Cell Signaling/

 Biochemistry & Genetics-II

Biosignalling
 Course Code: SHS.109
 Pre-requisite: 103
 Credit Hours: 3
Lecture by
Dr. Naveed Munir
PhD Biochemistry (GCUF & KCL, UK)
M.Phil, M.Sc Biochemistry (UAF)
B. Sc Med. Lab Technology (UHS)
Member Pakistan Association of Medical Lab scientists (MPAMLS)
REFERENCE TEXT BOOK:
Lippincott’s Illustrated Review of Biochemistry by Pamela C. Champe and Richard A. Harvey Latest Ed.
Essential of Medical Biochemistry, Mushtaq Ahmed, Vol 1
 Mendal’s law of
segregation/Gene Hypothesis
&
Genetics of ABO Blood Group
 Outlines
• General terminology
• Chromosome
• Alleles (Gene)
• Mendel Laws of Inheritance
• Mendel’s Experiments
• Genetics of ABO blood group system
• Formation of Blood groups
• H antigen
• Inheritance of ABO blood groups
 General Terminology
• Genetics: The scientific study of heredity

• Character: heritable feature

• Gene: Sequence of DNA encoded for functional product

• Trait: Each variant for a character

• True-breeding: Plants that self-pollinate all offspring are

the same variety
 General Terminology
• Allele: Pair of genes coding for same trait

• Dominate allele: An allele which is expressed (masks

the other) in the heterozygote & homozygote

• Recessive allele: An allele which is present but remains

unexpressed (masked) in the heterozygote
 General Terminology
• Homozygote – pair of identical alleles for a character

– Homozygous dominant- BB

– Homozygous recessive - bb

• Heterozygote – two different alleles for a character (Bb)

• Wild Type = Most common phenotype
• Mutant phenotype = A product of a change in the DNA
 General Terminology

• Genotype – genetic makeup; combination of alleles

an organism has

• Phenotype – appearance of an organism; the

characteristics determined by the genotype and
environmental influences
 General Terminology
• Monohybrid cross – a cross that tracks the inheritance of a
single character
• P generation – (parental) true-breeding

• F1- (first filial) offspring of P generation

• F2 – (second filial) offspring from F1 cross

 What is chromosome
• Chromosomes are thread-like structures located inside
the nucleus of animal and plant cells.
• Each chromosome is made of protein and a single
molecule of deoxyribonucleic acid (DNA).
• Passed from parents to offspring, DNA contains the
specific instructions that make each type of living
creature unique.
• Carriers of the gene or unit of heredity
 Structure of chromosome

Chromosomes are composed of thin threads called

Chromatin fibers.

Chromatin: In non-dividing eukaryotic cells, the

chromosomal material, chromatin, is amorphous and
appears to be randomly dispersed in certain parts of the
nucleus
 Composition of chromatin
• Chromatin consists of fibers containing protein and
DNA in approximately equal masses, along with a
small amount of RNA.

• The DNA in the chromatin is very tightly associated

with proteins called histones, which package and order
the DNA into structural units called nucleosomes
 Gregor Mendel

-“Father of Genetics” A Monk Priest who performed

research in plant breeding.

-Son of a farmer and grandson of a gardener

-Described the units of inheritance and how they pass from

generation to generation

-He called these units “elementen”

-Without knowledge of DNA or chromosomes

 Alleles “Elementen”
In these experiments, Mendel confirmed that hybrids hide one
expression of a trait, which reappears when hybrids are
crossed

Mendel speculated that gametes contained particulate units or

“elementen”

These are now called alleles

- Versions of the same gene

- Differ in DNA sequence at one or more sites

 Mendel’s Experiments
-Experimented from 1857-1863 on traits in 24,034 plants
-He deduced that consistent ratios of traits in the
offspring indicated that the plants transmitted distinct
units.
-Published his work in 1866
-Not recognized during his lifetime (1884)
-In 1900, three botanists re-discovered laws of
inheritance.
MENDEL’S INITIAL OBSERVATIONS

• Mendel noticed that certain characteristics appeared to be

passed on from parents to offspring, in many species, and
wondered why this was so.

• He also wanted to establish what characteristics were taken

from each parent.
 Why Pea?
 Peas are ideal for probing heredity
 Easy availability
 Easy to grow
 Short generation time
 Self or cross fertilization
 Multiple seed from one flower
 Have many traits that have two easily distinguishable
forms e.g. “Tall” Or “Short”
Mendel's first experiment
Pea plants have several advantages for
genetics.

 Pea plants are available in many varieties with distinct

heritable features (characters) with different variants
(traits).
 Another advantage of peas is that Mendel had strict
control over which plants mated with which.
 Each pea plant has male (stamens) and female
(carpal) sexual organs.
• When Mendel allowed the F1 plants to self-

fertilize, the F2 generation included both

purple-flowered and white-flowered plants.
– The white trait, absent in the F1, reappeared in

the F2.
 Mendel’s experiments

 Worked on seven traits of pea plant

 Each trait with two clear expressions, such as “short”
and “tall”.
 He set up all combinations of possible artificial
pollination, crossed tall with tall, short with short and
tall with short plants.
 Mendel obtained pure lines (true breeding plants)
which he grew for two years to make sure that they
were pure.
 Mendel Studied Transmission of
Seven Traits in the Pea Plant

Figure 4.2
 MENDEL’S GENERALIZATION

1. Alternative versions of genes account for variations in

inherited characters
• - concept of alleles (G=green, g=yellow)
2. For each character, an organism inherits two genes,
one from each parent
– two gametes form somatic cells
– one allele comes from the mother, one from the father
 MENDEL’S GENERALIZATION

3. If the two alleles differ, then:

• Dominant allele is fully expressed in the organism's
appearance (phenotype)
• Recessive allele has no noticeable effect on the organism's
appearance (genotype)

4. The two genes for each character segregate during gamete

production to ensures variation
 Laws of Inheritance
• Law of Segregation: When gametes (sperm, egg,
etc.) are formed each gamete will receive one allele or
the other.

• Law of Independent Assortment: Two or more

alleles will separate independently of each other when
gametes are formed
 Law of Segregation

• The pair of alleles of each parent separate and only

one allele passes from each parent on to an offspring
• Which allele in a parent's pair of alleles is inherited is
a matter of chance
• Segregation of alleles occurs during the process of
gamete formation (meiosis)
• Randomly unite at fertilization
Mendel's First Law – Segregation
 Punnett Square
Represents particular genes in gametes and how
they may combine in offspring

1:3
1:2:1
GENETICS OF ABO BLOOD
GROUP SYSTEM
 GENETIC OF ABO BLOOD GROUP SYSTEM

• Discovered by Karl Landsteiner; locus on chr 9

• Single most important blood group for the selection and
transfusion of blood
• Widely expressed  tissues & body fluids including
Red cells, platelets & endothelial cells
• Three antigens: A, B, H
• Two major antibodies: anti-A and anti-B
 GENETIC OF ABO BLOOD GROUP SYSTEM

• Four phenotypes: A, B, AB, O

• A & B Ag’s autosomal co-dominant (expressed on grp
A, B and AB red cells;
• O phenotype autosomal recessive (most frequent)
 ABO BLOOD GROUP SYSTEM
ABO Antigens
• Present on the surface of red cells as well as tissue and
endothelial cells in the body
• Found in soluble form in plasma & other body secretions
in people known as secretors
• Inherited in simple Mendelian fashion from an
individual’s parents
• 4 possible genes that can be inherited: A, B, O, H
• A and B genes produce a detectable product
• O gene does not produce a detectable product
• H gene is required for A and B antigen formation
 ABO BLOOD GROUP SYSTEM
H Antigen
Required to produce either A or B antigens
• Possible genetic combinations: HH, Hh, or hh
• HH or Hh (+)  produce H Ag  99.99% of
Caucasians
• hh  does not produce H Ag  Bombay
phenotype (Oh)
• Anti-H antibodies rare – found only in individuals
with Bombay phenotype
 ABO BLOOD GROUP SYSTEM

Blood Group Antigen Formation

•A, B and H genes do not directly produce antigens 
produce an enzyme called transferase  attaches a sugar
molecule to the chemical structure of the antigen  sugar
molecule responsible for specificity
• O antigen  no transferase  no antigen produced
• A and B antigens on surface of RBC  protrude from
outermost layer of cell membrane
 Enzymes Encoded by A, B, H Genes

Genes Enzymes
H L-fucosyltransferase
A 3 N-acetyl-D-galactosaminyl trasferase

B 3-D-galactosyl transferase
O None
ABO BLOOD GROUP SYSTEM
ABO BLOOD GROUP SYSTEM
ABO BLOOD GROUP SYSTEM
ABO BLOOD GROUP SYSTEM
 ABO BLOOD GROUP SYSTEM

Example of determining offspring blood types from known

or suspected genotypes:

Genotype parent #1 (AO)

A O
Genotype parent A AA AO
#2 (AB) B AB BO

Phenotypes of possible offspring's: A, AB, B

ABO BLOOD GROUP SYSTEM
INHERITANCE OF ABO BLOOD
GROUP SYSTEM
ABO BLOOD GROUP SYSTEM

Frequencies of ABO Blood Groups:

Blood Group Frequency

O 45%
A 41%
B 10%
AB 4%