CHROMOSOMAL ABNORMALITIES Chromosomal Abnormalities

The defects are classified as abnormalities of number or structure of chromosomes (autosomes and sex chromosomes)

Numerical defects - are abnormalities of the number of chromosomes (46), Examples: trisomy 21 (Down syndrome), trisomy 18, trisomy 13, Klinefelter syndrome (47,XXY) Turner syndrome (45, X) Structural defects - result from chromosome breakage and rearrangement.

Possibilities include unbalanced translocation, deletion, duplication, inversion, isochromosome and centric fragment. Examples: cri du chat syndrome (5q deletion), Wilms tumor with aniridia (11 q deletion), Prader-Willi syndrome MOSAICISM

Presence of 2 or more populations of cells with different genotype in one individual, who has developed from a single fertilized egg. Phenomenon was developed by Curt Stern. Can result from Chromosomal non-disjunction Anaphase-lag Endoreplication Mutation in one cell during development Variations in Chromosomal Number • Euploidy – the usual number and sets of chromosomes

• Polyploidy – the presence of three or more complete sets of chromosomes

• Aneuploidy – the presence of additional chromosomes or missing individual chromosomes ISCN NOMENCLATURE International system for human cytogenetic Nomenclature p(petite) - short arm q (queue) - long arm pter - end of the short arm qter - end of the long arm cen - Centromere Single Chromosome Disorders

1.Deletion - portions of the chromosome are lost (genetic material is missing); 2. Duplication - genetic material is present twice; 3. Inversion - parts of the chromos”) ome are flipped (genetic material is “flipped Two Chromosome Disorders Both types are calle“translocation”

Insertion • Genetic material is added from another chromosome when cells go through meiosis, parts of the chromosomes stick together and switch Translocation • Material is swapped with another chromosome

Chromosomal non-disjunction: when cells go through meiosis the chromosomes don’t separate correctly and either too many or not enough are passed on. NUMERICAL ABBERATION Klinefelter Syndrome

• Chromosome complement: 47,XXY

• Phenotype: Male

• Incidence: 1:1000 Klinefelter syndrome: Karyotype Features of Klinefelter Syndrome

• Tall stature; thin build; • Gynaecomastia long lower limbs • Low level of intelligence • Testicular atrophy • Serum testosterone levels • Female pattern of pubic low to normal hair • FSH and LH levels very high • High pitched voice • Sex chromatin positive • Infertility (aspermatogenesis) Triple X Syndrome (Superfemale)

• Chromosome complement: 47,XXX

• Phenotype: Female

• Incidence: 1:1000 Features of Triple X Syndrome

• Normal in appearance • Wide-set eyes • Difficulty in speech, • Amenorrhoea learning and emotional • Expressionless face responses • Enamel hypoplasia • Mild mental • Deficient language retardation in 15-25% skills cases • Delayed development • Two sex chromatin Barr of motor skills bodies • Infertility Superfemale: Karyotype Double Y Syndrome

• Chromosome complement: 47,XYY

• Phenotype: Male

• Incidence: 1:1000 Features of Double Y Syndrome

• Normal in appearance

• Tall stature

• Aggressive behaviour

• Problems in motor and language development MONOSOMY (2n-1) Lack of one chromosome of the normal complement. eg. monosomy of the sex chromosome 45 , X causes Turner’s Syndrome Turner’s Syndrome Background: Described in 1938 by Henry Turner Cause isolated in 1960 (loss of one/part of one sex chromosome)

Physical Symptoms: •Short Stature (mean height < 5 feet) •Failure to develop secondary sex characteristics •Maldeveloped Ovaries (infertility; high risk of ovarian cancer) •Variety of medical problems: cardiovascular, kidney, pancreas, skeletal, thyroid: MARKED VARIABLE EXPRESSIVITY •Minor physical anomalies: webbed neck, low set ears, puffy hands and feet: MARKED VARIABLE EXPRESSIVITY

Behavioral Symptoms: •Normal intelligence •Normal personality (problems of self-esteem and body image that may be associated with physical anomalies) •Lowered spatial-visualization and quantitative reasoning •? Higher stereotypical feminine interests Turner’s Syndrome Karyotype TRISOMY( 3n ) Presence of three copies instead of normal two of a particular chromosome. Eg.- Trisomy of chromosome 21 is Down Syndrome Trisomy of chromosome 18 is Edward Syndrome Trisomy 13 is Patau Syndrome Down Syndrome DOWN SYNDROME DOWN SYNDROME( Trisomy of 21 ) TURNER’S SYNDROME (Monosomy of X) Prader-Willi Syndrome

Angelman Syndrome

Normal Deleted Chr 15 Chr 15

Prader Willi Probe with control chromosome 15 probe

From Medical Genetics (Jorde, Carey, Bamshad, White; 2nd Ed.)

Disclaimer

Disclaimer

This study material has been prepared during COVID 19 pandemic for convenience of the students. This material has been prepared from Ref. Books, Online Books and Materials etc. It will be used only for non commercial purposes. THANK YOU