Lecture 16- Chromosomal Disorders

Question 1

human karyotype

Answer 1

23 pairs of chromosomes. 22 pairs of autosomal and 2 sex chromosomes

Question 2

P and Q arms of chromosome

Answer 2

short arm-P

long-Q

Question 3

aneupliody

Answer 3

gain or loss of a whole chromosome. most likely to arise as a result of nondisjunction at meiosis 1 or 2.
loss of one-monosomy
gain of one-trisomy
a numerical abnormality- often result in spontaneous abortion

aneuploidy of the sex chromosomes can occur
kinfelter syndrome-XXY
turner syndrome-X

Question 4

Mosaicism

Answer 4

Somatic mosaicism
–  Structural or numerical
–  Occurs post zygote formation
–  Mitotic non disjunction
–  3% Downs cases

during mitotic division there is non disjunction of the chromosomes 21, causing one cell to have 45 and one 47. the 45 is unviable.

Question 5

structural chromosomal abnormalities

Answer 5

a break can occurr in one or more chromosomes. some breaks may result in overall loss or gain of genetic material, others in rearrangement of genetic material but with no overall gain or loss. can be constitutional or acquire (cancer).

• reciprocal translocation
• robertsonian translocation
• inversion
• deletion

Question 6

Reciprocal translocation

Answer 6

two way exchange of material between two non homologous chromosomes. if balanced then phenotype normal as no material was gained or lost.

carriers of balanced translocations can present with recurrent miscarriages, birth of a dysmorphic baby with an unbalanced translocation and oligospermia in male carriers

Question 7

Robertsonian translocation

Answer 7

quite common with carrier frequency 1:1000.
individual will have 45 chromosomes but will be phenotypically normal.
occur between two homologous or non homologous afrocentric chromosomes only (13,14,15,21 and 22)

Question 8

inversion

Answer 8

intra-chromosomal structural rearrangement, which involves two breaks on the same chromosome-the resulting chromosome segment rotates by 180 and reinserts itself.
can involve both chromosome arms and the centromere (pericentric) or only one arm (paracentric).

carriers are usually phenotypically normal, with a very low risk of having abnormal offspring and are often ascertained fortuitously. some inversions eg. pericentric inversion are common polymorphic variants and are not clinical significant

Question 9

Chromosome deletion

Answer 9

A terminal deletion is caused by a single break at the terminal region of a chromosome and loss of that fragment.

An interstitial deletion is caused by two breaks in the same chromosome and loss of the intervening fragment

clinical examples of congenital disorder due to constitutional deletions include
-Cri-du-chat syndrome
•  cat-likecryat birth
•  verypoorspeech
•  inabilitytowalk
•  prematureageing
-Prader-Willi/Angelman syndrome

Question 10

FISH-fluorescant In situ Hybridisation

Answer 10

by co-denaturing and then annealing the target and probe DNA, specific nucleic acid sequences present on the cytological material can be visualised under UV fluoresence

Question 11

specimens suitable for FISH

Answer 11

any type of tissue with a viable nucleus
Blood, Skin, Bone marrow, tumours,
amniocytes, paraffin embedded tissues Dividing and non-dividing cells

Question 12

Applications for G banding, karyotype analysis

Answer 12

Suspected congenital disorders • eg Down syndrome, dysmorphic baby • Products of conception
• Recurrent miscarriages
• Cancer / Leukaemia
• Diagnostic and prognostic marker

Question 13

Comparitve Genomic hybridisation

Answer 13

compares normal and target DNA by scanning entire genome for overall gain or loss of DNA