Chromosomal Abnormalities PDF

Chromosomal abnormalities Dr.seham ahmed Abdel Aziz Lecturer of histology and cell biology  ❖ What is genetics? It is the study of hereditary and its variation ❖ Gene -Is the basic unit of inheritance Formed of DNA -Organize formation of proteins  ❖ W...

Chromosomal abnormalities Dr.seham ahmed Abdel Aziz Lecturer of histology and cell biology  ❖ What is genetics? It is the study of hereditary and its variation ❖ Gene -Is the basic unit of inheritance Formed of DNA -Organize formation of proteins  ❖ What is the chromosome? Thread like structure of DNA carries the genes for transmission of hereditary information  ❖ HUMAN CHROMOSOMES - Each chromosome formed of two chromatids - Each chromatid has short arm called ….P arm - Long arm called….Q arm - The two chromatids are attached at appoint called centromere - On the side of centromere there are points - called kinetochore the site of attachment of spindle fibers  ❖ Diploid and haploid The state in which there are two copies of each chromosome called diploid Only on copy called haploid All somatic cells have diploid number of chromosomes Gametes (ova testes)have haploid number of chromosomes  ❖ Telomers ❖ A telomere is a region of repetitive sequences of DNA at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes as TTAGGG Chromosomal Abnormalities Structural Abnormalities Numerical Abnormalities  Causes of Chromosomal abnormalities: ❑ Hereditary in the family. ❑ Old age pregnant women. ❑ Infection with German measles during pregnancy. ❑ Exposure of pregnant women to radiation or autoimmune disease. ❖ Structural Abnormalities 1. Deletions (del) 2. Ring Chromosomes (r) 3. Inversions (inv) 4. Translocation 5. Isochromosomes Deletions (del) Deletions result in loss of a chromosomal part, loss of a segment, and reunion of the breakpoints.  Ring Chromosomes (r) ring chromosome A structurally abnormal chromosome in which the end of each chromosome arm has been lost and the broken arms have been reunited in ring formation  Inversions (inv) a chromosomal segment breaks, reorients 180°, and reinserts itself.  Translocation is the transfer of segments between chromosomes Isochromosomes is abnormal transverse division of the centromere separating the two arms instead of longitudinal division separating individual chromatids.  ❖ Numerical Chromosomal Abnormalities Changes in the number of chromosomes: Polyploidy Aneuploidy  Polyploidy: is abnormal duplication of haploid number of chromosomes. Somatic cells contain multiples of haploid number of chromosomes 3n, 4n, 5n etc. These numerical aberrations are incompatible (impossible to continue) with life & cause miscarriage (loss of pregnancy). Mechanism of Polyploidy (a) Failure of pulling apart of 2 chromatids to opposite ends after metaphase stage of mitosis. (b) Reduplication of chromosomes without dissolving of nuclear membrane. (c) Failure of cytoplasmic division.  Aneuploidy is the addition (Trisomy) or loss (Monosomy) of a chromosome and may affect autosomes or sex chromosomes. Aneuploidy of Autosomes: Trisomy (Trisomy of Autosomes (13,18,21)) is the presence of an additional chromosome to the usual pairs. It has been reported in all autosomes except chromosome number 1. The commonest is trisomy 21, which means the presence of 3 of chromosome (21) in Down’s syndrome or Mongolism. Trisomy 13 or D-trisomy (Patau syndrome) Trisomy 18 or E-trisomy (Edward syndrome) Trisomy 21 or G-trisomy (Down syndrome) Patau syndrome Edward syndrome Down syndrome Down syndrome  Monosomy is the missing of one chromosome from the usual pairs and monosomy of autosomes is lethal.  Aneuploidy of Sex chromosomes Trisomy is presence of an additional sex chromosome (usually X). Normally, males have X & Y sex chromosomes and need both for sex differentiation, while female cells possess double X chromosomes. Klinefelter syndrome: In this disease males have positive sex chromatin (47, XXY) presenting with poor musculature, underdeveloped genitalia, infertility and gynecomastia. They have higher risk for breast cancer. Monosomy of X chromosome is detected in females (45, X) in Turner syndrome. Turner syndrome or gonadal dysgenesis is a common abnormality, where one X chromosome is missing. Barr body is absent. In this disease females have primary amenorrhea, underdeveloped genitalia and secondary sex characters, infertility, together with renal and cardiac anomalies.  SEX CHROMATIN (BARR BODY) General Characteristics:  The sex chromatin represents an X chromosome, which remains inactive (coiled), during the interphase, stained with basic dyes (Hx) and is Feulogon +ve.  It occurs in females as their cells posses double X chromosomes, while males have Y & X sex chromosomes and need both for sex differentiation as sperms contain either Y or X sex chromosome, while ova contain X sex chromosome.