GENETICS

INTRODUCTION

The term, genetics (gene stands for “to become”), first coined by
Bateson in 1906, it is branch of biologic science that deals with the
transmission of characters from parents to off springs.

Importance of genetics

֎ It helps in understanding of etiology of disease.

֎ It helps to understand variations between normal and
abnormal individuals.
֎ It prevents genetic disorders through prenatal diagnosis
and genetic counselling.
֎ It helps treatment of certain genetic disorders through
correction or replacement of the defective gene (genetic
engineering).

History of Genetics

Gregor Mendel Australian monk introduced a new theory

of inheritance. He believed that heredity is the rule of discrete
units of inheritance. Inheritance of these trait depends on
passing on the trait. For a given trait, individual inheritance of
one gene from each parent is required , thus pairing of two
genes. It the two allele that form a pair are identical it is
homozygous, if two genes are different then individual is
heterozygous.

Gene

Gene is the fundamental unit of heredity . It is a segment of

DNA molecule which codes for a polypeptide. Each human is
estimated to have approximately 30,000 genes. Alterations in
 these genes, or combinations of them can produce genetic
disorders.

Chromosome and cell division

The word “chromosome” is derived from the Greek words for

“colored body”. Human cells contain 46 chromosomes
comprising 22 pairs of autosomes from 1 to 22 and a pair of sex
chromosomes (two X chromosomes in females and one X and
one Y in males).
Each chromosome contain a centromere. Each chromosome is
made up of a short “p” arm and the longer “q” arm joined at the
centromere. The study of chromosomes is referred to as
cytogenetics

Human cell zygote at the time of conception consists of a single

cell. Through rapid division if form a mature human adult.
Human adult consists of approximately one hundred trillion
(1014) cells. This process of cell division is called mitosis.

Mitosis

During mitosis each chromosome divides into two daughter

chromosomes . Mitosis is a continuous process lasting for 1–2
hours. It is divided into five distinct stages: (1) prophase, (2)
prometaphase, (3) metaphase, (4) anaphase and (5) telophase

Meiosis

Meiosis is a specialized cell division process in which a diploid

cell gives rise to haploid gametes. This occurs only in the final
division of gametogenesis. In contrast to mitosis, meiosis occurs as
two rounds of cell division (meiosis I and meiosis II)

DNA
 Deoxyribonucleic acid (DNA) is the hereditary material which is
present in the nucleus of the cell. The DNA is packaged into 23
pairs of chromosomes in each cell.

Nucleic acid

Nucleic acid is composed of a long polymer of individual

molecules called nucleotides. Each nucleotide is composed of a
nitrogenous base, a sugar molecule and, a phosphate molecule.
Nitrogenous base has 2 parts:
(1) purines (adenine and guanine) and
(2) pyrimidines (cytosine, thymine and uracil).

In chromosones genes are linearly arranged in particular

position . They are the hereditary material that code for the
“characters”
Each gene is made up of deoxyribonucleic acid (DNA) in which
genetic information lies. It looks like a rope-ladder , in which
ropes are made up of alternating deoxyribose and phosphate
molecules and each rung consisting of guanine, cystosine,
adenine and thymidine. The whole structure is twisted into a
double helix.

Dominant gene : In this, one member of the pair of gene express .

The gene which express is termed as dominant gene. (Rr)
Recessive gene : the genes which fails to express is termed as
recessive

Phenotype means physical appearance or outward expression of

individual is called as phenotype
Genotype : the underlying genetic constitution is called genotype..

Genetic disorders
 These disorders are classified into the following major groups:

1. Chromosomal disorders: Entire chromosome or segments

may be missing or duplicated or altered.
Examples: Down syndrome (DS), Turner syndrome

2. Single gene disorders (also known as monogenic disorders):

Disorders in which single genes are altered . they are called
“Mendelian” conditions. they follow, Mendelian mode of
inheritance.
Examples: Thalassemia, Spinal muscular atrophy, Hemophilia

3. Mitochondrial disorders: A relatively small number of

diseases are caused by alterations in the small cytoplasmic
mitochondrial DNA and are inherited in non-Mendelian fashion.

4. Multifactorial disorders: Results from a combination of

multiple genetic and environmental causes.

Examples: Birth defects like cleft palate/cleft lip, neural tube

defect, and common diseases like diabetes, psychiatric illnesses
and hypertension

5. Somatic cell genetic disorders: Cancers are caused by additive

effects of mutations in several genes in a somatic cell. Other
disorders included in this group are autoimmune disorders and
aging process

Chromosome Abnormalities
 The chromosome abnormalities can be divided into two numerical
or structural.

1. Numerical abnormalities
a. Aneuploidy : it involve the loss or gain of one or more
chromosome, referred as aneuploidy.
Eg: In trisomy a single extra chromosome is present
(DStrisomy21) whereas in monosomy there is a loss of one
chromosome (Turner syndrome-monosomy X).

b. Polyploidy : The addition of complete haploid set of

chromosomes is called polyploidy.
Eg: In Klinefelter syndrome (XXY), there is an extra X. In
Turner syndrome (XO), an X chromosome is missing.

2. Structural chromosomal abnormalities include

a) Deletions
b) Translocation – robertsonian and reciprocal translocation
c) inversions
d) insertions

1. Deletions
It means loss of part of a chromosome results in
monosomy for that segment of the chromosome
Eg : Wolf-Hirschhorn syndrome (partial monosomy involving
short arm of chromosome 4). Cri du chat syndrome (partial
monosomy involving short arm of chromosome 5)

2. Robertsonian translocation :
In this breakage of two acrocentric (close to centromere )
chromosome (13, 14, 15, 21 and 22) with fusion of their long
arms
a. eg: Down syndrome due to translocation between
chromosomes 14 and 21
 3. Reciprocal Translocation : This involve breakage of at least two
chromosomes with exchange of the fragments
Eg. translocation involving chromosomes 9 and 22

4. Insertion: An insertion occurs when segment of one

chromosome become inserted into another chromosome

5. Inversion: An inversion is a two break rearrangement involving

a single chromosome in which a segment is reversed in position,
i.e. inverted
Inversion can be pericentric inversion (involving centromere) or
paracentric inversion (only one arm of the chromosome)

Multifactorial Disorders
Multifactorial disorders is due to combination of environmental
factors.
Eg: diseaseslike diabetes mellitus, hypertension, obesity and
schizophrenia, etc . congenital malformation like neural tube defect
and congenital heart disease (CHD).

Mendelian inheritance
There are four types
1. Autosomal Dominant
2. Autosomal Recessive
3. X Linked Recessive
4. X Linked Dominant

Autosomal Dominant
  Autosomal dominant (AD) disorders are those in which both
heterozygous and homozygous individuals show the
abnormal phenotype
 Disease is transmitted from one generation to the other.
 One copy of the mutant gene is sufficient for expression of
the abnormal phenotype.
 Multiple generations in a family are affected
 Males and females are both affected in equal proportions
 Males and females can both be responsible for transmission
Examples:
a. Neurofibromatosis (NF)
b. Tuberous sclerosis (TS)
c. Marfan syndrome
d. Familial hypercholesterolemia

Autosomal Recessive
 The disease will be manifested only when gene is present in
homozygous state.
 Manifestations are seen in both male and female of unaffected
individuals.
 The autosomal recessive disorders usually manifest in the
siblings and there is no affected individual in generations above
and below.
• Both males and females are affected
• The parents may be consanguineous
 Examples:
a. Thalassemia
b. Spinal muscular atrophy
c. Mucopolysaccharidosis

X linked recessive
  Affected males transmit the trait to daughters only
 Males are affected and females are carriers
 No male to male transmission
 50% of the sons of the carrier females are affected; 50% of the
daughters are carriers
 All daughters of affected male are carriers
 Affected individuals are related through transmitting (carrier)
female
 It is an Oblique transmission
 A significant proportion of isolated cases are due to new
mutations (some affected males do not reproduce)
o Examples: Hemophilia, Duchenne muscular dystrophy
(DMD), Hunter syndrome

X-linked dominant inheritance

 Looks like Autosomal Dominant

• Daughters of affected male always inherit the disorder
• More females are affected, but have milder phenotype
• No male-to-male transmission
• Affected males with normal mates have no affected sons
and no normal daughters
o Examples:
o Familial hypophosphatasia, Rett syndrome

CLASSIFICATION BASED ON PATHOGENESIS

Based on the pathogenesis birth defects can be classified as
following:
• Malformation: Early embryological developmental error
(e.g. Cleft palate)
• Deformation: Internal or external mechanical forces
alters normally forming structure (e.g. Club foot)
• Disruption: Breakdown of a previously normal tissue
(e.g. Amniotic band sequence)
 • Dysplasia: Abnormal cellular organization within a tissue
resulting in structural changes of organs containing the
tissue involved (e.g. Achondroplasia).

Conclusion
This chapter deals with basic concepts of genetics and genetic
disorders .