Chromosomal aberrations

In this presentation i have discussed some abnormalities due to chromosomal aberration due to change in number or change in structure of chromosome.

1. Chromosomal Aberrations
Mohsin Raza & Farrukh Ahmad

2. Types
Numerical -change in no.
Structural –change in structure

4. Monosomy
loss of single chromosome
Monosomy of autosomes is lethal
Turner syndrome XO i.e. loss of sex chr.
Cause : 1. non disjunction –one gamete receives 2 copies of
homologous chr.& other will have no copy
2. loss of chr.As it move towards pole of cell during anaphase .

5. Trisomy
Gain of homologous chr.
Trisomy 21 (down’s ) , trisomy 18 , klinefelter’ssyndrome
(47 XXY)

6. Nondisjunction
Failure of bivalents to separate during meiosis 1 , the gametes get both
homologues of one chrpair
Sometimes in meiosis 2 when sister chromatids fail to separate -gets 2
copies of one of the homologues
It can also occur during early mitotic div. of zygote -there will be
presence of 2 or more cell lines

7. Nondisjunction

8. Causes
Aging effect on primary oocyte
Radiation
Delayed fertilization after ovulation
Effects –monosomy or trisomy

9. Polyploidy
Multiples of haploid no.
Triploidyor tetraploidy
Foetusdoes not survive
Cause -1. retention of polar body
2. Formation of diploid sperm
3. Dispermy–fertilization by 2 sperms

10. Triploidy

11. Structural Abnormalities
Rearrangement because of chr.Breakage & subsequent reunion in
a different configuration
Balanced –chr.Complement is complete
Unbalanced –when there is incorrect amount of genetic material

12. Structural Abnormalities
1. Translocations –reciprocal or robertsonian
2. Deletions
3. Insertions
4. Inversions –paracentric or pericentric
5. Ring chr.
6. Isochromosomes

13. Translocation
Transfer of genetic material from one chrto
another
Reciprocal –2 chrbreak & exchange fragments
no. remains 46 unique to a particular family chr
imbalance during gamete formation

14. Robertsonian Translocation
Breakage of 2 acrocentric chrnear centromeres
& fusion of long arms
Short arms lost –no importance they contain
genes for rRNA
Chrno. 45 , but no loss of genetic material
hence balanced

15. Robertsonian Translocation

16. Deletions
❑Loss of part of chr.
• Deletions of larger portions are usually incompatible with life
• 10-15% are due to balanced translocations in one parent 85-90%
are true deletions

17. Deletions
Terminal –Cri –du chat syndrome ( 5p-)
Interstitial –2 breaks & middle part is lost eg.pradervilli syndrome
Microdeletions

18. Insertions
Rare nonreciprocal type of translocation
A segment of chrgets inserted into another chr

19. Inversion
2 break rearrangement
Segment is reversed
3. Pericentric –when centromere is involved
4. Paracentric –only one arm is involved

20. Ring Chromosomes
•Break occurs in each arm & the 2 sticky ends join
Distal fragments are lost
1/5 cases of turner’s syndrome

21. Philadelphia Chromosome
Involves translocation between long arm of
chr22 & 9
There is shorter arm of chr22 called
philadelphiachr
Found in chronic myelogenous leukemia
Indicates better out come

22. Philadelphia Chromosome

23. Down’s Syndrome
First identified by Dr Langdon Down in 1866
Trisomy 21
1in 700 live births
Associated with increased maternal age

24. Clinical Findings
Newborn –hypotonia , increased sleepiness ,excess nuchal skin
Mental retardation
Small stature
Craniofacial findings –brachycephaly ( flat occiput ) , epicanthic
folds , upward slanting eyes , protruding tongue, low set ears , flat
nose , low nasal bridge , high arched palate

25. Cont…..
❑Short broad hands
❑Clinodactyly ( incurving ) little finger
❑ASD,VSD , PDA
❑Anal duodenal atresia
❑Happy & affectionate

26. Down’s Syndrome

27. Edward’s Syndrome
Trisomy 18
Described by Edward in 1960
Rare to find live born
Do not live beyond few months
Features –mental retardation , failure to thrive , hypotonia ,
prominent occiput , low set ears , receding jaw , short sternum ,
clenched fists, rocker bottom feet.

28. Patau’s Syndrome
Trisomy 13
Die in a month
Growth & mental retardation
Sloping forehead , hypertelorism , microphthalmia , cleft lip ,
cleft palate , polydactyly , polycystic kidneys , bicornuate uterus

30. Turner’s Syndrome
X monosomy , 45 X
described by Turner in 1938
Phenotype is female
Short stature
Webbing of neck
Cubitus valgus
Low posterior hair line
Broad chest with widely spaced nipples
High arched palate

31. Coarctation of aorta
VSD
Horseshoe kidney
Renal hypoplasia
Streak gonads
Secondary sexual characters do not develop
Turner’s Syndrome

32. Klinefelter’s Syndrome
Harry klinefelterin 1942
47XXY
Male phenotype with sex chromatin positive
Patients are tall thin , eunuchoid
Poorly developed secondary sexual characters
Testis are small , scrotum & penis show hypoplasia
Pubic ,chin & axillary hair absent

33. Klinefelter’s Syndrome
❑Normal intelligence
❑Testicular biopsy shows hyalinisationof seminiferous tubules
❑Absent spermatogenesis
❑Low serum testosterone , high FSH & LH

34. 5p
-
(cri-du-chat) Syndrome
❑deletion (the length of which may vary) on the
short arm of chromosome 5
❑small at birth, may have respiratory problems ,
the larynx doesn't develop correctly, which
causes the signature catlike cry.
❑microcephaly), an unusually round face, a small
chin, widely set eyes, folds of skin over their
eyes, and a small bridge of the
nose.

35. 5p
-
(cri-du-chat) Syndrome