Errors and exceptions in

chromosomal inheritance
The changes in the genome involving chromosome parts, whole
chromosome or whole chromosome sets are called chromosome
aberrations

• Chromosome aberrations are of following types:

A. Structural changes in chromosomes
1. Deletion
2. Duplication
3. Inversion
4. Translocation
B. Changes in number of chromosomes
1. Euploidy
2. Aneuploidy
 Structural changes in chromosomes
Deletion:
• It is the loss of a segment of a chromosome
• A deletion of any portion of chromosome is usually lethal to a
diploid organism because it causes genetic imbalance
• The chromosomes with deletions can never revert to normal
condition
• If gametes arise from the cells having a deleted chromosome,
this deletion is transmitted to the next generation
• When an organism heterozygous for a pair of alleles, A and a,
loses small portion of chromosome bearing the dominant
allele, the recessive allele on the other chromosome will
become expressed phenotypically. This is called
pseudodominance
Duplication
It is the occurrence of a segment of a
chromosome in two or more copies per genome
The duplicate regions can be adjacent to each
other or dispersed on the same chromosome
Errors
• Deletions and duplications are likely to occur during meiosis
• Homologous chromatids may break and re-join at incorrect places
during cross over
Inversion
• Inversion involves a rotation of a part of chromosome or a set of genes by
180˚ on its own axis
• It essentially involves occurrence of breakage and reunion
• The net result of inversion is neither a gain nor a loss in a genetic material
but simply a rearrangement of gene sequence
• If the centromere is outside the inversion, then the inversion is said to be
paracentric, whereas inversions spanning the centromere are pericentric
Translocations
• When two non homologous chromosomes
exchange their parts, the resulting
chromosomal rearrangements are
translocations
• Translocations may be reciprocal or non
reciprocal
• In reciprocal translocations, a segment from one
chromosome is exchanged with a segment from
another non homologous chromosome. So, two
translocation chromosomes are generated
simultaneously
• Non reciprocal translocations involves the
transfer of a segment in one direction from one
chromosome to another
Changes in number of chromosomes
• Changes in number of chromosomes occur due to Nondisjunction
• Nondisjunction is the uneven separation of chromosomes during the
process of meiosis I and meiosis II
• If tetrad chromosomes fail to separate properly during Meiosis I or
sister chromatids fail to separate during Meiosis II, one gamete
receives two copies of the same chromosome, another gamete
receives no copy
• Two types:
1. Euploidy
2. Aneuploidy
Euploidy
• Euploidy involves variation in the number of copies of the genome or
complete sets of chromosomes in a cell or an organism
• The number of chromosomes in a basic set is called monoploid (n)
value
• Diploid organisms contain two basic sets of chromosomes (2n)
• However, not all organisms are diploid i.e. they contain more than
two monoploid value or basic set of chromosomes
• Polyploidy is more common in plants than in animals
• Polyploidy is of two types: Autopolyploidy and Allopolyploidy
• Autopolyploidy is the polyploidy condition resulting from the
multiplication of same genome
• In this case, each additional set of chromosome is identical to the
parent species
• Autopolyploid may be triploid (3x), tetraploid (4x), pentaploid (5x),
hexaploidy (6x) etc.
• Polyploids with odd number of chromosomes sets are sterile for
example triploids. The problem lies in pairing at meiosis
• An autotetraploid contains four basic sets of chromosomes and arise
by the doubling of 2x complement to 4x
• This doubling can occur spontaneously but it can also be induced
artificially through the application of chemical agents like colchicine
• Allopolyploidy is a polyploid condition formed by crossing related
species and doubling the chromosomes of the hybrid
• An example of natural allopolyploid is bread wheat, Triticum aestivum
(6x = 42)
Aneuploidy
• Aneuploidy involves changes in chromosome number by additions or
deletions of less than a whole set
• In this case organism gains or loses one or more chromosomes but
not a complete set
• The cause of most aneuploid conditions is nondisjunction during
meiosis or mitosis
• Nondisjunction occurs spontaneously
List of terms to describe aneuploidy

Type Formula
Normal 2n
Monosomic 2n-1
Nullisomic 2n-2
Double monosomic 2n-1-1
Trisomic 2n+1
Tetrasomic 2n+2
Double trisomic 2n+1+1
Aneuploidy in human beings
Down syndrome (47, +21)
• It is usually caused by an extra copy of chromosome 21 (Trisomy 21)
• Characteristics: decreased muscle tone, asymmetrical skull, slanting eyes
and mild to moderate mental retardation
Edward’s syndrome (47, +18)
• Second most common trisomy after Down syndrome
• It is trisomy of chromosome 18
• Characteristics: mental and motor retardation, numerous congenital
anomalies causing serious health problems
• They have a characteristic hand appearance with clenched hands and
overlapping fingers
Patau’s syndrome (47, +13)
• It is a trisomy 13
• Major symptoms are somewhat similar to trisomy 18 but they do not
have the characteristic hand shape
Turner syndrome (45, X)
• Female with retarded sexual development, usually sterile, short
stature, webbing of skin in neck region, cardiovascular abnormalities
and hearing impairment
Klinefelter syndrome (47, XXY)
• Male, subfertile with small testes, developed breasts, feminine
pitched voice, long limbs, knock knees
• They have one extra copy of X chromosome in the cell, therefore,
total of two X chromosomes and one Y chromosome
Mutation and Genetic Disorders
Gene Mutation
• A gene mutation is abrupt inheritable qualitative and quantitative change in
the genetic material of an organism
• Gene are the segment of DNA molecule, so a mutation can be regarded as
change in the DNA sequence which is reflected in the change of sequence of
corresponding RNA or protein molecule
• A change may involve only one base/base pair or more than one base pair of
DNA
• Mutations occur in random manner i.e. they are not directed according to
the requirement of the organism
• Most mutations occur spontaneously by the environment effect, however,
they can be induced in the laboratory either by radiations, physical factors or
chemical mutagens
• Mutation has a significant role to play in the origin of species or evolution
Kinds of Mutations
Classification of mutation according to type of cells
Somatic mutations and Gametic mutations
Somatic mutation: mutations occurring in the non reproductive body cells are
known as somatic mutations.
The genetical and evolutionary consequences of somatic mutations are
insignificant, since only single cells and their daughter cells are involved.
However, if a somatic mutation occurs early during embryonic life, the mutant
cells may constitute a large portion of body cells and the animal body may be
mosaic for different type of cells
Example: unilateral retinoblastoma and heterochromia of iris
Gametic mutations: The mutations occurring in the gamete cells (e.g. sperms
and ova) are called gametic mutations
Such mutations are heritable and of immense genetical significance. The
gametic mutations only form the raw material for the natural selection
Classification of mutations according to the size
Two types: Point mutation and multiple mutation or gross mutations
Point mutation: When heritable alterations occur in a very small segment of DNA
molecule i.e. a single nucleotide or nucleotide pair
The point mutations may occur due to following type of sub-nucleotide change in
DNA and RNA:
1. Deletion mutation: the point mutations which is caused due to loss or deletion
of some portion in triplet codon of a cistron or gene is called deletion mutation
2. Insertion or addition mutation: the point mutations which occur due to addition
of one or more extra nucleotides to a gene or cistron are called insertion
mutation
The mutations which arise from the insertion or deletion of individual nucleotide
and cause the rest of the message of the downstream of the mutation to be read out
of phase are called frameshift mutations. They result in production of incorrect,
hence inactive protein due to which death of the cell may occur.
3. Substitution mutation: A point mutation in which a nucleotide of a
triplet is replaced by another nucleotide is called substitution mutation
It affect only a particular triplet codon
Such an altered code may designate a different amino acid and may
result a protein with a single amino acid substitution
It alter the phenotype of an organism variously and are of great
genetical significance
Substitution mutations can be of two types:
Transition: When a purine base of triplet codon is substituted by
another purine base or a pyrimidine is substituted by another
pyrimidine base then this kind of substitution is called transition
Transversion: It involves the substitution or replacement of a purine
with a pyrimidine or vice versa then this type of substation mutations
are called as transversion
Multiple mutation or gross mutations: When changes involve more
than one nucleotide pair or entire gene, then such mutations are called
gross mutations. The gross mutations occur due to rearrangement of
genes within genome
The movement/rearrangement of gene may take place due to following
method:
Translocation: movement of gene may take place to a non homologous
chromosome
Inversion: movement of gene within same chromosome
Classification of mutation according to origin
Two types: Spontaneous mutations and induced mutations
Spontaneous mutations: occur suddenly in the nature and their origin is
unknown
Induced mutations: Besides naturally occurring spontaneous mutations, the
mutations can be induced artificially in the living organisms by exposing them
to abnormal environment such as radiation, certain physical conditions
(temperature) and chemicals. The substances or agents which induce artificial
mutations are called mutagens or mutagenic agents
Mutagenic agents
• The substances or agents which induce artificial mutations are called mutagens or
mutagenic agents
• These are of following types:
1. Radiations:
Ionizing radiations: X-rays, and gamma rays, alpha and beta rays, electrons, neutrons
and other fast moving particles
Ionizing radiations cause breaks in poly sugar phosphate backbone of DNA and thus
causing chromosomal mutations such as break, deletion, addition, inversion and
translocation
Non ionizing radiations: Ultraviolet rays
UV rays induce dimerization on DNA molecules. UV rays form chemical bonds
between two adjacent pyrimidine molecules particularly between two thymine
residues, which displace their positions in DNA helix and they can no longer form
hydrogen bonds with opposing purines and helix becomes distorted
2. Temperature: the rate of mutation is increased due to increase in
temperature

3. Chemical mutagens: affects the chromosomal DNA by following ways:

Direct gene change: Certain chemical mutagens affect DNA directly and affect
the constituents of DNA only when DNA is not replicating
Example: Nitrous acid converts adenine into hypoxanthine and cytosine to
uracil by deamination
Other chemical mutagens include: formaldehyde, methyl and ethyl
methanesulphonate (MMS and EMS), dimethyl and diethyl sulphonate, etc.
Copy error: Certain chemical compounds called base analogues closely
resemble with certain DNA bases and therefore, act as mutagens. During DNA
replication, they are incorporated by DNA in place of normal DNA bases
Example: 5-bromouracil, 2-aminopurine
Genetic disorders
Sickle Cell anaemia:
Sickle cell disease is a disorder that affects the red blood cells, which use a
protein called hemoglobin to transport oxygen from the lungs to the rest of the
body
Normally, red blood cells are round and flexible so they can travel freely
through the narrow blood vessels.
The hemoglobin molecule has two parts: an alpha and a beta
Patients with sickle cell disease have a mutation in a gene on chromosome
11 that codes for the beta subunit of the hemoglobin protein
As a result, hemoglobin molecules don't form properly, causing red blood
cells to be rigid and have a concave shape (like a sickle)
• The sickle-cell disease occurs when the 6th amino acid, glutamic acid of
the beta chain, is replaced by valine to change its structure and function.
• Mutation is a single nucleotide substitution on chromosome 11
• GAG GTG results in substitution of valine (negatively charged) for
glutamate (non polar)
• Sickle cells are stiff and sticky. They tend to block blood flow in the blood
vessels of the limbs and organs. And therefore can cause pain and organ
damage.
• The sickle-shaped red blood cells break apart easily causing anemia
• Hemoglobin S with this mutation is referred to as HbS as opposed to the
normal adult HbA
BETA THALASSEMIA
• Beta thalassemia is a genetic blood disorder that reduces the
production of hemoglobin
• Specifically, it is characterized by a genetic deficiency in the
synthesis of beta- globin chains
• Beta-globin is a component (subunit) of hemoglobin
• Beta thalassemia is caused by a deficiency of Beta globin
inherited in an autosomal recessive pattern, which means both
copies of the HBB(Hemoglobin beta) gene in each cell have
mutations.
• The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they
typically do not show signs and symptoms of the condition.
• A lack of beta-globin leads to a reduced amount of functional
hemoglobin. Without sufficient hemoglobin, red blood cells do
not develop normally, causing a shortage of mature red blood
cells
• The low number of mature red blood cells leads to anemia and
other associated health problems in people with beta
thalassemia.
Progeria
• This is also known as Hutchinson-Gilford Progeria Syndrome
(HGPS)
• Progeria is an extremely rare, fatal genetic condition that affects
children and gives them an appearance of accelerated aging
• It result from a gene mutation arising around the time of
conception or shortly thereafter
Mutations in the LMNA gene cause Hutchinson-Gilford progeria
syndrome
LMNA gene is located on chromosome 1q22 and is composed of 12
exons
Lamin A is an inner nuclear membrane protein with both structural and
cell signaling effects
The single C to T transition at nucleotide 1824 of LMNA does not
change the translated amino acid (Gly608Gly), but activates a cryptic
splice site, resulting in the deletion of 150 base pairs in the 3’ portion of
exon 11
Translation followed by post-translational processing of this altered
mRNA produces a shortened abnormal prelamin A protein with a 50
amino-acid deletion