Basic concept of human

genetics

Nursing Class
Curriculum – Anat – 2 hr.

• 1. Describe the process of genetic inheritance.

• Mendelian inheritance
• 2. mention the parts and types of human chromosome
• 3. list the chromosomal disorders with example
• 4. list the teratogenic agents .
 Human Genetics

The science which deals with variation and heredity in human

beings.

Clinical Genetics deals with the diagnosis of genetic diseases

and care of patients with genetic disorders.
 Subspecialties of Genetics

1. MEDICAL GENETICS
2. CLINICAL GENETICS
3. CYTOGENETICS.

APPLICATION OF GENETICS :

1. CLINICAL DIAGNOSIS
2. PRENATAL DIAGNOSIS
3. GENE MAPPING
4. CANCER CYTOGENETICS
• Genetic inheritance is a basic principle of
genetics and explains how characteristics are Genetic inheritance
passed from one generation to the next.

•Heredity is the passing of traits through

generations from parents to offspring.

•Hereditary character and traits are

transmitted by the genes of the chromosome .
Gene, DNA, Chromosome
 CHROMOSOME
 A complex of macromolecules found
in cells, consisting of DNA, protein
and RNA.
 A very long piece of DNA
responsible for transmitting genetic
information.
 Deeply stained thread like structure
within nucleus of each animal cell.
 Visualized during metaphase stage of
cell division.
 In Eukaryotes, the uncondensed
DNA is present inside the nucleus
wraped around histones (structural
protein) called as chromatin

 During cell division, the chromatin

condensed to form chromosome.
 Chromatids are a part of
chromosome attached to it with a
centromere.
Euchromatin : Uncoiled portion of
chromosome which is genetically
active.
Heterochromatin : Coiled portion of
chromosome which is genetically
inactive.
Classification of chromosome

Based on the location of

centromere

1. Metacentric : Chromosome having

centromere at the center
2. Submetacentric : Chromosome
having centromere displaced
towards one end .
3. Acrocentic : Chromosome with
centromere far towards one end.
4. Telocentric : Chromosome with
centromere at the end.
 Denver’s classification:
 According to the length of chromosome it is
arranged into 7 groups from A to G in decreasing
length.

 Karyotyping : Process of arranging the

chromosomes in order from the chromosome
spread .
Classification of chromosomes
•Group A: Largest metacentric (1-3)
•Group B: Large submetacentric (4-5)
·Group C: Medium submetacentric (6-12 & X)
·Group D: Large acrocentric (13-15)
·Group E: Moderate size meta &
submetacentric (16-18)
·Group F: Small metacentric (19-20)
·Group G: Small acrocentric (21-22 & Y)
·X: like group C
Y: very short, like a G group
Indications for chromosome analysis
• Multiple congenital abnormalities.
• Unexplained mental retardation.
• Sexual ambiguity.
• Infertility.
• Recurrent miscarriage.
• Still birth.
• Malignancy & chromosome breakage
syndrome
 NORMAL KARYOTYPE

 Human body cells contain 46 chromosomes in 23 pairs : one of each pair inherited
from each parent
 Chromosome pairs 1 – 22 are called somatic or autosomal chromosome .
 The 23rd pair are called sex chromosomes: XX is female, XY is male.
Human female karyotype shown by bright field G-
banding of chromosomes
 DNA AND GENES

 The biological information fundamental to life is encoded

in the molecule of DNA (deoxyribonucleic acid).
 The molecule of DNA is made of two strands (chains).
 Each strand is a chain of NUCLEOTIDES.
 Each nucleotide is formed of three components: A
phosphate group, pentose (5C sugar) and a nitrogen base
(A, G, C, T).
 GENES are specific sequences of nucleotides.

The full sequence of the DNA or all the genes of an organism is called its GENOME.

 The sequence of nuclear DNA is nearly 99.9% identical between any two humans.
 So, a small fraction of DNA sequence is different among individuals that is responsible for the genetically
determined variability among humans.
Total Genes On Chromosome: 723
373 genes in region marked red, 20 are shown

FZD2
AKAP10
ITGB4
KRTHA8 Genes are arranged in linear order on
WD1 chromosomes
SOST
MPP3

MLLT
6
STAT3
BRCA1 breast cancer 1, early onset
GFAP
NRXN4
NSF
NGFR
CACNB1
HOXB9
HTLVR
ABCA5
CDC6
ITGB3
Chromosome 17
source: Human Genome Project
 Each organisms contains 2 copies of a gene (diploid), one maternal and one
paternal.
 The alternative versions of the gene are called ALLELES.

An allele is an alternative form of a gene (one member of a pair) that is

located at a specific position on a specific chromosome.
An organism having a pair of identical alleles is said to
be HOMOZYGOUS.
An organism having a pair of different alleles is said to
be HETEROZYGOUS.
The complete genetic makeup of an organism is the
GENOTYPE.
The physical expression of the genotype or the
observable properties of an individual is the
PHENOTYPE.
 MUTATION

 Mutation : Defined as any change in the nucleotide sequence

arrangement.

Types of Mutation :
1. Genome mutation : Chromosome mis-segregation
2. Chromosome mutation : Chromosome re-arrangement
3. Gene mutation : Base-pair mutation
1. Gamete :
A mature reproductive cell that is specialized for fertilization.
Each Gamate contains haploid set of chromosomes.
2. Cross: Mating between two individuals .
3. Zygote: Cell produced by fusion of male and female gametes.
4. Gene : A segment of DNA responsible for production of one
protein or character.
5. Locus : Location of a gene on a chromosome
6. Alleles : An alternative forms of a gene
 GENETIC TERMINOLOGY :

5. Genotype : Genetic constitution of an organism

6. Phenotype : Physically observable features
7. Dominant : Single copy of mutation that expresses the disease
condition is known as Dominant.
10.Recessive : Requires two copies of mutation to produce disease
11.Co dominance : When two alleles both appear in a phenotype (AB
blood group) .
12.Homozygous : Individual having the same allele in both
homologous chromosomes at that locus.
13.Heterozygous : The individual having different alleles on the
two homologous at that locus .
 Historical background of genetics

Experimented on garden peas and

formulated laws of heredity .

1. Law of inheritance
2. Law of segregation
3. Law of independent assortment

Gregor Mendel
Law of Segregation :
 Every individual contains a pair of alleles for each particular trait
which segregate or separate during cell division so that each gamete
carries only one allele for each gene.
Law of Independent Assortment :
 Separate genes for separate traits are passed independently of one
another from parents to offspring
Law of Dominance :
 Some alleles are dominant while others are recessive; recessive
alleles will always be masked by dominant alleles.
 PUNNET SQUARE
 A diagram used to determine the probability of an offspring's having a
particular genotype.
 It is a tabular summary of every possible combination of one maternal
allele with one paternal allele for each gene being studied in the
cross.
 Classification of Genetic diseases

Classical form of genetic disorder

1.Single gene disorder or Mendelian
2.Chromosomal disorders
3.Multifactorial or Complex disorders
 SINGLE GENE DISORDER :
 Caused by mutation in genes in the nuclear genome .
Types 1:
• Autosomal dominant inheritance :
 Disease observed in multiple generation with no skipped Key –
generation. 1. AA – affected
 Affected child usually have an affected parent. 2. Aa – affected
 Heterozygotes (Aa) are affected. 3. aa – normal
 Two affected parents can produce an unaffected child.
 Two unaffected parents will not have affected child.
 Both sexes equally affected .
Eg: Hutington disease , Marfan’s syndrome , Neurofibromatosis.
 Single Gene Disorders (Mendelian): e.g.

Achondroplasia Marfan syndrome Duchenne Muscular

Dystrophy
Types 2: SINGLE GENE DISORDER :
Key –
• Autosomal recessive inheritance : 1. AA – normal
 Most affected child have 2. Aa – carrier
normal parents . 3. aa – affected
 Two affected parents will
always have affected children. Parents Progeny Phenotypes
 Close relatives who reproduce
are more likely to have affected r/r X R/R All R/r All
children. unaffected unaffected
 Both sexes are affected equally.
 Recessive can skip generation. r/r X r/r All r/r All affected
 The recurrence risk is 1 in 4.
r/r X R/r ½ R/r ½ affected
Eg: Sickle cell anemia, Cystic
fibrosis, Phenylketonuria
• Type 4 - X linked dominant inheritance:
 Males and females are equally affected by dominant conditions as single
disease allele is able to express (heterozygous).
 The severity of disorder may be higher in males and low in female due to
presence of another normal X chromosome.
 Affected fathers pass to All their doughters.
Eg :Vitamin D resistant disorder (Rickets)
• Type 3 - X linked recessive inheritance:
 Mostly found in male population because males are hemizygous for
chromosome that single X expresses the disease in males.
 Skipped generation are seen.
 Affected fathers do not pass to their sons.
 Disease is transferred from mother to son.
Eg: Duchene muscular dystrophy , Hemophilia
2. Chromosomal Aberration/Disorder
• Definition: Abnormalities of chromosome.

• Frequency: 6/1000 live birth

• Major cause of spontaneous abortion, congenital malformations, mental

retardation and malignancies.

• Classified as:
• Numerical
• Structural
• Different Cell lines
 Madan Bhandari Academy of Health Sciences

Polyploidy
Numerical
Aneuploidy
Deletion
Translocation
Chromosomal Structural
Duplication
Aberration
Inversion
Ring Chromosome
Isochromosom
Isochromosome
Mosaicism
Different cell lines
Chimerism
Numerical Chromosomal Aberration
• Variation in Chromosomal number than normal.

• Classified as:
1.Aneuploidy
2.Euploidy or Polyploidy
 2. NUMERICAL CHROMOSOME
ABNORMALITIES :
Ploidy (n) is the number of sets of chromosomes in the nucleus of a cell.

1. Haploid : Eupliod cell that have 23 chromosome (Gamete)

2. Diploid : Somatic cell contaning 46 chromosome
3. Triploid : 69 chromosome
4. Tetraploid : 92 chromosome , rare lethal condition

ANEUPLOIDY : Deviation from euploid number. representing gain

or loss of specific chromosome .
 Monosomy : Loss of chromosome
 Trisomy : Gain of extra chromosome
AUTOSOMAL ANEUPLOIDY :
• All autosomal monosomies does not produce
live birth
• 3 autosomal trisomy result into
live birth .
• Trisomy 21: Down syndrome
Trisomy 18 : Edward syndrome
Trisomy 13 : Patau syndrome

SEX CHROMOSOME ANEUPLOIDY :

Klienfelter syndrome : 47,XXY
Super female (47,XXX)
Turner syndrome : 45 ,XO
 Normal Monosomic Disomic Nullisomic
gametes Gamete Gamete

Fig: Segregation of chromosome during gametogenesis

forming normal and abnormal gametes
Structural Chromosomal Aberration

• Alteration in chromosomal structure.

• Causes:
• reconstitution in unusual combination following chromosomal breakage.
• Improperly lining up of chromosome during meiosis.
• Exposure to clastogens / teratogen.

• Categorized as: Balanced: Unbalanced:

• Balanced 1. Translocation • Deletion
2. Inversion • Duplication
• Unbalanced 3. Insertion • Ring Chromosome
• Isochromosome
Deletion
• Loss of the chromosomal segment.

• Severity depends on size of the deleted segment or the

gene disrupted.

• Types:
•Terminal deletion
•Interstitial deletion

• Eg: - Wolf-Hirschchorn (deletion of 4p)

•Cri-du-chat (deletion of 5p)
•Prader-Willi syndrome (microdeletion of 15q)
•Angelmann syndrome (microdeletion of 15q)
Duplication

• Repetition of the chromosomal

segment.
Ring Chromosome

• Chromosome assumes ring shape.

A B

Fig: A. Formation of Ring chromosome B. Ring

chromosome 9
Isochromosome

• Loss of one arm with duplication of the other.

• Translocation

• Transfer of chromosomal segment.

• Types:
• Intrachromosomal
• Extrachromosomal
• Reciprocal
• Non-reciprocal

Fig: Different types of translocation

Fig: Arrow showing the translocation
between chromosome 9 and 22
Inversion
• Chromosomal segment integrated in reversed manner.
 Madan Bhandari Academy of Health Sciences

Insertion
Chromosomal insertion occurs when a segment of one chromosome is translocated
and inserted into an interstitial region of another.
 3. Multifactorial disorders:
 When there is involvement of more than two factors causing the
disease are known as Multifactorial conditions.
 There may be genetic as well as environmental factors included in
disease progression.
 Eg: Cancer, Congenital heart disease, hypertension, diabetes etc.
 Teratogens
 A teratogen is an environmental agent that can adversely affect
the unborn child, thus producing a birth defect.
 Simply, a teratogens are environmental agents that can produce
fetal abnormalities.

 In ancient times a malformed

birth was often seen as a
prophecy or of mystical
significance.
 Irony, It still can be!
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