Chromosomal Disorders Bashdar Mahmud Hussen M.Sc. Biotechnology Hawler Medical University, Iraq bashdar@res.hmu.edu.iq bmhscience@yahoo.com

Genetic diseases traditionally - 3 types of diseases 1. genetically determined 2. environmentally determined 3. 1. + 2. about 50% of spontaneous abortuses have chromosomal aberration hereditary = derived from parents familial = transmitted in the gametes through generations congenital = present at birth (not always genetically determined

Numerical abnormalities euploidy - normal 46 (2n) polyploidy (3n or 4n) - spontaneous abortion Aneuploidy (whole chr. Missing or extra trisomy (2n+1) - 47 - compatible with life monosomy (2n-1) - autosomal - incompatible with life - sex chromosomal - compatible with life

Numerical Abnormalities Trisomy 21 (Down syndrome) Trisomy 18 Trisomy 13 Klinefelter Syndrome Turner Syndrome Triple X Syndrome Most common chromosome abnormalities in aborted fetuses is: Turner syndrome (45,X) triploidy trisomy 16

No. of genes on chromosome 21 Mosaic Down syndrome 3. Causes of trisomy 4. Maternal age Final pair is called the "sex chromosomes." The sex chromosomes an individual has determines that person's gender; females have two X chromosomes (XX), and males have an X and a Y chromosome (XY).

Less frequent disorders Trisomy 18 (Edwards syndrome) 1:6000 95% (extra number), 5% (translocation) 90% of infants die Trisomy 13 (Patau syndrome) 1:10000 They have cleft lip and palates, extra fingers and toes, malformed and rotated internal organs

Klinefelter Syndrome Found only in males (47, XXY most common) I in 500 males Nondisjunction of XX homologues Sterility Testicular atrophy individual is born with three sex chromosome, XXY

Turner Syndrome Found in women with unmistakably female appearance Absence of ovaries (gonadal dysgenesis) Usually (45, X) missing one X chromosome 1. X-Chromosome Monosomy 2. X-Chromosome Mosaicism 3. X-Chromosome Defects ( small or large deletion) individual is born with only one sex chromosome, an X

Triple X syndrome 1 in 1,000 girls are born with Triple X syndrome Menstrual irregularity Delayed speech & language skill A mosaic form also occurs where only a percentage of body cell contain XXX not inherited

Prenatal diagnostics amniocentesis - analysis of amniotic fluid cytogenetic analysis (karyotype) analysis of various specific genes (PCR)

Structural Abnormalities May involve one or more chromosomes Usually result from chromosome breakage The effects of structural changes depend on their size & location loss of chromosomal material is more dangerous than gain abnormalities of sex chromosomes are better tolerated than autosomal, abnormalities of sex chromosomes sometimes symptomatic in adult age (e.g. infertility)

partial monosomy proximal deletion (near to centromer) interstitial deletion subtelomeric deletion

It occurs during meiosis between misaligned homologous chromosomes (unequal crossing-over) Duplications of oncogenes

Non Robertsonian translocation or Robertsonian translocation A chromosome in which the centromere is located quite near one end of the chromosome. Humans normally have five pairs of acrocentric chromosomes

fertility problems.

causes Turner syndrome two identical arms causes Turner syndrome causes Turner syndrome

Chromosome Mutation Animation