Chromosomal aberrationsChromosomal aberrations

Types Types

Numerical - change in no.Numerical - change in no. Structural – change in structureStructural – change in structure

MonosomyMonosomy

loss of single chromosome loss of single chromosome Monosomy of autosomes is lethalMonosomy of autosomes is lethal Turner syndrome XO i.e. loss of sex chr.Turner syndrome XO i.e. loss of sex chr. Cause : 1. non disjunction – one gamete Cause : 1. non disjunction – one gamete

receives 2 copies of homologous chr. & receives 2 copies of homologous chr. & other will have no copyother will have no copy

2. loss of chr. As it move towards pole 2. loss of chr. As it move towards pole of cell during anaphase . of cell during anaphase .

Trisomy Trisomy

Gain of homologous chr.Gain of homologous chr. Trisomy 21 (down’s ) , trisomy 18 , Trisomy 21 (down’s ) , trisomy 18 ,

klinefelter’s syndrome (47 XXY)klinefelter’s syndrome (47 XXY)

Nondisjunction Nondisjunction

Failure of bivalents to separate during Failure of bivalents to separate during meiosis 1 , the gametes get both meiosis 1 , the gametes get both homologues of one chr pairhomologues of one chr pair

Sometimes in meiosis 2 when sister Sometimes in meiosis 2 when sister chromatids fail to separate - gets 2 copies chromatids fail to separate - gets 2 copies of one of the homologuesof one of the homologues

It can also occur during early mitotic div. It can also occur during early mitotic div. of zygote - there will be presence of 2 or of zygote - there will be presence of 2 or more cell lines more cell lines

Nondisjunction Nondisjunction

Cause Cause

Aging effect on primary oocyteAging effect on primary oocyte RadiationRadiation Delayed fertilization after ovulationDelayed fertilization after ovulation Effects – monosomy or trisomyEffects – monosomy or trisomy

Polyploidy Polyploidy

Multiples of haploid no.Multiples of haploid no. Triploidy or tetraploidy Triploidy or tetraploidy Foetus does not surviveFoetus does not survive Cause -1. retention of polar bodyCause -1. retention of polar body

2. Formation of diploid sperm2. Formation of diploid sperm

3. Dispermy – fertilization by 2 sperms 3. Dispermy – fertilization by 2 sperms

Triploidy Triploidy

Structural abnormalitiesStructural abnormalities

Rearrangement because of chr. Rearrangement because of chr. Breakage & subsequent reunion in a Breakage & subsequent reunion in a different configurationdifferent configuration

Balanced – chr. Complement is Balanced – chr. Complement is completecomplete

Unbalanced – when there is incorrect Unbalanced – when there is incorrect amount of genetic materialamount of genetic material

Structural abnormalitiesStructural abnormalities

1.1. Translocations – reciprocal or Translocations – reciprocal or robertsonianrobertsonian

2.2. DeletionsDeletions

3.3. Insertions Insertions

4.4. Inversions – paracentric or pericentricInversions – paracentric or pericentric

5.5. Ring chr. Ring chr.

6.6. Isochromosomes Isochromosomes

Translocation Translocation

Transfer of genetic Transfer of genetic material from one chr material from one chr to anotherto another

Reciprocal – 2 chr Reciprocal – 2 chr break & exchange break & exchange fragments fragments

no. remains 46no. remains 46

unique to a particular unique to a particular familyfamily

chr imbalance during chr imbalance during gamete formation gamete formation

Robertsonian translocationRobertsonian translocation

Breakage of 2 Breakage of 2 acrocentric chr near acrocentric chr near centromeres & fusion centromeres & fusion of long armsof long arms

Short arms lost – no Short arms lost – no importance they importance they contain genes for rRNAcontain genes for rRNA

Chr no. 45 , but no Chr no. 45 , but no loss of genetic loss of genetic material hence material hence balancedbalanced

Deletions Deletions

Loss of part of chr.Loss of part of chr.• Deletions of larger portions are usuallyincompatible with life• 10-15% are due to balanced translocationsin one parent85-90% are true deletions

Deletions Deletions

Terminal – Cri – du chat syndrome Terminal – Cri – du chat syndrome ( 5p-)( 5p-)

Interstitial – 2 breaks & middle part is Interstitial – 2 breaks & middle part is lost eg. prader villi syndrome lost eg. prader villi syndrome

Microdeletions Microdeletions

Insertions Insertions

Rare nonreciprocal type of Rare nonreciprocal type of translocation translocation

A segment of chr gets inserted into A segment of chr gets inserted into another chranother chr

Inversion Inversion

2 break 2 break rearrangement rearrangement

Segment is Segment is reversedreversed

1.1. Pericentric – when Pericentric – when centromere is centromere is involvedinvolved

2.2. Paracentric – only Paracentric – only one arm is involvedone arm is involved

Ring chromosomesRing chromosomes

Break occurs in Break occurs in each arm & the 2 each arm & the 2 sticky ends joinsticky ends join

Distal fragments Distal fragments are lostare lost

1/5 cases of 1/5 cases of turner’s syndrometurner’s syndrome

Philadelphia chromosome Philadelphia chromosome

Involves translocation between long Involves translocation between long arm of chr 22 & 9 arm of chr 22 & 9

There is shorter arm of chr 22 called There is shorter arm of chr 22 called philadelphia chrphiladelphia chr

Found in chronic myelogenous Found in chronic myelogenous leukemialeukemia

Indicates better out comeIndicates better out come

Down’s syndromeDown’s syndrome

First identified by Dr Langdon Down First identified by Dr Langdon Down in 1866in 1866

Trisomy 21Trisomy 21 1in 700 live births1in 700 live births Associated with increased maternal Associated with increased maternal

ageage

Clinical findingsClinical findings

Newborn – hypotonia , increased Newborn – hypotonia , increased sleepiness , excess nuchal skinsleepiness , excess nuchal skin

Mental retardationMental retardation Small statureSmall stature Craniofacial findings – brachycephaly ( flat Craniofacial findings – brachycephaly ( flat

occiput ) , epicanthic folds , upward occiput ) , epicanthic folds , upward slanting eyes , protruding tongue, low set slanting eyes , protruding tongue, low set ears , flat nose , low nasal bridge , high ears , flat nose , low nasal bridge , high arched palate arched palate

Short broad handsShort broad hands Clinodactyly ( incurving ) little fingerClinodactyly ( incurving ) little finger ASD,VSD , PDAASD,VSD , PDA Anal duodenal atresiaAnal duodenal atresia Happy & affectionateHappy & affectionate

Edward’s syndromeEdward’s syndrome

Trisomy 18Trisomy 18 Described by Edward in 1960Described by Edward in 1960 Rare to find live bornRare to find live born Do not live beyond few monthsDo not live beyond few months Features – mental retardation , failure to Features – mental retardation , failure to

thrive , hypotonia , prominent occiput , low thrive , hypotonia , prominent occiput , low set ears , receding jaw , short sternum , set ears , receding jaw , short sternum , clenched fists, rocker bottom feet.clenched fists, rocker bottom feet.

Patau’s syndromePatau’s syndrome

Trisomy 13Trisomy 13 Die in a monthDie in a month Growth & mental retardationGrowth & mental retardation Sloping forehead , hypertelorism , Sloping forehead , hypertelorism ,

microphthalmia , cleft lip , cleft microphthalmia , cleft lip , cleft palate , polydactyly , polycystic palate , polydactyly , polycystic kidneys , bicornuate uteruskidneys , bicornuate uterus

Turner’s syndromeTurner’s syndrome

X monosomy , 45 XX monosomy , 45 X described by Turner in 1938described by Turner in 1938 Phenotype is femalePhenotype is female Short stature Short stature Webbing of neckWebbing of neck Cubitus valgusCubitus valgus Low posterior hair lineLow posterior hair line Broad chest with widely spaced nipplesBroad chest with widely spaced nipples High arched palateHigh arched palate

Congenital malformations Congenital malformations

Coarctation of aortaCoarctation of aorta VSDVSD Horseshoe kidneyHorseshoe kidney Renal hypoplasiaRenal hypoplasia Streak gonadsStreak gonads Secondary sexual characters do not Secondary sexual characters do not

developdevelop

Klinefelter’s syndromeKlinefelter’s syndrome

Harry klinefelter in 1942Harry klinefelter in 1942 47XXY47XXY Male phenotype with sex chromatin positiveMale phenotype with sex chromatin positive Patients are tall thin , eunuchoid Patients are tall thin , eunuchoid Poorly developed secondary sexual Poorly developed secondary sexual

characters characters Testis are small , scrotum & penis show Testis are small , scrotum & penis show

hypoplasiahypoplasia Pubic ,chin & axillary hair absentPubic ,chin & axillary hair absent

Normal intelligenceNormal intelligence Testicular biopsy shows hyalinisation Testicular biopsy shows hyalinisation

of seminiferous tubulesof seminiferous tubules Absent spermatogenesisAbsent spermatogenesis Low serum testosterone , high FSH & Low serum testosterone , high FSH &

LHLH

deletion (the length of which may vary) on deletion (the length of which may vary) on the short arm of chromosome 5 the short arm of chromosome 5

small at birth, may have respiratory problems small at birth, may have respiratory problems , the larynx doesn't develop correctly, which , the larynx doesn't develop correctly, which causes the signature cat-like cry. causes the signature cat-like cry.

microcephaly), an unusually round face, a microcephaly), an unusually round face, a small chin, widely set eyes, folds of skin over small chin, widely set eyes, folds of skin over their eyes, and a small bridge of the nose. their eyes, and a small bridge of the nose.

small at birth,