cri-du-chat Syndrome,Klinefelter’s
Syndrome,Turner’s Syndrome,Mosaics,Hermaph
rodites and pseduohermaphrodites,Cliimaera)
15. Consanguineousmairiace(lnbreedingstudiesinlndia) 127-136
!6. GenomeImprinting 137-144
17. Gene-Therapy 145-154
18. Genetic Screening and Counselling 155-162
19. Genetic Load 163 -164
20. Genetic Laws&Ethics 165-174
21. Probablity and Statistics in Genetics 175 -181
22. Gene Mapping 182-187
23.Gene-Editing-CRISPR-Cas system,ZFN,TALEN 188 -192
24.Genomic Libriuy 193 -194
-V-
(B)ORGANIC EVOLUTION 195-290
1. Origin oflife 195-211
I 2. Evidencesofevolution 212-214
3. Lamarckism 215 - 223
4. Danvinism 224 - 233
5. Neo-Darwinism(Variation,Selection,Isolation) 234 - 248
6. Microevolution 249 - 252
7. Macroevolution 253 - 257
8. Hardy-Weinbeig law 258-263
9. Synthetictheoiy(ChangesinGene-fieqiiencyl^Drifl, 264 - 277
Migration,Inbreeding,Mutation and Selection)
10.Genetic Polymoiphism and selection. 278-287
11.Ecological nilesofEvoludon 288-290
(B) RACES 291-322
1. Race-Concept 291-294
3. BasesofRacia!Classification 295-312
3. Racism-A total myth 313 - 322
(Q HUMAN GROWTH AND DEVELOPMENT 323- 405
1. Growth and Development-Concept 323-329
2. Prenatal Growth 330-331
3. Infimcyand childhood 332-334
4. Adolescence 335 - 341
5. Post-adolescence 342 - 342
6. Senescence 343-344
7. . Genetic connolofDevelopment 345-350
8. Biochemical factors ofgrowth 351 -357
9. Herediând environment 358-366
10. Socio-Economic and Cultural FactorsofGrowth 367-370
11. Abnormaldevelopment 371 - 376
12. Human physique and somatotypes 377-385
13. Senescence and ageing theories 386-397
13. Physiological variations(Hb-level,Blood-pressure, 398-405
Respiratory function etc.)
-vi-
406-507
(D)PRIMATES BIOLOGY
1. Classification ofPrimates 406 - 425
2. Evolution and radiation ofprimates . 426 - 440
3. Human skeleton 441 - 446
4. Evolution ofprimates hand 447-452
5. Evolutionofprimatcsfootandlocomotion, 453-460
6. EvolutionofprimatesJawand dentition 461-467
468-473
7. EvoludonofprimatesBrain
474 - 481
8. Apes and Man-Differences
9. MolecularEvolutioninPrimates 482 - 495
10. Multidisciplinaiya^jproachinstiufyoffossiltypes: 496-501
Endocaststudies and fossilDNA
11. The hominization process 502 - 507
508-541
(F) HUMANECOLOGY
1. AnIntroduction 508-510
511-513
2. Adaptation to high altitude
514-516
3. Adaptation to heat
517-519
4. Adaptation to cold
520 - 526
5. Adaptation to diet
6. Adaptation against diseases . 527 - 532
533 - 535
7. ImpactofAirpollutiononhumanhealth
536-537
8. Occupational diseases
9. Effects ofsmoking 538-541
542-592
(G) APPLIEDPHYSICALANTHROPOLOGY
542-547
1. Physical Anthropology and defence-designs
2. RecombinantDNA techniquesin medicine 548 - 552
3. Forensic anthropology 553 - 560
4. Parentage detennination 561 - 568
5. Personal identification 569 - 573
574 - 577
6. Sportsanthropometry
7. Nutrition,Malnutritionandassessmentofmalnutrition 578 - 587
8. Medical Anthropology 588-592
-VII-
(H> DEMOGRAPHY 593-627
1. Nature,Scope And Relationship )^5th Physical 593 - 604
Anthropology
2. Reproductive physiology ofhumans and control 605 - 610
offeitiUty
3: Biological theories ofpopulation 611-616
4. Factors(Causes)ofdifferential fertilily-(Biological, 617-620
Economic,Social)
5. Serogenetics and cytogeneticsofreproductive 621 - 627
■ function(Male system and Female system)
(E) HUMANEVOLUnON 628-770
1. Fossil and Geological time-scale, 628-631
2. Outline ofevolution ofhominids. 632 - 636
3. Proconsul-Ehyopithecus-Sivîthecus 637-M5
4. Oreopithecus 646 - 648
5. Australopithecus-Paranthrapus 649 - 668
6. HomoHabilis 669-673
7. HomoErectus 674 - 684
8. Eariy or archaic sapiens 685 - 690
9. NeandertalMan 691 - 706
10. Modem Homo Sapiens 707-712
11. Differentrates ofsomatic evolution 713-718
12.Behavioural Modernity 719-724
13.Cultural Evolution ofMan 725 - 730
14.IndiaAsCradle-land ForHuman Evolution 731 - 731
15.Theory ofdistribution ofmodem humans 732-751
16.TheMRCA 752 - 757
17.Recentadvancesin hominid evolution 758 - 775
-VlII-
BRANCHES OF HUMAN GENETICS
CHAPTER-01
Mendel is regarded as father ofgenetics because he discovered
“Laws ofInheritance'. It does not mean that study ofgenetics did not
exist prior to Mendel. 18th and 19th century geneticists were intrested
onlyin studying pedigree patterns,cousin marriages and nature and nurture
controversy.
Maupertuis bom in France in 1698,studied inheritance ofalbinism
and polydactyly in the eighteenth century. Otto’s account in 1803 of
haemophilia in a New Hampshire family was apparently the earliest clear
description ofthe clinical features and mode ofinheritaitce ofthis disease;
it wastransmitted by healthy carrier females to their sons but never by an
affected father to his son.This mode ofinheritance was also noted in the
case ofcolour blindness by John Dalton,an English Scientist. Joseph
Adams was,perhaps,the real founder ofhuman genetics.Aphysician by
profession,he published a book entitled “A Treatise on the Supposed
Hereditary Properties of Diseases” in 1814 in which he showed
considerable insightinto many ofthe principles ofmedical genetics. On
the basisofpedigree patterns,heclearly distinguished familial(recessive)
from hereditary(dominant)disorders; he emphasised the interaction
betw^n hereditary susceptibility and precipitating environmental factors.
One ofthe first scientists to become interested in the effects of
cousin marriages was Charles Darwin,who himselfmarried a first cousin.
The results ofhis plant breeding experiment led him to conclude that the
progeny ofcrosses between unrelated organisms(outbreeding)were more
vigorous than the progeny of crosses between related organisms
(inbreeding).By the end ofnineteenth century,human genetics was still in
its infancy.
Another aspect ofhuman genetics that had occupied the minds of
workers in the beginning of20th century was nature versus nurture
controversy.In man,the distinction between the effects ofnature and
nurture were made clearfor the first time in 1875 by Sir Francis Gallon,
uncle ofCharles Darwin.Galton argued that,since identical twins have
the same genetic constitution,any difference between them must be due
I
HUMAN GKNETICS
to environment. Galton was especially interested in the inheritance of
physique and special talents.
After ^discovery ofMendelism in 1900 much effort was made to
apply these findings to man.Unfortunately,manyofthe earlierinvestigators
oversimplified things.These early investigators notonly believed that many
human diseases were explicable in terms ofthe effects ofsingle genes but
that all disorders were due either to heredity orenvironment.Nevertheless,
inauguration ofhuman genetics can be said to have occurred with the
Garrod’s data ofinborn errors ofmetabolism in 1901. Human genetics
developed slowly in the first halfof20th century during which time
populational studies dominated. Human genetics has no facilities of
controlled breeding hence mostofthe human geneticistssatisfied themselves
with pedigree analysis. However,with the discoveryofnew instruments
to analyse sub cellular components,and,discovery ofthe genetic material
itselfin the later halfof20th century,we find an accelerated growth of
human genetics which has nowramified in diverse directions.Someofthe
important branches ofhuman genetics isasfollows:
1. Biochemical And Clinical Genetics
Alkaptonuria is a very rare condition in which affected persons
excrete dnrk-coloured urine.The disease is usually recognised in infancy
because the nappies are darkly stained and,in fact, washing with soap
tends to make these .stains even more intense. The dark colour is due to
the prc.scnce ofhomogentisic acid which is broken down in normal persons
and so does no* tppear in the urine.
Sir A.v.hibald Garrod,in 1901,presented a paper in which he
studied four families affected vrith the disease,the disease appearingin the
offspring ofcousin marriages mostofthe time.Bateson suggested to him
that Alkaptonuria was a recessive disorder hence appeared most often in
the offspring ofcousin marriages.Till 1900 genetics was studied in terms
of structural traits. It was for the first time that Garrod implicated a
biochemical substance in the action ofgene,designated by Garrod as
‘inborn error ofmetabolism”.
Tliis was the beginning ofbiochemical genetics and the idea that
genes control the s>mthesis ofenzjmes which,in turn,are responsible for
2
Table 1Characteristics and some inborn errors ofmetabolism
AR and AD(autosomal recessive and dominant)XR and XD=(X-linked
recessive and dominant)
Type ofdefect Genetics Deficienten^ê Main clinical
(Usual) of defect features
(A)Amino acid
Albinism AR tyrosinase lack ofskin and
hair pigment eye
defect
Alkaptonuria AR homogentisic acid arthritis, black urine

oxidase
Phenylketonuria AR phenylalanine mental

hyroxylase retardation,fair
skin eczema,
epilepsy
[B)Carbohydrate
Galactosaemia AR galactose-1 cataracts, mental
phosphate uridyl retardation,
transferase cirrhosis. Lactose
intolerance
(C)Transport protein
Familial AD defect in ceil early coronary
hypercholesterola surface receptor artery disease
emia for low denisty
lipoprotein
Vitamin-D resistant XD renai.defect in

rickets .phosphate rickets
reabsorption
(D)Lysosomal storage disorders

Glvcoeen
Mcardle's syndrome AR musice muscle cramps
phosphoryiase
3
HUMAN GENETICS
Mucopolysaccharide
Hunter's syndrome AR iduronidase corneal clouding
SphingolipM
Niemann-Pick AR sphingomyelinase mental
disease retardation
Tay-Sachs disease AR hexosaminidase-A mental
retradation,
blindness
(E)Purine/pryimidine metabolism
Lesch-Nyhan XR hypoxanthine mental retardatipn,
disease phosphoribosyl uncontrolled
transferase movements, self-
mutilation .
(F)Porphyrias
Acute intermittent AD prophobilinogen abdominal pain,
porphyria deaminase CNS defects
(G)Miscellaneous
Cystic fibrosis AR a-1 antitrypsin enteric and lung
disease because of
thick mucus
canying outspecific biochemical processes. Beadle and Tatum provided
experimental evidence for these ideasfrom breeding experiments with the
bread mould Neurospora crassa for which they were awarded the Nobel
Prize for Medicine and Physiology in 1958.
Tlic modem eraofhuman biochemical genetics began in the 1940s
when the techniques ofpaper chromatography resulted in the discovery
and clarification ofa number ofinborn errors ofmetabolism associated
with the excretion ofabnormal quantities ofamino acids.These techniques
are still producing new discoveries ofadditional genetic diseases resulting
from blocks in the intermediary metabolism of amino acids and
carbohydrates.One example ofsuch inborn errors is phenylketonuria,
which is caused by the absence ofactivity ofthe enzyme pbenylalanihe
hydroxylase,and which results in mental retardation in the homoi^gote.
4
By.meansofa variety ofscreening programmes,afl^ted individuals fora
number ofthese defects can be discovered at birth,and,ifit is feasible,
receive special treatment to avoid the ill effects ofthe mutant gene.This
has been attempted and has been partially successful in the case ofseveral
inborn errors.The list ofnewly discovered inborn errors grows constantly,
(see table -1)In addition,a variety ofinformations have been gained on
many biochemical substancesfor example-
a. Haemoglobins:In 1949,Pauling and his co-workers estab
lished that sickle-cell haemoglobin had a different netcharge from normal
haemoglobin,and with this finding they coined the term “molecular dis-
ease This was also the first use ofthe technique which has become one
ofthe most productive in the study ofbiochemical genetics,that ofelec
trophoresis,orthe separation ofprotcins by differences in charge.In 1957,
Ingram was able to show that this difference in charge was due to the
substitution ofthe amino acid valine for glutamic acid at the sixth position
ofthe amino acid sequence ofthe beta chain ofhaemoglobin.He acliieved
this by breaking up the protein chains vrith enzymessuch as try'psin,sepa
rating t’ ^ oligopeptidesfrom each other by electrophoresis and cliroma-
tography,the latter method being dependent upon differences in solubility
rather than charges,and searching for a peptide which had changes in its
position.Once the altered peptide was located,it and its normal counter
partcould be extracted from the paper chromatograms and their amino
acid sequences determined.This technique has since resulted in the iden
tification ofover 100 different mutations occurring in the two chains of
adult haemoglobin(see genetic criteria ofraces),
b.Serum Proteins:The technique for the efficient detection of
polymorphic variantsofprotdnsand enzymes wasdiscovered in the 1950s
by Smithies and is called starch gel electrophoresis.The samplesto be
studied are inserted into a slab ofgel made by combining colloidal starch
with buffer;and anelectriccurrentisthensentthroughthe gel.Thistechnique
vrill notonly separate different proteins bytheir difference in charge,which
can be achieved in any electrophoretic medium such as paper,but will
also separate them according to their molecularsize.This is due to the fact
that die starch acts asa sieve,slowing down the movementofthe molecules
5
HUMAN GENETICS
proportionately to tfieir size. The technique results in the separation of
senim proteins into over 30majorcomponents.instead ofthe5 previously
detectable by paper electrophoresis.
Using this method.Smithies described t>\'0 polymorphisms for
common serum proteins. One ofthese is haptoglobin which serves the
function ofbinding haemoglobin abnonnally released from red cells.
The other protein initiallydiscovered to be polymorphic bySmithies
v/as the iron-binding protein ofserum,called transferrin.Since then,
there have been over20differenttransfeninsfound in differentindividuals
and their families.These,like haemoglobins,seem to differ from each
other by single amino acid substitutions.In his search for genetic variation
ofenemies demonstrable bystarch gel electrophoresis,fbrrisatthe Galton
Laboratory at University College in London discovered thatover halfof
the enzjmies screened showed such variation, with many of these
demonstrating marked poljmiorphism.Polymorphism here is defined as
the existence oftwo or more variants ofan enzyme,each occurring with a
gene frequency ofgreater than 1 percent.Although most ofthis variation
does notseem to affect thefunction ofthe enzymes,sometimes dieir activity
will be altered(inborn errors ofmetabolism),
c.Enzymes OfRBC:Among the polymorphicenzymesfound in
the red blood cells are essential for the survival ofthe cell due to their*
activity in carbohydrate metabolism.These include phosphoglucomutase,
which has been shown to be produced by three separate unlinked genes
each of which shows genetic variation, 6-phosphogluconate
dehydrogenase,and glucose 6-phosphate dehydrogenase(G-6PD),the
lattercoded by extremely mutable gene on the X-chromosome.
The initial proofin man ofthe validity ofthe Lyon's hypothesis of
genetic inactivation ofone X infemale cells was demonstrated in cultured
skin fibroblasts derived from women heterozygousfor twoelectrophoretic
typesofG-6-PD.Extracts derived from clones ofcells grown from single
fibroblaste showed onlyone orthe other variantofthis enzyme.This means
that despite the presence oftwo x chromosomes canying different genes
for G-^-PD only one ofthese is expressed in any one cell and in all ofits
offering cells.Ciartler on this basis resolved the question oforigin ofcancer
6
cells. It was found that in women,heteroz)gous for(i-6-PO.tlic uterine

tumours secrete only one tjpe ofG-6-PD.indicating origin ol tumours
from single cell. More interesting w'as the finding in case of chronic
myelogenous leukaemia (carrying Philadelphia chromosome. PIV. a
translocation product from long arm ofchromosome 22 to long arm of
chromosome 9;T 22q 9q+).Patients show the abnormality in all the
cells ofblood and marrow only,and not in other cells,
d.Placental Enzymes:Another tissue commonly used in these
studies is the placenta.It has been shown that a numberofenzymes present
in the placenta arc the productoffoetal genes.It thereby becomes possible
to obtain large quantities offoetal enzymes for study without having to
obtain it directly from a newborn child.Such a sUidy resulted,for example,
in the discoverythat placental alkaline phoshpatase,an enzme restricted
to the placenta and notfound in any other tissues,is under genetic control
offoetus,having three alleles(A,B,C)and six genotypes(AA,BB,CC.
AB.ACandBC)
2.Immunogenetics
a.Blood CellAntigens:Another prediction ofcomplete mdividual
variability was made by I^ndsteiner w'hen he discovered the ABO blood
groups.
Table 2.:ABO blood groups
Phenotype Genotype Antibodies in scrum
A AA,AO Anti-B
B BB,BO Anii-A
AB AB Neither
0 00 Anti-Aandanti-B
In addition to ABO system, Landsteiner and Weiner in 1940
discovered Rh-system.In due course oftime, more than 200 public and
200 private blood groups have been discovered. Readers are referred to
chapter’’Multiple allele” fora detailed account on blood groups,
b. HLA System: Increased activity in the field of organ
transplantation initiated the accelerated study ofhuman histocompatibility
(antigenic similarity)antigens.Witliin few years the use oftechniques derived
7
HUMAN GliNETICS
from the study ofmouse histocompatibility genes made it apparent that
the major histocompatibility differences between people are the resultof
differences at one major locus. This is identical to the situation in other
mammals in which it has been studied. This locus,referred to as HLA
(Human Leucocyte Antigen),has many alleles,each responsible for the
production of several antigens. It is highly unlikely, because ofthis
» -mplexity,that anytwo unrelated individuals will be completely identical
r.; tliis locus. HLA genes are carried not only on leucocytes buton other
tissues also.It is apparentthat unrelated individuals would rarely,ifever,
be sufBciently compatible to accept graftsform each other withoutdanger
ofrejection.It would appear,however,that the greater the similarity at
this locus,the more likely it isthata transplanted organ will not be rejected.
In addition to the obvious practical application ofstudies ofHLA there is
a great unresolved theoretical problem. What is the purpose ofsuch
enormous individual variability at one locus dealing with antigenic
specificity? A variety ofexplanations has been offered. One ofthese
proposes that this variability is associated with very refined recognition
processes which may act in the form ofsurveillance within the body for
mutantcells displayingchangesin theirsuiftu:e antigens.Sincesuchchanges
are thought to be typical ofmalignant transformation,recognition and
elimination ofsuch altered cells may be a defense against neoplasia,
c. Variability Of Immunoglobulins: Immunogenetics is
concerned with variability ofthe recognition molecules themselves.The
serum proteinsknown asimmunoglobulins,gamma globulins,orantibodies
fall into 5 classes.These are IgD,igE,IgQ IgA and IgM.Each ofthese
consists oftwo pairs ofidentical chainscalled H(heavy)and L(light).The
heavy chain detenninesthe class ofimmunoglobulin.The light chains,of
which there are two types,called kappaand lambda,are made up ofover
200amino acids about halfofwhich are constant
Theotherhalfofeach lightchain varies fiom moleculeto molecule
to an almost unlimited extent,rmd this variability in part detennines the
antilxKly specificity ofthe molecule.Similarly,itappearsthatthree-quarters
ofthe heavy chain isconstantaûn with occasionalamino acid substitutions
due to genetic variation,and one-quarter about 110 amino acids long,is
8
BRANCniiS OF I lUMAN GENETICS
extremely variable.ITiisend ofthe chain,together with the variable end of
the light chain,makes up the specific antibody site which combines with a
specific antigen.
Accurate analv’sis oftlic sequence ofamino acids in these portions
ofimmunoglobulins has shown that there is a great deal ofhomology
between the variable and constant halvesofthe light chains indicating that
they emerged from a common ancestral gene.In addition,it appears that
the heavy chain is made up offour homologous copies ofthe same gene
originally coding for halfofthe light chain.There are several hundreds
genes from -which a few arc selected to form antibodies.This is the main
reason ofantibody diversity.
From this review ofcurrent problems in human genetics,itcan be
seen that the many new techniques developed in the field have already
produced numerous advances.The major conclusion form this progress
is thatthere is virtually unlimited genetic variability in man,certainlyenough
to assure each of us of being a unique individual, biochemically and
antigenically different fiom all others,except in the case ofidentical twins.
The majorproblem to be resolved now is how this enormous heterogeneity
has comqabout,how it is maintained,and what may be its function in our
survival as a species.
3. Developmental Genetics
The zygote,the fusion product ofsperm and ovum,undergoes
mitotic divisions and thus cell number increases.Initially all cells are alike,
called embiy'onic type(without specialised function).But later on such
embryonic cells become differentiated to perform specialized functions.
Developmental genetics is concerned with the processofdifferentiation of
cells.
There exists a relationship between DNA and proteins^thesized
in the cell because it is DNA that directs protein synthesisthrough mRNA.
It is protein that characterizes a cell. Hence,it is DNA which should
ultimately be held as the factorfor differentiation,
a.Totipotcncy And NuclearTransplantation:There is no loss
ofDNA as mitotic-divisions continue and there is ample proofthat DNA
contentofthe zygote is the same asthatoflater cells. Differentiation,thus.
9
HUMAN GENETICS
is not caused due to loss ofany DNA in any ofthe differentiated cells. All
celts have same DNA and equally capable ofcausing growth.
John Guidon’sexperimentsofnucleartransplantationsin the 1960s
clearly established that all cells ofbody are equally totipotentand capable
ofcausing growth dfa zygote.It was shown that ifnucleus ofa toad’s
^gote is destroyed and replaced by its skin cell,the skin cell’s nucleus is
capable ofcausing complete growth ofzygote.Theexperiment also proved
that cytoplasm is a potent force in development because it can make the
genes‘on’or‘ofiT.The genes on in the skin cells were different when the
nucleus ofskin cells was transplanted into zygote,the cytoplasm ofthe
^gote switched the prior active genesoffand another classofgenes‘on’.
Development,atthe genetic level,is thusconsidered an interaction between
cytoplasm and genes during which Certain genes are switched ‘on’ and
‘ofT(derepressed and repressed,respectively)
b House KeepingAnd Luxury Genes:From development point
ofview genes are divided into housekeeping and luxury classes-the former
concerned with elaboration ofthose substances that are essential for all
cells e.g. membrane proteins. Such genes are switched “on” in all the
● cells. Luxury genes are concerned with specialised function ofthe cell,
henceswitched‘on”differently in differentcell.There isa definitesequence
in which different genes are activated and this is largely a function of
induction that organises the embryo.
Once a cell is differentiated,it secretes certain substances,called
inducer for other cells to differentiate. The chemical nature of such
substances seem to be nucleo-proteinous.
Development,however,does not involve only differentiation of
cells. Region formation is an equally important aspect which is probably
brought about by homeotic genes. ●
c.Homoeotic Genes:From development point ofview,genes
can be grouped as:
a Highest order genes - that define axes
b. Middle order genes - that define segments
c.Lower Order genes - that give identity to segment.
10.
branchesof
^
human genetics ●
Homoeotic genes are lower order genes.In Drosophila^ where
they have been studied in most detail,they appear to specify the diversity
ofthe different’bodysegmentsand their expression can often be shown to
occur at a particular time ofdevelopment, in a defined region ofthe
developing organism.The homoeobox or Hox genes have been shown to
be closely related structure,in that the protein produced has a closely
conserved sequence ofapproximately 60 amino acids which has been
called the homoeobox domaiiL The Hox genesappear to code for proteins
involved in the regulation ofgene expressions astranscription ftictors and
almostcertainly act by binding particular DNA sequences.Itis interesting
thatthe homoeobox genes in certain species have been found to map to a
single chromosomal cluster and the order ofthe loci ofthe homoeotic
geneson thechromosome isthesameasthe orderofthe physical segments
in the animal concerned. Homoeotic sequences have been identified in
man andhave been shown to be expressed in spinal cord during embiybnic
development(Simeone et.al. 1986)but their role in development is not
yet clear.Doubtless this area ofresearch in the nextdecade will provide
the meansto begin to understand some ofthe genetic factors controlling
development.
« d. Developmental Anomalies In Humans: Human '
developmental genetics is concerned not only with unfolding the genetic
mystery ofnormal development but seek causes and explanation on its
background for any developmental anomaly witnessed in humans.Many
examplesare known,both in animalsand man,ofmutationsand teratogens
that interfere with the normal development.Teratogen is an agent that
causescongenital abnormalities.Mutations,particular during phenocritical
period,are likely to disrupt normal embiyogenesis because all the stages
thereafter become disorderly.
In man,teratogenic agents include radiation during pregnancy,
maternal infection with rubella,treatment during pregnancy with certain
drugs and substances.
The developmental genetics is inseparably linked with science of
embryology. Almostall experimentsin developmental geneticsis confined
to womb ofa mother in which embryo is developing. It is only with the
11
HUMAN GENETICS
help ofembryology that one can identify various tissue types,its structure
and relationship with other tissues. It is only through the embryonic tissue
that wecan identify whether gene isswitched“on ’or“off'. While studying
effect ofmutations and teratogenic agents,it is science ofembryology that
can tell us about the nature ofthe changes undergone during such effects
so thata plausibleexplanation can besoughtforfiom thescience ofgenetics.
4.Pharmacogenetics
Drugs can be used to reveal genetic variations oforganisms e.g.
certain bacteria are resistant to certain antibiotics; certain insects are
resistant to the DDT and organophosphorus insecticides. Human beings,
too, reveal certain variations in response to certain drugs. The term
pharmacogenetics was introduced by Vogel in 1959 for the study of
genetically determined variationsthat are revealed solely by the effects of
drugs.
Once a drug is taken orally,it is broken down into fine particles
and absorbed in the gutfrom where it reaches blood stream.From blood,
it is distributed to most ofthe tissues and tissue fluid.A small part ofit
really reaches the target tissue and the rest is either excreted unchanged or
first metabolized then excreted.In due course,either directly or through
metabolism,all the drug is excreted out.The metabolism ofmany drugs
involves biochemical modifications,usually taking place in liver,during
which the drug is linked to pother molecule,
a.Understood Pathways:Persons vary in the waythey metabolize
the drug and this can be genetically determined. Biochemical steps of
many such metabolism is well worked outand understood.Forexample,
take the case ofisoniazid,an antitubeieulosis drug.The drug is metabolized
by the process ofacetylation which takes place in liver.Persons differ on
the basis ofrate ofinactivation, being rapid or stow inactivators.Take
another example.Succinylcholine is a muscle relaxant.Some persons are
found to be sensitive to therelaxant because ofan abnormal plasmaenzyme
called pseudocholinesterase.Similarly,persons vary in their reaction to
malaria]drug,Primaquine.Some develop haemolytic anaemia(anaemia
due to break down ofRBC)due to deficiency ofthe enzyme glucose6
12
pliosphate dehydrogenase in their RBC.You uill find a few facts about
tliis enz>TTie in biochemical genetics.
Thiopurine drugs are used in treatmentofcertain forms ofCancer.
About 0.3% ofpopulation are unable to properly metabolize the drug
hence develop seriousside effects.Thedeficiency seemsto be ofan enzyme
ofRBC,TMPT(thiopurine methyl transferase)which has genetic basis.
Debrisoquine,a drug used in treatment ofhypertension,is not
metabolized by 5-10% ofBritish subjects.Though initially the subjects
were* supposed to be homozygotes for a recessive gene, recent
observations have revealed at leastfourdifferent mutationsand thattoo in
introns thatresultin faulty mRNA splicings.
Organophosphates are widely used in agriculture and industry.
The enzyme that metabolizesthe substance is paiaoxonase,a product of
two allele polymorphic systems.Some can metabolize the drug faster than
others.
b.Unknown Pathways:Coumarin isan anticoagulantdrug which
is used in treatment ofmyocardial infarction to prevent the blood from
clotting. Some persons require 20 times the usual dose prescribed for
normal patients.In rats,ifhasbeen shown to be due to high levels ofvit K
'Which counteracts the drug.
Malignanthyperpyrexia is irarecomplicadonofanaesthesiaduring
whichmusclesremain rigid whili emperatuie runsas high as 108®F.The
condition seemsto be inherited as i tosomal dominanttrait.Patientsoften
have raised serum level ofcreatine inase and are sensitive to caffeine and
some otherchemicals.The real cause has not been ascertained,though it
seemsthat there is basic defectofreduced uptake and binding ofcalcium
ions to the sarcoplasmic reticulum q1 muscles.
Persons also differ in metabolism ofAlcohol.It is metabolized in
liver byenzymesADH and ALDH(alcohol dehydrogenase and aldehyde
dehydrogenase,respectively).The re is a typical allele,distributed more
commonly in oriental region,ofADH which rapidly forms acetaldehyde,
and resultsin unpleasantsymptoms.In Europeans, anormal alleleofADH
is more prevalent which slowly metabolize alcohol and hence it is not
unpleasant.
13
IIUMANGIfNETICS
This branch ofgcnetics is inseparably linked to pliarmacology.It
is in pharmacology that \ve study molecularstructure ofdrugsand their
target tissue and mechanism,ofaction ofthe drug.>\ên a drug does not
show a predicted mechanism ofaction.it becomes necessaiy to explain
the reasons. It is where pharmacogenetics steps in and analyses the
variations and its probable genetic reasons.
5.Population Genetics:
Evolutionaiy action takes place atthe level ofpopulation.This is
not to deny the fundamental underlying importance of molecular,
chromosomal,cellular or otganismal events.Population geneticsstresses
that evolution operates on groupsoforganisms noton individualsortheir
component parts.
In population genetics,individual genes have no meaning.Itis the
gene pool ofthe population that matters.The gene-pool consistsofall the
genes,in ail their allelic forms,in tl^reproductive gametesofthe peculation.
Changes in the gene pool will reflect changes in the population.The more
rapidly the gene pool shifts,the fasterthe population undergoeschange.
One cannot study the entire gene pool.Even ifone possessed the tool to
identify all ofthe genesofa gene pool the amountofwork would b^me
prohibitive and burdensome. Population genetics, thus, selects a
phenotypically measurable gene-markerand studies its frequency overa
period oftime. Gene frequency ofa given allele is a function ofpercent of
individuals in the population who have that gene and thus its value may
range from zero to 100 percent.Astable gene pool isonein which fiequency
ofan allele remains stable, whatever its value.
Population genetics,thus,considers frequency ofgenes in the
population and studieseffectsofvariousforcessuch as mutation,selection,
drift, migration, non random mating etc. that destabilizes the genetic
equilibrium and thuscausesevolution.Stability ofthe geneticequilibrium
means that population is experiencing no change.In such a population the
relative proportions ofthe different genoty^remain constant from one
generation to another.Tliis is known asthe Hardy-Weinbei^principle
which was putforward independently by an English mathematician,GR
Hardy,and a German physician. W.Weinberg,in 1908.It will be seen
14
that gene and genotype ftequenc>'remains the same ever}'generation if
Hardy-Weinbeig conditions exists.
Theoretical And Practical Values: Study and analysis ofgene
frequency and changes in them havesome theoretical and practical value.
1.They provide insight into mechanism ofevolution,and they
may often reveal evolutionary change in progress.It can reveal where the
population came from in tennsoftaxonomic relationships and where it is
going in terms of adaptive change. Studies of Gene-frequency of
populationsofmany islands have indirated the population ofthe mainland
itcamefrom along with its degree ofvariance.Population genetics,thus,
can reveal roots ofa population, besides estimating its evolutionary
progress.
2.Observablechangesin the frequencyofa gene tliatentail physical
handicaps is often useful for national agencies that are responsible for
anticipating future needs ofa society in terms ofhealth care,educational
programmes,man-power planning etc.
3. By applying rules ofpopulation genetics one can know the
statusofcarriers ofa disease,and by working out the degree ofinbreeding,
the probable percentage of persons affected with certain autosomal
recessive diseases. For example,infrequency ofalkaptonuria is known,
the status ofcarriers in the popula m can be calculated in this way.
AlkaptonuriaafFects about nechild in every 1000000.Therefore.
q2=l/ 000 000
therefor*. i = 1/1000
butp = 1 -q
therefore p“1 -1/1000
= I (api.rox)
The frequency ofcarriers=2pq
= 2.1.1'1000
= 1/500
Thisexamplealso illustratesanother important point,which isthat
mthegeneral population carriersare very much morecommonthan affected
individuals for any autosomal recessive disorder.Ifthe status ofcarriers
15
HUMAN GENETICS
becomes known national agencies can work out number of probable
sufferers in the future and the resources needed to meet such a situation.
4.Population genetics helps not only in discovering “roots’* ofa
population but also “routes'* ofa population.Study ofgene frequencies of
ABO system has provided valuable information regarding the routes of
migration ofpeople in the prehistoric times and has supported results
obtained form anthropological studies and comparative linguistics.
5.Tools and analyses ofpopulation genetics has aided in blasting
away myth ofracial superiority and thus has become important weapons
in ideological war against those who supportracism.No race can claim to
be genetically pure,it is the frequency variations ofdifferent alleles that
make populations appear different. All populations have deleterious
recessive genes hidden from natural selection in heterozygotes and it will
be earned so for a long time transgressing all the political divide.
6.Population genetics raisessome ethical questions too.Should a
haemophiliac transfused with artificially ^thesized factor VIII inoiderto
prolongits life span and reproductive time?People with individual concern
reply in‘Yes*. Would the answerremain same ifwell-being ofpopulation
is concerned?Possessorofsuch recessive deleterious gene will only add
to die genetic burden ofthe population in the long run.Population genetics
does not suggest a way out, though it nonetheless provides with the
.opportunity to calculate cost-benefit ofthe situation.
Methods OfStudy:The discovery ofthe Hardy Weinbeig law
resulted in study on frequencies ofgenetically determined variations.Data
on genotype,or phenotype,or gene-allele,or chromosome structure are
collected from field study or laboratory experiments on a population basis.
The observed number is compared with expected number and the
difference is tested for significance by the chi- square test. It answers the
question that whether something has or has not any effect on difference
between expected and observed frequency.
The population genetics,thus is concerned with describing the
genetic constitution ofthe population. When evolutionary differences
between populations become significant,a study ofchanges in the gene
frequency becomes study ofmicroevolution.
16
Population genetics embraces four fields - anthropological and
.cytological studies for the collection of datas, and mathematical and
statistical formulations for interpretation of these datas in order to
comprehend its significance.
6.Radiation-Genetics
Ionizing radiations include electromagnetic waves ofveiy short
wave lengths such as X-rays and gamma rays,and high-energy particles
such as alpha particles and neutrons.Natural sources ofionising radiation
include cosmic rays and external and internal radiation from naturally
occurring radioactive elements in the environment.Artificial sources of
radiation include those resulting from diagnostic radiological procedures,
radiotherapy,rc:iipational exposure and nuclear accidentsand explosions.
In 1927 H J Muller demonstrated that exposure ofcolonies of
Drosophila to X-rays resulted in an increase in the numberofmutations in
excess ofthose occurring spontaneously.He thusshoweu that X-rays are
mutagenic and for his work in the field ofradiation genetics he wasawarded
the Nobel prize in 1946.Further experimentson Drosophila haveshown
that ionising radiation may cause mutationsin both thesex cells and body
cells. Mutationsinduced in the body cells are termed somatic mutations.It
is with mutations in the sex cells that the geneticist is most concerned
because they can be transmitted to future progeny.
Effects OfRadiation
1.Somatic Effects: Those near the site ofatomic explosion in
Japan in 1945,many w^killîmmediately bythe blastand manysuffered
from the effects ofhaving received an enormous dose ofradiation.Some
died within 10 days,others were ill for several weeks.Those exposed,
lost their hair and their bone marrow activity was greatly reduced so that
the numberofcirculating leucotês wasconsiderably diminished and their
resistance to infection wastherefore severely impaired.Among those who
recovered from the immediate effects,some ofthem later developed
leukaemia.
Thesomaticeffectsofa high dose ofradiation toalocalised volume
.oftissue are local tissue necrosis(radiation bum)and general malaise with
some nausea and vomiting(radiation sickness)
n
HUMAN GENETICS
2.Genetic Effects: Tlic genetic elTects ofradiation are not easy
to assess for they are not manifest in the generation which is exposed to
radiation butin subsequentgenerations.Ifadominant mutation is produced
then it will be manifest in the next generation but a receîve mutation is
only likely to be manifest when two heterozygotes many and have children.
Several lines ofexperiments have been devised to assess genetic effects
ofradiation which includes offspring of: persons exposed to radiation,
persons receivings pelvic radiotherapy,radiologists and nuclear power
.station workers.
Initially it was claimed that radiation affected x-chromosomes in
males,resulting in births ofmale children(XY).However,studies by Kato
(1975)has refuted the claim. Gardener et.al.(1990)have summarised
that though there is no such evidence at present,we will have to be careful
ifchildren ofsuch persons develop any genetic defect later on.It was also
recommended that such persons must not have more than maximum
permissible dose ofradiation.
The International Commission ofRadiological Protection(ICRP)
working in close liason with various agencies ofthe United Nations has
been mainly responsible for defining what isreferred to as the maximum'
permissible dose ofradiation.The commission has fixed 50 mSv/year,
though it varies from country to country,the lowest being ofthose fixed by
UK,15 mSv.To put this into perspective, 1 mSv is roughly50times the
dose received in a single chest X-ray.
The rad(radiation absorbed dose)is a measure ofthe amountof
anyioniring radiation which isactually absorbed byatissueand isequivalent
to 100ergs ofenergy per gram oftissue.A rem(Roentgen equivalent for
man)is a measure ofany radiation in terms ofX-rays and is that absorbed
dose which produces in a given tissue the same biological effect as one
rad ofX-rays.In SI units 100rem is equivalent to 1 sievert(Sv).
7. Ecogcnetics
Though the term is new;first given by Brewerin 1971,the concept
has been an old one.followed much ago in past,and developed in the
.second halfof20th Century by such workers as kettlewell,E.B.Ford,
Sheppard. Dobzhansk>’. Dowrieswiell etc wbo worlced mainly with animal
SYNTHETIC BIOLOGY
The term synthetic biology has been around for more than a
decade and is a mix of multiple facets of science. Synthetic
biology is an interdisciplinary branch ofbiology and engineering
that has included in its forum art and architecture.The subject
combines various fields of biology such as bio-technology,
evolutionary biology, molecular biology, bio-physics, genetic
engineering etc. Mr.Mukund Thattai from the National Centre
for Biological science(NCBS) Bengaluru, Julie Legault, from
Massachusetts Institute of Technology and working at Shristi
Institute of Art Design & Technology, Benguluru ,Mr. Yashas
Sketty from Bengaluru, Drew and Tom Knight, IGEM
(International Genetically Engineered Machine) are some of
the main driving force in the area of synthetic biology in
modem days.
In 2009, Mr. Shetty started experimenting with
synthetic biology and.created synthetic biology circuits where
biological parts of a cell are designed to perform functions
similar to electronic circuits. The new combine has
applications in various fields such as synthetic life, cell
transformations, synthetic genetic pathway, biosensors and
industrial enzymes, to name a few. In synthetic life, artificial
life is created invitro from biomolecules.In cell transformation
living cells are transformed by inserts of new DNA. In
synthetic genetic pathway,the precurabr of anti malarial dmg
artemisinin has been commercially produced by genetically-
engineered E,Coli and yeast. In biosensors, an engineered^
oi^nism(a bacterium)reports about presence of heavy metals
or toxins. Synthetic en:^mes have been created that aim to
improve,.detergents and lactose-free dairy products.
populations.The term ecogenetics or ecological genetics describes the

techfuque ofcombined field and laboratory work.Ecological genetics deals
with the adjustmentand adaptationsofpopulationsto their environment,
.19
HUMAN GENETICS
particular!)'in field ofnutritional ecology and infectious diseases. It is study
ofgenetically determined differences in susceptibility to the action of
physical,chemical and infectious agents in environment.Such differences
in susceptibility may be either unifactorial or multifactorial in causation and
some examples are given in Table.
Tabic 3. : Ecogenetic variations in susceptibility to
environmental agents (After Gardner et.al. 1990)
Environmental agent Genetic susceptibility Disease
UV-Light Fair complexion Skin Cancer

Foods
Fat Hypercholesterolaemia Atherosclerosis
fava beans G6PD deficiency lavism
salt Na-K pump defects Hypertension
milk lactase deficiency lactose intolerance
alcohol atypical ADH alcoholism
Inhalant
Dust a 1-antitrypsin deficiency Emphysema
Smoking ● Enzymatic inducibility lung cancer
Allergens Hypersensitivity asthma
Infections defective immunity ?diabetes mellitus
?spondylitis
Zebra-fish Genetics .
It has been a long journey from Mendel's pea-plant
through Morgan's fruitfly, Mcclintock’s maizes Beadle and
Tatum's Ncurospora, Jacob and Monod's E,coli to the Zebra-
fish! Zebra-fish, Danio rerio is being increasingly utilised in
the study of developmental patterns of vertebrates; It is small,
beautiful, rapidly multiplying fish. It offers the option of
inducing]haploid development. Induction and recovery of
cmbr>'oflic lethal mutations has been easy with the Zebra fish
which so essential for the genetic analysis of the embryonic
development biology and we shall be learning about genetic
control of development through these tiny creatures.
20
GENETIC MATERIAL OF MAN
CHAPTER-2
Human beings, as do other animals, show a programmed

development,a definite pattern ofgrowth arid development.I'he blue
IS
print for this programmed development is contained in the DNA which
important constituent ofchromosomes.DNA functions through mRN A
and synthesizes protein.Thissequence iscardinal pointofmolecular biology,
referred to as central dogma
DNA ► mRNA ^ Protein
The first step is referred to as transcription, the second translation
occur
(in recent years formation of DNA from mRNA has been shown to
by reverse transcriptase e.g. in retroviruses).
The DNA and RNA, the two master molecules of life, are called
nucleic acids. The two nucleic acids are each chemically made up of a
purine or pyrimidine base, a sugar and phosphoric acid. On the basis ol
the kind of sugar (deoxyribose or ribose), the nucleic acids are divided
into two main groups: deoxyribonucleic acid (DNA) and ribonucleic acid
(RNA;. DNA occurs only in the nucleus, where it is the major component
of genes. RNA is found throughout the cell, being especially abundant in
nucleoli and in the cytoplasm. The nucleic acids may be broken down
chemically or enzymatically into nucleotides. Thus a nucleic acid molecule
is made up ofmany nucleotidesjoined to form long chains. Each nucleotide
consists of phosphoric acid, deoxyribose or ribose sugar, and a pyrimidine
or purine base. The purine units are adenine and guanine: the pyrimidines
are cytosine, thymine and uracil. Five kinds ofnucleotides are recognized
oh the basis ofthese purines and pyrimidines: (1) adenine-sugar-phosphate.
(2) guaninc-sugar-phosphate, (3) cytosine-sugar-phosphale. (4) ihymine-
sugar-phosphate. and (5) uracil-sugar-phosphate. The DNA molecule has
the first four of thepc nucleotides, the RNA has the first three and the last
one. Altliough the phosphate-sugar part oftite long chain of nucleotides is
regular, the base attached to the sugar is not always the same, and the
order of these bases is irregular and varies from one section to another of
the nucleic acid molecule.
21
HUMAN GENETICS
Structure OfMolecule(Watson-Crick Model)
In 1953 J D Watson and F.H Crick proposed a model of the
structure ofthe DNA molecule which has been widely accepted. Based
on the information then available about the molecule,such as the x-ray
diffraction studies of M.H.F. Wilkins on the spatial arrangement of
molecules,the nucleotide composition ofvarious DNA molecule and the
ratios ofthe purine and pyrimidine bases,they constructed a model-that
suggested plausible answersto such problemsas(1)how specific directions
are transmitted from one generation to another,(2)how DNA could control
protein synthesis and(3)how the DNA molecule could duplicate itself.
According to this model,the DNA molecule consists oftwo
complementary polynucleotide chains helically wound around a central
axis and cross-linked through specific hydrogen bonding between purine
and pyrimidine bases.In this arrangementthe phosphate and sugar groups
are on the outside ofthe axis:the bases are inside and connected to each
other by hydrogen bonds.For each complete turn ofthe double helix,
there are about 10 nucleotides in each chain. The hydrogen bonding is
such that,atany level where adenine isfound on one chain,thymine appears
on the other chain;and wherever guanine is placed on one chain,cytosine
is its mate on the other chain.It will be noted also that Aand T arejoined
by two hydrogen bonds and Cand G by three bonds. A hydrogen bonding
takes place from the sharing ofa single hydrogen atom by two atoms.
Such bonds^weaker than ordinary chemical bonds.One ofthe atoms
acts as a hydrogen donor and the other as a hydrogen acceptor. Donor
atoms and acceptor atoms are found in each ofthe nitrogenous bases.
The DNA molecule has a diameterofabout20angstrom units(I angstrom
= 1/10,000,000 mm).DNA chains have various lengths, but some are
thought to be at least 200.000 nucleotide pairs long.
Semi Conservative Replication
The Watson-Crick model suggests how a DNA molecule can
replicate itself. Since each chain ofthe double helix is complementary to
the other,each has the information to direct the synthesisofa partner.The
two chains separate or unwind,and each chain then serves as a template
22
to s>nthesizc another chain complementar>'to it. In the new chain free
nucleotides from the surrounding medium are properly assembled and
forni hydrogen bonds with matching nucleotides ofthe original chain.Thai
DNA replication occurs this way is indicated by two kindsofexperiments.
One of these methods is by the use of isotope-labelling, such as
phosphorus’-,by which it is possible to distinguish the mother DNA strand
from the daughter-strand.The second method involves the growing of
bacteria on a culture medium ofheavy nitrogen'*. The DNA ofsuch an
organism had a molecular w'eight 1%greater than DNA ofbacteria grown
on nitrogen''*.
The Composition OfDNA In A Human Cell
There is a remarkable amountofDNA in every cell and it is almost
always the same in every cell. Most normal cells are diploid,that is,they-
contain two sets ofDNA,one derived from the-matemal egg and one
from the paternal sperm:each set(or haploid genome)comprises in humans
about 3,000,000,000 base pairs(3000 Mb).All mammals have haploid
genomes ofabout this size. The haploid genome size characteristic ofa
particular species is sometimes called the C-value.Eggs and sperm are,
ofcouise,haploid;some somatic cells have multiples ofthe diploid amount
ofDNA,and are polyploid. Our genomes are larger than those ofmany
other organisms. Viral genomes are trivial, some no more than a few'
thousand base pairs(kb); bacteria have a few million;Drosophila 100
Mb.But in size ofgenome we do not excel other mammals,ncwis,lungtlsh
or onions.
Experiments have showTi that the DNA sequences in ail the
differenttypes ofcell, fora given species, are essentially the same.In
hybridization experiments.DNA from human brain cell competes elTicicntU'
with DNA from human liver. In principle,this means that the genome of
any cell contains the infomiation needed to make the whole organism.In
practice,it has indeed been possible to produce entire adults from single
cells. With plants,this is easily achieved. Nuclei from rapidly-growing
tissues ofamphibians can be transplanted into the eggs devoid ofnucleus
and it develops in adult.Such nuclear transplantation experiment is not
feasible with mammals.It has been found that human(and most eukaiy'Ote)
23
HUMAN GENETICS
DNA ●●●an be divided into three classes, depending on their abundance in
the genome: satellite DNA, interspersed repeated DNA and single copy
DNA.
Satellite DNA: It consists of short sequences repeated many
times, often in enoimous clusters end to end, (1 Mb long), mostly with, no
known genetic or other function. This makes up about 5% ofthdliuman
genome; each ofthe fourmain human satellite sequences occurs in about
100,000 copies. If the base sequence of such rêated sequence is very
different from that of average DNA then the tandem repeat will have a
different density from the average and in experiments where DNA is
fractionated according to its density, the repeat appears as aminor fraction
distinct from bulk hence refened to as DNA Satellites. DNA Satellites
vary enormously between species. Satellite can be divided into mini and
microsatellite. A function can be attributed to the telomeric minisatellites,
found at the ends ofchromosomes. In which a hexanucleotide sequence
(mostly TTAGGG) is repeated about a thousand times; these play an
important part in DNA synthesis and chromosome integrity. More
importantly, from the point ofhuman medical genetics. Some ofthe other
satellite elements vary considerably between individuals. These are the
hypervariable minisatellites, which occur as about a thousand copies of
variations on the theme GGGCAGGAXG (x any base). Almost as variable
are the microsatellite DNAs, brief lengths of tandem repeats of very
short sequences, most frequently CA or CT or just A. A microsatellite
occurs, on average, about once every 20 kb; (1 kilobase=i000 nucleotide
base pairs). Number ofrepeats in a satellite vary in every individual. Their
variability makes them useful markers in molecular genetics, though most
of them have no direct genetic effect. Collectively, they ai'e sometimes
known as VNTR elements, short for variable number tandem repeats.
Interspersed Repeated DNA: Another highly repetitive form
is interspersed repeated DNA, 300 to few thousand long. This DNA
makes up about 20% of the human genome. Some ofthis is transcribed,
some of it, indeed, consists of elements that are present in many genes.
One human interspersed elernent is HoqAIufamily, (so called because its
members contain cleavage sites for the Alu I restriction enzyme arid
24
GENETIC MATERIALOF MAN
therefore generate characteristic fragments). Members ofthe
are about 300 bp long and occur apparently at random in the genome,
about one every 6Kb making up about 5% of the whole. Some are
transcribed by themselves; most occur inside other transcriptional units,
or are silent. Their function,if,any, is still obscure. Most human genes
contain at least one Alu sequence.In experiments where human DNA is
attempted to be transferred to other cells or vectors,Alu sequences are
useful markers for the presence of human DNA. Other families of
interspersed repeats arc rarer, but their elements can be much longer.
These long interspersed nuclear elements,or LINEs,occur in various
families in mammals,the mostcommon is the LINEl family.Present on
average once every 50 Kb,sometimes also known as the Kpn family,
because they are cleaved by the restriction enzyme Kpn I. Some small
fraction ofthe genome is moderately repetitive DNA.Some are normal
genes that are present in many copies.Their product is needed in large
quantities.They constitute about 10% ofDNA.
Single Copy DNA:The remainder ofthe human genome,about
65% is unique orsingle copy DNA;this comprises mostofthe transcribed
genes. This DNA also contains much untranscribable materials; The
percentage ofDNA that transcribe is roughly estimated to be 20% of
human genome.
Exons And Introns: Even in 20% ofthe transcribable genome
all are nottranslated into protein^ Most human genes,as are all eukaryotic
genes,split into exonsand introns.Exons are translating part ofDNA and
introns existfiinctionless between exons.Introns aretranscribed in mRNA
butare removed during maturation ofmRNA.Apparently,it is only exons
that are functional partofhuman genome.
Euricaiyqticgene
I
I Exon, I Intron Exon^
mRNA l^tbre maturation

|Exon,-Exon^
|
Mature mRNA after remova* flntron
25
HIIMAN GENETICS
Exons can be divided into two groups -
a. House Keeping genes which synthesize proteins required by
every cell.
b.Luxury genes:which synthesize proteins which are specific to
a cell type i.e. cells secreting digestive enzymes, immunoglobulins
hormones,etc.
Packaging OfDNA In Human Cell: Nucleosome
All the DNA,except mitochondria and plastid DNA,are enclosed
in nucleus,surrounded by the nuclei menibrane. Possession ofthis
membrane,with aconsequentdivision ofthe cell into nucleusand cytoplasm,
isthe feature which distinguishes the eukaiyotes-animals,plants,fungi and
protozoa- from bacteria.The nuclear membrane is really two layers with
aspace between the v\ôle being perforated at intervals bycomplex protein
structures,the nuclearpores,which make possible the transportofcertain
important molecules between the nucleus and the surrounding cytoplasm.
Within the inner nuclear membrane there isa network ofprotein fibers,the
lamina. Within this is the DNA,bound to a diversity ofproteins mainly
histones to forYn a complex called chromatin,on account ofits ability to
stain brightly.
Histones are in fact,similar in all eukaryote cells; one type of
histone molecule,called H4,differs in only three amino-acids between
plantsand mammals.Thissimilarity reflects their unvarying structural role.
Histones combine with DNA to form a fundamental unit ofchromatin.
known as the nucleosome.Each nucleosome contains eight histones(two
each ofH2A,H2B,H3 and H4), which together form a protein core
around which DNA is wound intwo turns,forming nucleosome about 11
nm across and 6 nm deep.The DNA thatjoinsthe adjaceiit nucleosomes
is called linker DNA.All the histones are inside the core-protein except
Histone -1 which is present where DNA enters and leaves the core
histones.
These nucleosomes are arranged as regular repeating units: in
electron microscope pictures oflysed nuclei,the nucleosomes are visible
as beads-on-a-string.The string,in thiscase,is the continuous DNA fibre
, that links the nucleosomes^This linker DNA.not being protected by tightly
fK
26
bound core histones,is(unlike nucleosomal DNA)selectively vulnerable
to DNA digesting enzymes such as micrococcal nuclease.Interactions
between H1 histones and nucleosomes allow the formation ofhigher-
order structures. One ofthese is the solenoid,a fiber 30 nm in diameter,
consisting ofa helical arrangementofnucleosomes.Lesscompactstnictures
must also exist in regions where DNA is replicated or transcribed;The
higher-order structures of chromatin are in part determined by the .
interactions with a numerous classofproteins,non-histone proteins.
Most of the time, cells and their nuclei are in what is called
interphase,the period when they make RNA and(ifthQ^ are in dividing
tissues)replicate their DNA.This period ofinterphase is conventionally
divided into three sections:G1,when the cells have not yet replicated their
DNA:S-phase. When they are synthesizing it; and G2 when they have
finished replicating their DNA but have not yet divided.Cells mayspend a
short or a long time in G1 or G2- hours,days or years. S-phase,once
begun,is usually completed in 12-24 hours.The passage between G1,S
and G2 must afiect chromatin structure considerably,butthe differences
are hard to visualize. This constitutes what is called a‘cell-cycle”.
Highest Order OfStructure: Chromosomes

A cell about to divide must have copied its DNA. Each
chromosome,therefore,when it condenres atthe startofmitosis,consists
oftwo identical sisterchromatids:during mitosis,the chromatids separate,
and are distributed between the daughter cells. Before separation, the
chromatids are held closely together at the centipmeris regions ofgreat
structural importance but no genetic content,often rich in satellite DNA.
In human chromosomes,every centromere contains alpha satellite DNA,
long tandem repeats ofa 171-bp sequence, which may be an important
structural feature.The regions outside the centromere,the chromosome
anns,are parallel but less closely apposed.They end in telomeres, which
contain telomeric satellite DNA but no genes.
Three types ofcliromosome can be distinguished,on the basis of.
the position ofthe centromeres: mctacentric where the centromere is
situated at or near the middle part ofthe clu'omosome:acrocentric where
the centromere is closer to one end and telocentric where the centromere
27
HUMAN GENETICS
is near the end ofthe chromatids.The whole set ofthe chromosomes of
one cells is knowias the kaiyotype.The nomial human kaiyo^pe h^46
chromosomes.23from each haploid set.Twoofthese are sex chromosome
called X and Y;females have a pair oflaiê X chromosomes,males have
one X and one smaller Y.
The remaining22pairsare called autosomes.The identification of
the chromosomes was at first bas^simplyon size and shape;it has been
greatly improved by the techniques ofchromosome banding, which
distinguish chromosomes.Certain fluorescent dyes,such as qiiinacrine,
stain some regionsofchromosomes far more strongly than others,so that
with a fluorescence microscope one can see patterns ofbands-called Q-
bands - that characterise individual chromosomes.Later,several other
banding techniques were developed:one ofthe most popular is G-banding,
in which chromosomes are stained with Giemsa dye aftertrypsin digestion
-the resulting pattern can be seen with a normal microscope:G-banding
patterns are the reverse ofQ-banding patterns; Q-bright bands are G-
dark. The number ofbands visible on a mitotic chromosome depends
upon the degree ofcondensation ofthe chromosome.In human cells about
2000 bands can be demonstrated in the least condensed chromosomes:
in the mostcondensed,around 300.Human chromosome number was
believed to be 48.It was in 1956 that Tjio and Levans discovered that it
is 46.It became possible due to improved techniques ofstaining it.
At the Paris Conference in 1971,a standard nomenclature was
agreed for the human kaiy'oQpe and its bands.Autosomes are numbered
in decreasing order ofsize from 1 to 22, X and Y chromosomes are
named separately. Arms are denoted by a letter and number:P for the
shorter arm ofa chromosome(from the French petit, small)q for the
longerarm.Bandsare numbered outwardsfrom the centromere using an
agreed classification ofregions and bands(and sometimes sub-bands)
and are denoted by the appropriate chromosome number and arm letter,
followed by the band number.Thus 13q 14.1 denotes chromosome 13
long arm,region 1, band 4 sub-band 1. Various structural changes in
chromosome is expressed by same method.For exampledel(13q 14.1)
refers the loss ofthe band defined above:a condition which correlates
28
I
GENIITIC MATERIAL OF MAN
with the genetic disease retinoblastoma,(del fordeletion).A wide range
ofchromosomal abnormalities has been described.In deletions a region
of chromosome is missing. Such deletions usually have genetic
consequences.In translocations,part ofone chromosome has been broken
oITand moved to another.Ifa gene happens to lie across the region ofthe
break,it will be destroyed.Fusion oftelomeres ofthe same chromosome
produces ring chromosomes which have serious topological problems in
replication. In isochromosomes centromere divide transversely to produces
two long and two short arms ofthe same chromosome.Another special
case,Robertsonian translocation involvesthejunction oftwo telocentric
chromosomes since there are no genes beyond the centromeres ofsuch
chromosomes. Robertsonian translocations are often innocuous. In
inversions partofa chromosonie has been rotated through 180®.Inversions
are not necessarily harmful but may cause difficulty in the pairing of
homologous chromosomesin meiosis.
Sometimeschromosomes may undergo unequal pairing resulting
in addition ofan extra segment to one ofthe chromosomes.In essence,
chromosomes often undergo structural changes.In man some ofthese
structural changes are associated with syndromes which will be described
at appropriate places.
In addition to these strii *tural changes chromosomes often
undergo numerical changes,called polyploidy.Increase or decrease can
occur in number(Aneuploidy)or b> sets(Euploidy).Increase in number
ofone chromosome make it trisomic; decrease by one number ofone
cliromosome make it monosomic.Such monosomies and trisomics are
often produced among human beings and cause syndromes. Such
syndromes bychromosomal abnormalitiesisdiscussed elsewhere.Euploidy
or doubling ofwhole set ofchromosome is common in plants but rare in
animals and non-existentin human being.
Genetic Code
The kinds ofproteins in a cell determine the structure and function ofthat
cell.All the difTcrent kinds ofchemical transformations for biosynthesis
and for the utilization ofenergy are dependent on enzymes.In all cellular
organisms there arc thou.'ânds ofenzymes,each being a specific protein.
29
HUMAN GENETICS
All ofthem have the siime basic structure-large macromolcculesconsisting
ofpolymers ofsome 20 amino acidsjoined to each other. The highly
specific nature ofenzjrnes can be traced to the unique sequence ofamino
acids and to their three dimensional spatial structure that arises from the
specific foldingsofthe amino acid chain and cross-linkages between certain
pairs of amino acids in adjacent folds. Genes are made up of
deoxyribonucleic acid(DNA).(Certain viruses have RNA in place of
DNA.)Earlierit had been demonstrated thatgenescontrol enemies.Since
amino acids form enzymes(proteins)there must be some connection
between the DNA ofthe gene and the amino acids ofthe proteins.How is
infonnation in the form ofDNA molecules conveyed to sites ofprotein
formation? In other words how are genetic informations translated? The
coding problem indicated that there must be some relation between the
sequence ofthe four bases ofDNA and the sequence ofthe 20 amino
acids ofproteins.The coding hypothesis had to account forthe way these
; four bases(adenine,thymine,cytosine;guanine)mustarrange themselves
so that each permutation is the code for an amino acid. In the coding
procedure it is obvious that there cannot be a 1:1 correlation between
four bases and 20 amino acids because that will code for only4amino
acids.Ifthe coding unit consists of2 bases,only 16 amino acids can be
coded for.
A T C G
A AA AT AC AG
T TA TT TC TG
C CA CT CC CG .
G GA GT GC GG
This also falls short of20amino acid that needed to be coded for.
Therefore,the protein code must consist ofat least three bases
because 64 possible words can be formed by four bases when taken as
triplets. DNA must then be considered a language written in a 4 letter
alphabet. The particular composition or sequence ofamino acids in a
given protein are thus specified by the particularsequence ofamino acids
30
GENETIC MATERIALOF MAN
in a given protein are tlius specified b>'the particularsequence ofnucleotide
pairs in a specific DN A mole^le.The information iscoded in DNA ofthe
nucleus,vîiereas protein sjuthesisoccurs iiithecytoplasm.An intermediaiy'
ofsome kind between the two regions is necessary.This intermediary is
special kind ofRNA called messenger RNA.Messenger RNA is thought
to be transcribed directly from DNA in the nucleus,each ofthe many
messengers RNA being determined by a gene or a particular segmentof
DNA.(RNA differsfrom DNA in havinga sugar residue ofribose instead
ofdeoxyribose).In this process ofmakinga complimentary copy ofone
strand or gene ofDNA in the formation ofmessenger RNA,an enzyme.
RNA polymerase, is needed. The messenger RNA when formed is
separated from the DNA and migrates through nuclear pores into the
cytoplasm of the cell, where it becomes attached to ribosome,
submicroscopic structures ofprotein,and a nonspecific RNA.Here Ae
messenger RNA molecule serves as atemplate against which amino acids
are lined in a sequence according to the coded instructionsin messenger
RNA.Amino acids are either obtained in the food supply or synthesized
by the organism.
Various amino acids are activated and en^miatically attached to a
second type ofRNA called transfer RNA.Each transfer RNA is specific
for a particular amino acid. More tl in one kind oftransfer RNA is found
forcâin amino acids.By stepwise addition,the amino acids are guided
by the coding sequence on transfer RNA,to which they are attached and
arranged in the correct order along messenger RNA to form a Protein
molecule.Each gene codesfor about500amino acids,whichisthe average
of a polypeptide chain, and since the codons are in groups of three
nucleotides,there would be 1500 nucleotide pairs in a single gene.These
figures naturally will vary with the protein or enzyme being coded for.
Operon Concept
The genetic code does notexplain how genesare turned offand
on as their products are needed by the cell.It does notexplain w^y certain
enzymesare not formed when they are not needed.Ifan enzyme-forming
system lacks control,the whole economy ofthe cell would be affected
31
HUMAN GENETICS,
adversely. Cells also require control as they differentiate different amounts
ofthesame enzyme at different times.There must be mechanisms in the
cell for repressifjg the synthesis ofenzymes when these are not needed
and for inducing them when they are needed.
In 1960 the two French scientists. F.Jacob and Monod,proposed
the operon hypothesis or model,for explaining how repressions and
inductions ofprotein synthesis might occur.Although the investigators
worked with bacteria,it seems highly probable that their hypothesis applies
to all living beings.The gist oftheir hypothesis for wiiich thq'were awarded
the Nobel Prize in 1965 may be stated in the following way:
I. Structural Gene: The structural genes direct synthesis of
proteins by forming mRNA.
II. Operator Gene:It is a site that binds repressor or activator
elaborated byregulator gene and thereby determines whether a structural
gene would form mRNA or not Ifa repressor binds to it RNA polymerase
is unable to synthesize mRNA.
III. Regulator Gene:It elaborates regulator proteins such as a
repressible protein or aniictivator protein. Repressible protein inhibits
transcription ofmRNA by RNA polymerase.Activator protein.facilitates
transcription ofmRNa by RNA polymerase.
IV. Promoter Gene: Promoter is the site of binding ofRNA
polymerase to DNA for mRNA transcriptions since promoter operator lie
side by side oroverlap.Binding ofrepressor to operatorphysically interfere
with binding ofRNA polymerase to promoter gene.
Two sites in promoter are highly conserved that facilitate RNA
polymerase binding. These are called consensus sequence. The two
consensus sequences are:
a-10 TATA AT(Pribnow Box): Located-10 bp upstream from
start ofmRNA transcription site. The double straiided DNA open from
here for mRNA transcription.
b-35 TTGACA: Located-35 bp upstream which is RNA
polymerase recognition & binding site.
32
. GENETIC PHENOMENA
CHAPTER-3
GENETIC PHENOMENA
Genetics has developed its own terminology understanding of
which is essential for present day knowledge.These tenns are all important
to the student ofheredity, because they arc essential in understanding the
analyses ofgenetic problems. Whenever a cross involves only one pair of
contrasting characters,it is called a monohybrid; when the cross has two
pairs,it is a dihybrid; when the cross has three pairs, it is a trihybrid; and
when it has more than three pairs,it is a polyhybrid. Characters that show-
in the FI are dominant: those that are hidden are recessive. When a
dominant always shows up in the phenotype it is said to have complete
dominance; w'hen it sometimes fails to manifest itselfit is called incomplete
dominance. When two characters form a contrasting pair,they are called
alleles or allelomorphs. The.term factor that Mendel used so widely is
replaced by gene.A zygote is the union oftwo gametes:\v-hcne\cr the nvo
members of pair ofgenes are alike in a zygote, it is homoz\’gous for that
particular character: when the genes arc unlike for a given character,the
zygote is heteroz>'gous. A hybrid,for instance,is a heterozygote.
Penetrance refers to the percentage frequency with which a gene
manifests phenotypic effects. Ifa dominant gene,or,a recessive gene in a
homozygous state,always produces a detectable effect, it is said to have
complete penetrance. Ifdominant or homozygous recessi\ e genes fail to
show phenot\pic e.xpression in ex-eiy case,it iscalled incomplete or ivduccd
penetrance. The genotype responsible for diabetes mellitus. for instance,
ma}’be present, but the disease does not always occur because ofreduced
penetrance.
The phenotypic variation in the expression ofa gene is known as
expressivity. For instance a heritable allergy may cause more se\ ere
.s>Ttiptoms in one person than in another. Environmental factors may cause
different degrees in the appearance ofa phenotype. Lower temperatures
pennit expression ofthe genes for a black colour!n certain regions ofthe
Siamese cat. Wliat is inherited is a certain genotype,but how it is expressed
phcnotypically is determined by environmental and other factors.
IIUMANGI-NETICS
Linkage Is Location Of Genes On A Chromosome
Genes represent the material bases or chemical entities that are
responsible for the hereditary pattern ofan organism. They belong to
chromosomes and go wherever chromosomes go.By long,patient genetic
experiments,their relative positions(loci)on the chromosomes have been
mapped in many cases. Evidence indicates that they are arranged in linear
order on the chromosome.
Linkage alters the expected mendelian ratios,which are based on
free assortment. Linkage was first discovered in 1906 by Bateson and
Punnett in sweet peas when it was found that sweet peas with purple
flower had elongated pollen grains and those vrith red flower had round
pollen grains. Morgan showed in Drosophila that when a wild type fly
with gray body and long vrings is crossed with a fly bearing two recessive
mutantcharacters ofblack body^d vestigial wings,the dihybrids(FI)all
have gray bodies and long wings.Ifa male ofone ofthe FLsistestcrossed
with a female with a blackbody and vestigial wings,the flies are gary-long
and black vestigial.Ifthere had been free assortment,that isifthe various
characters had been carried on different chromosomes,the expected
olTspring would have been represented by four types offlies: gray-long,
gray-ve.stigial,black-long and black-vestigial. However,in this case gray-
long and black-vestigial had entered the dihybrid crosstogether and stayed
together,or linked.
Crossing Over
Linkage, how'cver, is usually only partial, for it is broken up
frequcntl)- by what is known as crossing over. In this phenomenon the
characters usually separate with a certain frequency.How often two genes
break their linkage,or tlieir percentageofcrossing over,varies with different
genes. In some cases this percentage ofcrossing-over is only 1%or less;
w iih others it may be nearly 50%.
■file greater the distance between any two genes, the more likely
iliey v\ ill separate from each other. This crossing-over thus makes possible
new combinations of linked genes.
Crossing-over makes possible the construction of cli^mosome
maps and proofthat the genes lie in a linear order on the chromosomes.
34
GENIiTIC PHENOMENA
To illustrate how this is done one may take a hypothetical case ofthree
genes(A,B.C)on the same chromosome. In the determination oftheir
comparative linear position on the chromosome,it will first be necessary
to find the crossing-over value between any two ofthese genes.IfA and
B have a crossing-over of2%and B and C of8%,then the crossing -over
percentage between A and C should be either the sum(2 + 8)or the
difference(8-2).Ifit isl0%B lies between A and C;if6%,A is between
B and C. By laborious genetic experiments over many years, the
chromosome maps in Drosophila were worked out in this manner.
The Gene And Mutation
Among the variations thatappearin the makeup ofanimals,there
are both hereditary and nonhereditaiy kinds.Nonhereditary variations
are due to environmental changes such as nutrition,light,heat,and other
factors that operate during the developmentofthe animal.Such fluctuating
variations occur in all animals and are not hereditary. The hereditary
variations are due to changesinthe genesorchromosomes and are referred
to as mutations.Ordinarily,genes are very stable,but they are molecules
and are subject to change under the influence ofmany kinds offactors.
Some changes arise spontaneously,and other can be induced by artificial
agencies.Undoubtedly many more mutations occur than are actually seen,
because mostofthem are recessive and produce visible effects only when
they are homozygous. Mutations happen in both somatic and germinal
tissue,but only the latter ones are transmitted sexually.
Mutations generally effect a single base-pair ofDN A and hence
referred to as point mutations. However,more than one base-pair may be
affected. In such cases it is known as mullisite mutations.Multisite mutations
are equivalent to chromosomal mutation.
A mutation involves a change in the chemical arrangement ofa
gene so that there is a difference in the structure and action ofa gene that
may resultin a new character.In such cases the mutant gene now faithfully
reproduces itselfjust as before.The natural mutation rate, which varies
with different animals,is slow butcan be speeded up aitificially by agents
such as radiation, by tempefature, by certain chemicals,and by other
.i5
HUMAN GliNlITICS
environmental agents. Mutations are called random because they are
unpredictable and because they are unrelated to the needs ofthe orgpism,
but some mutations are favoured by tissue and environmental conditions.
Man\- mutant genes are actually harmful because they may replace adaptive
genes that ha^ e evolved in the long evolution ofthe oiganism.However,a
minorit}’ofmutant genes are advantageous and have great significance in
evolution. Some mutant genes are dominant genetically, but more are
recessive and their effects are masked by normaldomiiuint alleles. Mutation
may be a reversible process,and the difference between the rate ofmutation
ofgene in one direction and its mutation rate in the reserve direction is
called its mutation pressure. Such reverse mutations indicate that true
mutations are not gene losses. Gene mutations may occur in one direction
more frequently than in others,and thus certain mutant alleles are far more
common that others.
Plasmagcncs And Cytoplasmic Inheritance
There is some evidence tliat some genetic variability is the result
ofself-duplicating,hereditary units in the cytoplasm.Such units are called
plasmagcnes and are apparently transmitted only by the cytoplasm.Two
examples ofthis t>pe ofcytoplasmic inheritance are offered by plant plastids
and mitochondria.Both are known to have their own DNA.It is supposed
that during early evolutionary phase of eukaryotes, plastids and
mitochondria existed as free living bacterial entities. They were trapped
by evolving eukaiyote cell and thus lost their independent existence(The
endos>mbiunt h\pothesis).The view is supported by the fact that DNA of
these organelles have only coding region and no non-coding region,like
bacteria. We will see later on that eukaryotic genes are split,characterized
by exons and intervening introns.Exons code for protein,and introns are
apparentl) functionless part ofDNA that separate exons.A gene may
have a few exons and a few introns.
Determination OfSex
Soon after rediscovery'ofMendelism,in 1902 McClung discovered that
in certain bugs males have one chromosome less than the number of
chromosomes in females. It was soon found out that chromosomes ofa
.species can be divided into two groups- autosomes controlling metabolic
36
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no related content on Scribd:
following extracts are taken: There are over ten thousand
Europeans and Americans resident in China. The English head
the list with 4,000; the Americans number 1,325; Germans, 882;
French, 875; Portuguese, 805; Spaniards, 461; Norwegians, 375;
Russians, 116; Italians, 108, etc. There are 669 Japanese.
Twenty-two ports are open to foreign residence, that is to
say, that Europeans are allowed to acquire conditional title
to certain lands, on which they live, govern themselves, and
have special privileges in judicial matters. The ports are
Mengtz, Lung Chow, Pakhoi, King Chow, Lappa, Canton, Kowlon,
Swatow, Amoy, Fuchau, Winchow, Ningpo, Shanghai, Chinkiang,
Wuhu, Kiukiang, Hankow, Ichang, Chungking, Chefoo, Tientsin,
and Niuchwang. It is to be noted that Peking does not appear
on this list, although the embassies and legations are
established there. The Chinese who find themselves under
foreign jurisdiction appear more than contented with the
situation, because, although taxes are high, they are fixed.
Two hundred thousand natives live in the European settlements
of Shanghai. Besides the foreign residents of China, a large
number live in ports that have been ceded to other nations.
For instance, Hongkong comprises in its civil population 4,195
Europeans and Americans. With the troops and sailors, this
number is raised to 8,545. Hongkong is the actual capital of
foreign industry in the far East. More than 3,000 vessels,
with a tonnage of nearly 4,000,000 touch there annually. The
same spirit which caused the development of Singapore,
Colombo, and Hongkong is to be found in the foreign
settlements of the open ports of China."
United States Consular Reports,

October, 1897, page 315.
CHINA: A. D. 1897 (May-June).

Cessions and concessions to England and France.
In May, the Chinese government sanctioned an extension of the

British settlement at Tien-tsin from 65 acres to about 300. In
the next month, it satisfied the complaints of Great Britain
concerning the cession of Kiang-Hung to France (see above: A.
D. 1894-1895, MARCH-JULY), by ceding to that Power the Shan
district of Kokang, about 400 square miles in extent, and
leasing to Great Britain in perpetuity a considerable tract at
the south of the Namwan River. The same treaty opened new
routes to trade across the frontier between Burmah and China,
and admitted British consuls and merchants to two new ports.
At about the same time France secured mining privileges on the
Tonquin frontier and rights for the extension of a railway
into Chinese territory.
CHINA: A. D. 1897 (November).

Germany opens the attack of European Powers on the
integrity of the Chinese Empire.
Seizure of the port of Kiao-Chau.
Concessions obtained as reparation for the murder
of German missionaries.
"Among the recent events that have attracted especial

attention to China is the lease to foreign nations of
important strategic or commercial ports on the coast of the
Empire. While the Portuguese have controlled the island of
Macao, near Canton, since 1537, and the English became owners
of the island of Hongkong, in the same vicinity, by the treaty
of 1842, no other nation had possessions on or near the coast
of China until within a comparatively recent date. One result
of the war between China and Japan was that Japan obtained the
island of Formosa, lying 90 miles off the coast of central
China. By this treaty Japan was also to have certain territory
on the peninsula of Liaotung, which commands from the north
the entrance to the Gulf of Pechili, the gateway to the
capital of China; but on the urgent protest of Russia, France,
and Germany this was abandoned, and the mainland of China up
to that time thus remained intact. On November 4, 1897,
however, the German Government seized the port of Kiao-chau,
on the northeastern coast of China, asserting as the cause of
its action the desire to obtain satisfaction for the murder of
[two] German missionaries by Chinese on November 1 of that
year. This port was held by a German war ship until the
announcement of a treaty with China by which the port of
Kiaochau and adjacent territory were leased to Germany for a
term of ninety-nine years, the German Government being given
the right to land troops, construct fortifications, and
establish a coaling and naval station, while German subjects
were to have the right to construct railways, open mines, and
transact business in the rich mineral and agricultural
province of Shantung, in which Kiaochau is located, Chinese
vessels, however, to have the same privileges in the port of
Kiaochau that the German Government might decide to give to
other nations."
United States Bureau of Statistics,

Monthly Summary of Commerce and Statistics,
March, 1899.
{81}
The terms of the German acquisition of Kiao-chau, as

officially communicated to the Reichstag by Herr von Bülow,
Foreign Secretary of the German Empire, on the 8th of
February, 1898, were as follows: "The Imperial Chinese
Government, in fulfilment of the legitimate wish of the German
Government to possess, in common with other Powers, a point in
the matters [waters?] of Eastern Asia, where German vessels
may be fitted out and repaired, where the necessary materials
can be deposited, and other arrangements made in connection
with that object, cedes to the German Government in the form
of a lease, to run, as at present fixed, for a period of
ninety-nine years, the territory situated on both sides of the
entrance to the Bay of Kiao-chau, in South Shantung, more
accurately described below, in such a manner that the German
Government will be at liberty to erect all necessary
buildings, &c., within the territory, and take all the
measures required for their defence. According to the English
chart of Kiao-chau Bay of 1863, the district leased to the
German Government consists of the following:
1. The promontory north of the entrance to the bay, bounded on

the north-east by a straight line drawn from the extreme
north-eastern point of Potato Island to the sea-coast in the
direction of Zoshan.
2. The promontory south of the entrance to the bay, bounded on

the south-west by a straight line drawn from the southernmost
point of the inlet situated to the south-west of Tschiposan,
in the direction of the Tolosan Islands (Weber chart), to the
sea-coast.
3. The Island of Tschiposan and Potato Island, as well as all

the islands lying at the entrance to the bay, inclusive of
Tolosan and Seslien. Further, the Chinese Government undertake
not to frame any Regulations within a zone of 50 kilometers
round the bay without the consent of the German Government,
and, in particular, to offer no resistance to any measures
necessary for regulating the course of the rivers. The Chinese
Government also grant to German troops the right of passage
across the zone above described. With the object of avoiding
every possibility of collision, the Chinese Government will
exercise no rights of sovereignty within the leased territory
during the period of the lease, but they cede these rights as
well as those over the entire water-surface of the Bay of
Kiao-chau to the German Government. The German Government will
erect sea-marks on the islands and shallows at the entrance to
the bay.
4. In the event of the territory leased not proving to be

adapted to the requirements of the German Government, the
Government of China will cede to Germany a more suitable
district, and will take back the Bay of Kiao-chau, paying
compensation for any improvements or constructions the Germans
may have made there.
5. A more accurate delimitation of the boundaries of the

district leased will take place in accordance with the local
conditions, and will be carried out by Commissioners from both
Governments."
The Foreign Secretary added the following particulars

respecting the area, &c., of the territory and the character
of the lease:
"The territory leased, the boundaries of which are not yet

accurately determined, will cover an area of 30 to 50 square
kilometers. Consequently, it is materially larger than the
British possession at and opposite Hong Kong. For military
reasons, the northern boundary had been pushed a little
further forward than is shown on the map presented to the
Budget Commission. The number of inhabitants is calculated at
a few thousand. As regards the size of the bay, accurate
details are as yet wanting. It runs about 20 geographical
miles into the mainland. At its narrowest point, the entrance
to the bay is about 3,000 metres broad. Two-thirds of the bay
afford harbour accommodation. The rent payable to China, the
exact amount of which has not yet been determined, is an
unimportant point, as it possesses a nominal character merely
representing the continuation in theory of the proprietorship
of China over the territory ceded. The following stipulations
have been secured respecting railway and mining
concessions:—The Chinese Government have consented to hand
over to a German-Chinese Railway Company, to be formed
hereafter, the construction of a railway from Kiao-chau, which
will run first in a northerly and then in a westerly
direction, to be subsequently connected with the projected
great railway system of China. The railway will serve the
coalfields of Weih-sien and Poshan, situated to the north of
Kiao-chau, which will be exploited by German capital. The
Chinese Government have further pledged themselves to accord
to the Railway Company to be thus formed, conditions at least
as favourable as those granted to any other European Chinese
Railway Company in China."
The Foreign Secretary concluded his speech with an exposition

of the motives which had induced the German Government to
occupy Kiao-chau in preference to other places. Its proximity
to the scene of the massacre had been the first consideration.
Secondly, it was favourably situated from a political point of
view, being removed from the French and British spheres in
Southern China and from the Russian base of operations in the
north. Lastly, the spacious, ice-free harbour, the climate,
which is probably the best to be met with in China, and the
existence of coalfields in the vicinity of the coast, offered
sufficient grounds for the choice of Kiao-chau. Herr von
Billow might have quoted in this connection a candid remark
which had been made not long before by the "Kolonial Zeitung:"
"The principal point is that the Power which possesses Kiao-chau
will control the coal supply in northern Chinese waters."
Great Britain, Papers by Command:

China, Number 1, 1898.
CHINA: A. D. 1898 (February).

British diplomacy in China.
The tone in which foreign demands were made
on the Tsung-li Yamên.
Agreement not to alienate the Yang-tsze region.
Early in 1898 the Chinese government was in need of money for

the final payment of indemnity to Japan, and opened
negotiations with the British government for the guarantee of
a loan: Her Majesty's Ministers were quite ready to give the
needed financial aid, for a consideration, requiring, in
return, that Ta-lien-wan should be opened to trade as a treaty
port. But Russia was then scheming to secure possession of
Ta-lien-wan, and interfered with the British negotiation so
vigorously that the Chinese were frightened into breaking it
off, even after they had practically accepted the offered
loan. Not daring, however, to take from Russia the financial
guarantee which they rejected at British hands, they thought
to balance themselves between these jealous rivals by
borrowing without help from either. Both the Powers were thus
offended, England especially showing stern resentment on
account of the slight with which she had been treated. The
following report by Sir Claude MacDonald, the British Minister
at Peking, of his interviews with the Tsung-li-Yamên on the
subject, is very interesting, as showing the tone in which the
European Powers were making demands on the government of China
at that time. The despatch of Sir Claude MacDonald is dated at
Peking, February 20, 1898.
{82}
"Since the 4th of February," he wrote. "I have had four

interviews with the Yamên for the purpose of extracting some
concessions in return for the rejection of the offer of a
guaranteed loan from Great Britain after it had in principle
been accepted. At the first of these, on the 5th February, the
Yamên refused to recognize that we had any claim to
compensation, declaring that the refusal of a Russian as well
as a British guarantee left no ground for complaint. I told
them that this argument might have had some plausibility if
the two offers had been equally advantageous, or if the
Chinese Government had not committed themselves to serious
negotiations with us. The British Government had at China's
own request reluctantly agreed to do her a very exceptional
favour, and the Yamên could not suppose that we should accept
with equanimity a brusque intimation that the Chinese
Government had changed its mind.
"The Yamên abounded in protestations of their readiness at

some future date to give proofs of their gratitude to Great
Britain in the shape of encouragement to commerce, but they
insisted that the loan negotiations must first be dismissed,
and all demands for compensation in connection with them
dropped. I refused to telegraph such a suggestion to your
Lordship, and as after long debate they still refused to bind
themselves by any promises, I reminded them that at an earlier
interview they had asked me whether the action threatened by
Great Britain in the event of their accepting a Russian
guarantee would equally be taken if they borrowed from neither
Power. I could not at the time answer the question, but I
could now tell them that Her Majesty's Government had a right
to feel deeply affronted by what had occurred, and I would not
be answerable for the consequences if they declined to make to
Great Britain even such concessions as they had frequently
admitted to be in China's own interests.
"The Yamên begged me to smooth matters for them, to which I

answered that their present attitude made it impossible for me
to do so. Let them permit me to report that China was ready to
open inland navigation to steamers; to establish Treaty ports
at Nanning and Hsiang T'an; and to give reasonable security to
trade by a pledge against alienation of the Yang-tsze region
to another Power, and the rejection of our loan might be
forgiven. All these were matters within the Yamên's power.
"The Ministers did not deny the feasibility of what I had

asked (except as regarded the opening of Nanning), but
objected to these measures being tacked on to the loan, for if
that were done, Russia would at once demand
counter-concessions for the rejection of her loan, and China
would be placed in a very difficult position. On this they
laid much stress. I said I did not insist on the concessions
being formally announced as made to England in connection with
the loan, and should be prepared to move Her Majesty's
Government to treat them as steps taken spontaneously by
China, but that I absolutely refused to treat the loan account
as settled until I had some definite assurance that these
measures would be carried out within a fixed time. The Yamên
again attempted to persuade me to leave the carrying out of
the measures indicated entirely to the Chinese Government, and
it was only after the usual prolonged argument that they
consented to open internal waters to steam navigation within
four months; to let me know at an early date when they would
open a port in Hunan, and to give me a written guarantee
against the alienation of the Yang-tsze region to a foreign
Power."
After reporting conversation on other matters, the Minister

recounted his action on the subject of the Yang-tsze region,
and on that of the opening of inland waterways to steam
navigation, at an interview with the Tsung-li Yamên on the
9th. "I then produced," he said, "a draft of the note I
intended addressing to them with regard to non-alienation of
the Yang-tsze region. This was accepted with little demur,
with the insertion of the words 'now entirely in China's
possession,' which, as recording an undeniable fact, I agreed
to put in. Copies of the notes subsequently exchanged are
inclosed. I have not thought it necessary to narrate the
arguments by which I supported the demand for this pledge at
both these interviews. My chief ground was that we could not
afford to find one morning that by reason of the murder of a
foreign subject, or the refusal of some demand by a foreign
Power, some place on the Yang-tsze had been seized and was to
be retained on a ninety-nine years' lease. I then handed to
the Ministers the despatch … recording their assurance with
regard to steam navigation of inland waterways. They read it
with attention, and accepted it as satisfactory."
Of the notes thus passed between the British Minister and the
Tsung-li Yamên, that of the former, dated February 9, was as
follows: "Your Highnesses and your Excellencies have more than
once intimated to me that the Chinese Government were aware of
the great importance that has always been attached by Great
Britain to the retention in Chinese possession of the
Yang-tsze region, now entirely hers, as providing security for
the free course and development of trade. I shall be glad to
be in a position to communicate to Her Majesty's Government a
definite assurance that China will never alienate any
territory in the provinces adjoining the Yang-tsze to any
other Power, whether under lease, mortgage, or any other
designation. Such an assurance is in full harmony with the
observations made to me by your Highnesses and your
Excellencies."
On the 11th, the Yamên returned the following reply: "The

Yamên have the honour to acknowledge the receipt of the
British Minister's despatch of the 9th February, stating that
the Yamên had more than once intimated to him that the Chinese
Government were aware of the great importance that has always
been attached by Great Britain to the retention in Chinese
possession of the Yang-tsze region, now entirely hers, as
providing security for the free course and development of
trade. The British Minister would be glad to be in a position
to communicate to Her Majesty's Government a definite
assurance that China would never alienate (any territory) in
the provinces adjoining the Yang-tsze to any other Power,
whether under lease, mortgage, or any other designation.
{83}
The Yamên have to observe that the Yang-tsze region is of the
greatest importance as concerning the whole position (or
interests) of China, and it is out of the question that
territory (in it) should be mortgaged, leased, or ceded to
another Power. Since Her Britannic Majesty's Government has
expressed its interest (or anxiety), it is the duty of the
Yamên to address this note to the British Minister for
communication to his Government."
The despatch recording the Chinese concession of steam

navigation on inland waters was in the following terms: "It
was … with great pleasure that I learnt from your Highnesses
and your Excellencies at a recent interview that the Chinese
Government had determined that wherever the use of native
boats is now by Treaty permitted to foreigners, they shall
equally be permitted to employ steamers or steam-launches,
whether Chinese or foreign-owned, or their own boats, and,
further, that this arrangement would come into effect before
the end of the 4th Chinese moon. I shall have great pleasure
in communicating the Chinese Government's decision to my
Government, for it is an indication that China is prepared to
take every step open to her to increase the volume of trade,
and so add to her resources and the wealth of the people."
Great Britain, Papers by Command:

China, Number 1, 1899, page 13-18.
CHINA: A. D. 1898 (February-December).

The "Battle of Concessions," for railway building and mining.
By summer-time in 1898 the scramble among the Powers for

footholds of territory on the Chinese coast seemed to be
giving way to what Lord Salisbury described as "the battle of
concessions," for the building of railways and the opening of
mines. This newer battle gave his lordship much anxiety. On
the 13th of July he cabled to Sir Claude MacDonald: "It does
not seem that the battle of Concessions is going well for us,
and that the mass of Chinese railways, if they are ever built,
will be in foreign hands is a possibility that we must face.
One evil of this is, that no orders for materials will come to
this country. That we cannot, help. The other evil is, that by
differential rates and privileges the Managers of the railways
may strangle our trade. This we ought to be able to prevent,
by pressing that proper provisions for equal treatment be
inserted in every Concession."
The British Minister at Peking, in reply, dissented warmly

from Lord Salisbury's opinion. "The battle of Concessions is
not, in my opinion," he cabled on the 23d of July, "going
against us. … Up to the present, any concessions granted to
other nationalities are far out-balanced in financial value by
the Shansi and Honan mining and railway concession, with its
possible extensions. I have consistently informed the Chinese
government that, as to differential rates and privileges, we
want none ourselves, and cannot admit that other nationalities
have a claim to them." In due time, as will appear, Sir Claude
was able to furnish very good evidence in support of his
contention that the "battle of concessions" was not going
against Great Britain, by forwarding a list of all the
concessions granted to clamoring capitalists and promoters of
the several nationalities. Meantime, he gave close attention
to the varying fortunes of the battle.
A concession for the Peking-Hankow Railway was the one which

interested the English most. Its line would traverse the rich
and populous provinces of Chi-li, Honan, and Hoa-Pé, and be
connected by another line, for which the Russo-Chinese Bank
held concessions, with the valuable coal-mining basin of
Ping-ting. Early in August, the British found reason to
believe that the pending agreement with a Belgian syndicate
for the building of this road was one that would give control
of it to the Russo-Chinese Bank,—which meant Russian, or
Russian and French control. He promptly remonstrated to the
Yamên, and was assured that the agreement had not yet been
submitted to the throne, and would not be ratified if the
effect were such as he had described. He cabled this assurance
to Lord Salisbury on the 6th of August. On the 13th he had a
very different report to make. "I learnt on the 9th," he says,
"that the Yamên had, under the influence of Li Hung-chang,
abandoned this position [that they would not ratify the
Belgian agreement if its effect was to give control of the
Peking-Hankow line of railway to the Russo-Chinese Bank], and
intended to ratify the agreement immediately. In view of the
urgency of the matter, I addressed a note on the same day to
the Yamên, in which I asked for an interview on the 10th or
11th instant, and informed them that the Chinese text of the
Contract had reached me, warning them at the same time that if
they did not give me another interview before they ratified
the Agreement Her Majesty's Government would look upon their
action as unfriendly, and would probably insist on the same
rights being given to Great Britain in all the provinces
adjoining the Yang-tsze.
"On the evening of the 10th the Yamên answered that they would
appoint a day for an interview when they had received the
Contract, which, they said, had not yet reached Peking for
ratification. On the 11th I replied that I understood from
this communication that they undertook not to ratify until
they had seen me. To this they returned an evasive answer to
the effect that they were all engaged by ceremonies at the
Palace connected with the Emperor's birthday, which would last
some days. I should add that I had already, on the 10th, sent
them a note in which I criticized the Contract in detail,
stating finally that I should have further objections to bring
forward at my interview with them. I now hear on good
authority that the Contract was ratified yesterday, the 12th.
That the ratification has thus been rushed through is
undoubtedly due to the influence of Li Hung-chang, combined
with strong pressure on the part of the Representatives of
Russia, France, and Belgium, and if heavy payment is not
exacted from the Chinese Government for their bad faith, Li
will persuade his colleagues that it is safer to slight
England than any other Power, and any pressure which we may
want to bring to bear in other matters will be without weight.
I therefore think that Her Majesty's Government should insist
either:—
"1. On a written assurance from the Yamên that if British

Syndicates apply for any railway concessions in the Yang-tsze
provinces, they shall be given on the same terms as those
which France, under cover of the Belgian Syndicate, has
received in the Peking-Hankow Contract, and that no mining or
railway concessions will be granted in those provinces unless
they have been previously declined by British Syndicates; or
{84}
"2. On a written assurance that all railways for which British

Syndicates are now in Treaty, that is to say—
(a.) The Shan-hai-Kuan-Niuchwang line;
(b.) The line from Tien-tsin to Chinkiang (the latter, as I
understand, in conjunction with Germans and Americans);
(c.) The line from Shanghae to Nanking with its
continuations and branches;
(d.) The lines in Honan and Shansi should be granted
without any further delay on terms identical with those
contained in the Contract for the Peking-Hankow line. The
latter consist, so far as I can learn, in complete control
over the construction, choice of material, working, and
personnel of the line, together with an Imperial guarantee
for the repayment of the loan.
The second demand seems to me to be preferable on the whole;

it will be impossible to obtain either demand without bringing
great pressure to bear, and I consider that the demand should
be made not as a compensatory concession, but as a punishment
for bad faith."
On the 17th the reply of the British Foreign Office was sent
by Mr. Balfour, as follows:
"With reference to your telegram of the 13th instant, inform

Yamên that they must assent to your proposal Number 2 without
delay, omitting from it the Shankaikuan-Newchwang Railway,
which we must deal with as a separate question. You are
authorized to inform them, if you have any reason to apprehend
that they will delay compliance, that, unless they agree at
once, we shall regard their breach of faith concerning the
Peking-Hankow Railway as an act of deliberate hostility
against this country, and shall act accordingly. After
consultation with the Admiral, you may give them the number of
days or hours you think proper within which to send their
reply. The delay should not be of too long duration. It should
be noted, on face of your demand, that Chingkiang Concession
is for Americans and Germans, if they desire a share, as well
as ourselves. Also make it clear that your ultimatum has
nothing to do with the line to Newchwang."
The tone of these demands made them effectual. On the 4th of

September, Sir Claude MacDonald was able to announce to his
superiors, in London: "At an interview which I had with them
yesterday, the Yamên entered into the following
undertaking:—Within the next few days they will address a
despatch to me, apologising for their action, and consenting
to the construction of the following lines by British
Syndicates:
1. A. line from Shanghae to Nanking with a continuation viâ

Chinkiang to Sui Yang. They said, however, that the latter
route was that followed by the line from Tien-tsin to
Chinkiang, for which they said that a Preliminary Agreement
had been signed between Yung Wing and the Anglo-American
Syndicate; and the continuation in question must be dependent
on the cancellation of that Agreement.
2. A line connecting Hangchow and Soochow with Shanghae, to be

continued if required to Ningpo.
3. A line from Canton to Kowloon.
4. The Peking Syndicate to be entitled to construct a railway

to convey minerals from their mines to the Yang-tsze. The
Yamên have also agreed to send me a Confidential note
embodying a declaration that the terms accorded for the
construction of these lines will not be inferior to those
granted for the construction of any railways in China proper.
The Manchurian lines are excluded from the scope of this
Agreement. I venture to think that this is a satisfactory
settlement. I did not give them an ultimatum, confining myself
to a warning of the grave consequences which would now attend
any failure on their part to keep their word. The fact that
the fleet is concentrating is, of course, known to them."
Before receiving this announcement, Mr. Balfour had cabled, on

the 24th of August:
"Negotiations with Yamên may be facilitated if you informed

them at once that, unless the very moderate terms already
demanded are immediately complied with, we shall, in addition,
require the Concession of another line, on same conditions as
those granted in case of Peking Hankow line of railway, and
that additional demands will be preferred as the result of
further delay. If you think it would conduce to the rapid and
satisfactory termination of the negotiations, you are
authorized to make a communication to them in this sense."
Whether this suggestion was acted upon or not does not appear.
This transaction, connected with the project of a railway from

Peking to Hankow, appears to illustrate, not unfairly, on the
whole, the mode in which speculative concessions were being
wrung from the Chinese government in the busiest year of
oriental speculation, 1898. The outcome of the grand "battle"
was communicated by Sir Claude MacDonald to Lord Charles
Beresford, on the 23d of November, in a full list of the
concessions then granted to British subjects, compared with
the grants to other nationalities. "We do not seem," wrote Sir
Claude, with pardonable complacency, "to have come out second
best. … Not a single bona fide or approximately practical
scheme which has been brought to this Legation has failed to
be put through." The summarized result in railway concessions
was
9 British (2,800 miles);

3 Russian (1,530 miles);
2 German (720 miles);
3 French (420 miles);
1 Belgian (650 miles);
1 American (300 miles).
In detail, the railway and mining concessions were described

in the list as follows:
CHINA:
"Railway and other Concessions obtained by British Companies:
I. Province of Shansi.
The Peking Syndicate have acquired the 'sole right to open and
work coal and iron mines throughout the districts of Yu Hsien
and Ping Ting-chou, and the Prefectures of Lusan Fu, Tsü-chou
Fu, and Ping Yang Fu, and also petroleum, wherever found.'
Under their contract, the Syndicate have also the right to
'construct branch railways to connect with main lines or with
water navigation, to facilitate transport of Shansi coal.'
This has been interpreted officially to include the right of
connecting the mines with Siang-yang in Hupeh, the nearest
head of navigation giving access to the Yang-tsze. This means
a railway of 250 miles. As to the value of this Concession, it
is not amiss to quote the testimony of Baron von Richthofen,
the great authority on the geology of China. He says that, 'in
proportion to its area, Shansi has probably the largest and
most easily workable coalfield of any region on the globe, and
the manufacture of iron is capable of almost unlimited
extension.'
II. Province of Honan.

The Peking Syndicate have also acquired rights similar to
those obtained in Shansi in that part of Honan north of the
Yellow River.
{85}
III. Province of Chihli.

The Hong Kong and Shanghae Bank are financing and controlling
the North China railways from Peking to Tien-tsin, and thence
to Shanhaikuan and Newchwang. The total length of these lines
is about 500 miles, of which 300 miles are completely open to
traffic.
IV. This bank has also acquired a half-interest in the

coal-mines at Nan P'iao, in the Ch'ao-yang district. According
to experts, these mines possess the best and richest coal
seams in North China, and they have the immense advantage of
being close to a line of railway and the sea.
V. Provinces of Chihli and Kiangsu.

The Tsung-li Yamên have undertaken officially that the
construction of the Tien-tsin-Chinkiang line shall be
intrusted to an Anglo-German Syndicate. The British portion of
this Syndicate is represented in China by Messrs. Jardine,
Matheson, and Co., and the Hong Kong and Shanghae Bank. This
will be a trunk line of 600 miles, passing through more
populous country than the Lu-Han Railway (the Belgian line),
with which it is certain to be able to compete successfully.
VI. Province of Kiangsu.

A British Syndicate, represented by Messrs. Jardine, Matheson,
and Co., and the Hong Kong and Shanghae Bank, has obtained the
Concession to finance and construct the Shanghae-Nanking
Railway. There is no more paying district than this for a
railway in China. The length of line will be 170 or 180 miles.
VII. Provinces of Kiangsu, Anhui, and Honan.

The same Syndicate has the right to extend the
Shanghae-Nanking Railway from P'u-k'ou, opposite Nanking, to
Hsin Yang, in Honan, a distance of 270 miles.
VIII. Provinces of Kiangsu and Chekiang.

The same Syndicate has the right to construct a line from
Soochow to Hangchow, with a possible extension to Ningpo. This
line will run through very populous districts for over 200
miles. The last three Concessions all lie within the Yang-tsze
region.
IX. Province of Chêkiang.

The Peking Syndicate have also obtained mining Concessions
similar to the Shansi and Honan in this province.
X. Province of Kwangtung.
The Jardine Syndicate has the right to construct a railway
from Kowloon to Canton. The length of line will be nearly 100
miles.
XI. Provinces of Hupei, Kiangsi, and Kwangtung.

An American Syndicate signed a preliminary Agreement for the
construction of a railway from Hankow to Canton in May last.
Negotiations are now in progress for the amalgamation of this
Concession with Number 10, Kowloon to Canton, and the working
of the whole line from Hankow to Kowloon by an Anglo-American
Company. This will be a trunk line of, approximately, 600
miles long.
XII. Provinces of Yünnan, Kweichow, and Ssuchuan.

The right to extend the Burmah system into China as far as the
Yang-tsze is admitted, and surveys are now in progress. This
involves a possible railway of 700 miles.
See Remarks on French Concessions.
CHINA:
"Concessions other than British. Russian.
The Manchurian Railway Concession dates from 1896. As is well

known, it was obtained as recompense for help given in
securing the retrocession of Liaotung. From Stretensk on the
Shilka, where it leaves the main Siberian line, this railway
will cross the Argun and Hingan Mountains, and reach Kirin viâ
Petuna. The whole length from Stretensk to Vladivostock is
estimated at 1,400 miles, of which about 1,000 will pass
through Chinese territory. The Concession is purely
strategical. The country traversed, though potentially rich,
in great part is, and will be for long, sparsely populated,
and the line cannot, in the near future at any rate, hope to
pay its working expenses.
2. The Port Arthur Agreement of March 1898 arranges for the

conclusion by Russia of a branch from the above line to Port
Arthur or Talienwan. The length of the railway will be about
400 miles. Commercially, this branch is more promising than
the first Concession.
3. The Russo-Chinese Bank has signed a contract for the

construction of a branch line from T'ai-yüan Fu to connect
with the Lu-Han trunk lines near Chêng-tung. Length,
approximately 130 miles. They have, up to date, been unable to
raise money for this line. I think it very possible that it
will eventually be built by an Anglo-Russian Syndicate. I am
trying to arrange this.
"French.—The French possess the right to construct three

lines, but beyond acquiring this right they have done nothing.
1. From Tonquin up the Red River Valley to Yünnan Fu, say 200
miles. The impression in French railway circles is that a
railway through Yünnan will not pay expenses, and if any
serious attempt is made to carry out the extension of the
Tonquin system, it will be merely as a stepping-stone to
Ssü-ch'uan. Yet again, any pretensions that a railway from
Yünnan to the Yang-tsze may have to rank as a commercial
project have been pronounced against by every traveller in
Central China.
2. Langson-Lungchow-Nanning Railway; length, about 100 miles.

(There appears to be an alternative open to the French of
going to Pésé instead of Nanning.) The right to build this

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United States Consular Reports,

CHINA: A. D. 1897 (May-June).

In May, the Chinese government sanctioned an extension of the

CHINA: A. D. 1897 (November).

"Among the recent events that have attracted especial

United States Bureau of Statistics,

The terms of the German acquisition of Kiao-chau, as

1. The promontory north of the entrance to the bay, bounded on

2. The promontory south of the entrance to the bay, bounded on

3. The Island of Tschiposan and Potato Island, as well as all

4. In the event of the territory leased not proving to be

5. A more accurate delimitation of the boundaries of the

The Foreign Secretary added the following particulars

"The territory leased, the boundaries of which are not yet

The Foreign Secretary concluded his speech with an exposition

Great Britain, Papers by Command:

CHINA: A. D. 1898 (February).

Early in 1898 the Chinese government was in need of money for

"Since the 4th of February," he wrote. "I have had four

"The Yamên abounded in protestations of their readiness at

"The Yamên begged me to smooth matters for them, to which I

"The Ministers did not deny the feasibility of what I had

After reporting conversation on other matters, the Minister

On the 11th, the Yamên returned the following reply: "The

The despatch recording the Chinese concession of steam

Great Britain, Papers by Command:

CHINA: A. D. 1898 (February-December).

By summer-time in 1898 the scramble among the Powers for

The British Minister at Peking, in reply, dissented warmly

A concession for the Peking-Hankow Railway was the one which

"1. On a written assurance from the Yamên that if British

"2. On a written assurance that all railways for which British

The second demand seems to me to be preferable on the whole;

"With reference to your telegram of the 13th instant, inform

The tone of these demands made them effectual. On the 4th of

1. A. line from Shanghae to Nanking with a continuation viâ

2. A line connecting Hangchow and Soochow with Shanghae, to be