Chromosomal Disorders

Hawler Medical University, Iraqbashdar@res.hmu.edu.iqbmhscience@yahoo.com

Bashdar Mahmud HussenBashdar Mahmud Hussen

M.Sc. Biotechnology

Genetic diseasestraditionally - 3 types of diseases1. genetically determined2. environmentally determined3. 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

1. No. of genes on chromosome 21

2. Mosaic Down syndrome

3. Causes of trisomy4. Maternal age

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

Turner Syndrome

• Found in women with unmistakably female appearance– Absence of ovaries (gonadal dysgenesis)– Usually (45, X) missing one X chromosome

1. X-Chromosome Monosomy2. X-Chromosome Mosaicism3. X-Chromosome Defects ( small or large deletion)

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 gainabnormalities of sex chromosomes are better tolerated than autosomal, abnormalities of sex chromosomes sometimes symptomatic in adult age (e.g. infertility)

partial monosomy

1. proximal deletion (near to centromer)2. interstitial deletion3. subtelomeric deletion

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

Robertsonian translocationNon Robertsonian translocation or

fertility problems.

causes Turner syndrome

two identical arms

Chromosome Mutation Animation