chromosomal abrerations

7/30/2019 Chromosomal Abrerations

1/34

VARIATION IN STRUTURE OF

CHROMOSOME

Chromosomal Aberrations


2/34


The somatic (2n) and gametic (n) chromosome

numbers of a species ordinarily remain constant.

This is due to the extremely precise mitotic and meioticcell division.

Somatic cells of a diploid species contain two copies ofeach chromosome, which are called homologouschromosome.

Their gametes, therefore contain only one copy of each

chromosome, that is they contain one chromosomecomplement or genome.

Each chromosome of a genome contains a definitenumbers and kinds of genes, which are arranged in a

definite sequence.


3/34


Variation in chromosomal number or structure

do arise in nature, sometime due to mutation or

spontaneous (without any known causal factors).

Numerical Structural


4/34

Structural Chromosomal Aberrations

Chromosome structure variations result from

chromosome breakage.

Broken chromosomes tend to re-join; if there is more

than one break, rejoining occurs at random and not

necessarily with the correct ends.

Chromosome breakage is caused byX-rays, various

chemicals, and can also occur spontaneously.


5/34

There are four common type of structuralaberrations:

1. Deletion or Deficiency

2. Duplication or Repeat

3. Inversion

4. Translocation.


6/34

Consider a normal chromosome with genes inalphabetical order: a b c d e f g h i

1. Deletion: part of the chromosome has beenremoved: a b c d e fg h i a b c g h i

2. Dupliction: part of the chromosome is duplicated:a b c d e fd e fg h i

3. Inversion: part of the chromosome has been re-inserted in reverse order: a b c f e d g h i


7/34

4. translocation: parts of two non-homologous

chromosomes are joined:If one normal chromosome is a b c d e f g h i

and the other chromosome is u v w x y z,

then a translocation between them would bea b c d e fx y z and u v wg h i.


8/34


9/34

Deletion or deficiency

Loss of a chromosome segment is known as deletion or

deficiencyIt can be terminal deletion or interstitial deletion.

A single break near the end of the chromosome would beexpected to result in terminal deficiency.

Terminal deficiencies might seem less complicated.

But majority of deficiencies detected are intercalary type within

the chromosome.Deletion was the first structural aberration detected by Bridgesin 1917 from his genetic studies on X chromosome ofDrosophila.


10/34

Deletion - deficiency


11/34

A B C D E F

A B E F

WT

deletionX

a b c d e f

a b c d e f

F1:

A B C D E F All WT

a b c d e f

A B E F

a b c d e f

Mutant phenotype for c and

d

(c & d phenotype uncovered

by deletion)

&

50%

50%

Deletion Mapping

In some cases can also map cytologically


12/34

Deletion generally produce strikinggenetic and

physiological effects.

When homozygous, most deletions are lethal, becausemost genes are necessary for life and a homozygous

deletion would have zero copies of some genes.

When heterozygous, the genes on the normal

homologue are hemizygous: there is only 1 copy of

those genes.

Crossing over is absent in deleted region of a

chromosome since this region is present in only onecopy in deletion heterozygotes.

In Drosophila, several deficiencies induced the mutants

.


13/34


14/34

1 2 3

1 2 3

7

7

4 65

deletionloop

Normal chromosome

Deletion chromosome


15/34

Cri-du-chat (Cat cry syndrome):

The name of the syndrome came from a catlike

mewing cry from small weak infants with the disorder.Other characteristics are microcephaly (small head),

broad face and saddle nose, physical and mental

retardation.Cri-du-chat patients die in infancy or early childhood.

The chromosome deficiency is in the short arm of

chromosome 5 .


16/34

Duplication

The presence of an additional chromosome

segment, as compared to that normally

present in a nucleus.

In a diploid organism, presence of a

chromosome segment in more than twocopies per nucleus is called duplication.

T f d li i


17/34

1- Tandem or repeat duplications

l 2 3 43 4 5 6

7 8 9

2- Reverse tandem duplication 1 2 3 4 4 3 5 6

7 8 9

3- Displaced duplications:

(a) Displaced-same arm 123 4 5 623

7 8 9

(b) displaced-different arm 1 2 3 4 5 6 237 8 9

(c) displaced-different chromosome

10 11 3 4 12

Types of duplications:


18/34

Origin

Origin of duplication involves chromosomebreakage and reunion of chromosome segmentwith its homologous chromosome.

Another phenomenon, known as unequal crossing

over, also leads to exactly the same consequencesfor small chromosome segments.

For e.g., duplication of the band 16A of X

chromosome ofDrosophila produces Bar eye.This duplication is believed to originate due to

unequal crossing over between the two normal Xchromosomes of female.


19/34


20/34


21/34


22/34

Inversion When a segment of chromosome is oriented in the reverse

direction, such segment said to be inverted and the phenomenon

is termed as inversion. Inversion occur when parts of chromosomes become detached ,

turn through 1800 and are reinserted in such a way that the genesare in reversed order.

For example, a certain segment may be broken in two places, andthe breaks may be in close proximity because of chance loop inthe chromosome.

When they rejoin, the wrong ends may become connected.

The part on one side of the loop connects with broken enddifferent from the one with which it was formerly connected.

This leaves the other two broken ends to become attached.

The part within the loop thus becomes turned around or inverted.


23/34

Inversion may be classified into two types:

Pericentric - include the centromere

Paracentric - do not include the centromere


24/34

Paracentric Inversions

ParacentricInversions

Chiasmata formation in InversionsThe frequency with which such inversion c.o. takes place depends upon:

The length of the inverted segment. Its location in the chromosome The c.o. characteristics of the individual.


25/34

Translocation

Integration of a chromosome segment into anonhomologous chromosome is known as

translocation.

Three types:1. simple translocation

2. shift

3. reciprocal translocation.


26/34

PACHYT

ENE

METAPHAS

E I


27/34

Simple translocation: In this case, terminalsegment of a chromosome is integrated at one

end of a non-homologous region. Simpletranslocations are rather rare.

Shift: In shift, an internal segment of achromosome is integratedwithin a non-

homologous chromosome. Such translocationsare known in the populations ofDrosophila,Neurosporaetc.

Reciprocal translocation: It is produced whentwo non-homologous chromosomes exchangesegmentsi.e., segments reciprocallytransferred.

Translocation of this type is most common


28/34

Variation in chromosome number

Organism with one complete set of chromosomesis said to be euploid (applies to haploid and diploidorganisms).

Aneuploidy - variation in the number of individualchromosomes (not the total number of sets ofchromosomes).

The discovery of aneuploidy dates back to 1916when Bridges discovered XO male and XXYfemale Drosophila, which had 7 and 9

chromosomes respectively, instead of normal 8.


29/34

Auto polyploidyAllo polyploidy


30/34

Nullisomy - loss of one

homologous chromosome

pair. (e.g., Oat )(2n-2)

Monosomyloss of a

single chromosome (2n-1)(Maize).

Trisomy - one extra

chromosome. (Datura) (2n+1)

Tetrasomy - one extrachromosome pair.(2n+2)

More about Aneuploidy


31/34

Trisomy in Humans

Down SyndromeThe best known and most common

chromosome related syndrome.

Formerly known as Mongolism One child in every 800-1000 births has Down

syndrome

250,000 in US has Down syndrome.

The cost and maintaining Down syndrome case inUS is estimated at $ 1 billion per year.

Down syndrome results if the extra chromosome

is number 21


32/34

Trisomics in human-In chrom. 21 and it causes mongolism which results from the

translocation in the oogenesis .

-

Some abnormalities in man are due to non-disjunction in the 1st

or 2nd meiotic division of the sex chromosomes.

Non-disjunction in 1st meiotic division :

-In mother :

OxxOva

Sperms

xo

Turners (45)

xxx

Triple X Syndrome-Super females- (47)

x

yo

non-viable (45)

xxy

Kleinefelter (47)Y


33/34

In father

O

Xy

Sperms

Ova

Xo

Turners

xxy

Kleinefelter

x


34/34

Non disjunction in the 2nd meiotic division:

In mother :

xx x

Xxx 0Ova

Sperms

xx xxnormal femalesxxx xoSuper females Turnersx

xy xy

normal malexxy yoKleinefelter non-viabley

chromosomal abrerations

Documents