Chromosomes

Question 1

Examples of breakage syndromes

Answer 1

Bloom
Fanconi anaemia
Njemegen
Roberts
xeoderma pigmentosa
Ataxia telangiestesia
Cockayne syndrome
Trichothiodystrophyb(TTD)

Question 2

Symptoms of fanconi anaemia

Answer 2

Pre and postnatal growth retardation
Microcephaly
Developmental delay
Skeletal malformations (radial defects and hypoplastic left thumb), pancytopaenia, progressive bone marrow failure
Increased susceptibility to leukaemias and other malignancies

Question 3

Symptoms of Bloom syndrome

Answer 3

Growth deficiency
Characteristic facies - triangular face, long narrow head, cheepine hypoplasia, nasal prominence, sun sensitive skin rash, telangietatic (spider veins on skin), hypo/hyper pigmented skin, immunodeficiency, predisposition to malignancy, butterfly rash, recurrent respiratory tract infections, makes infertile, females difficult, leukaemias around 23, solid cancers e.g. breast and gastro-intestinal by age 35

Question 4

What gene causes bloom disease and what is its function?

Answer 4

BLM

DNA helipads RECq protein at 15q26
Caretaker tumour suppressor gene, essential for genome stability and suppressed inappropriate recombination
Part of complex that dissolves double Holliday junctions at stalled replication forks
Role in telomere maintenance

Question 5

Symptoms of ataxia telangiestsia

Answer 5

Occurs telangiectesia, truncates ataxia, occulomotorr apraxia, wheelchair by 15, brain cells die, susceptible to x-ray

Pulmonary disease leading cause of death

Question 6

Genetics of ataxia telangiectasia

Answer 6

ATM gene at 11q22.3
Carrier frequency 1:300
Most compound get but some mutations have dominant negative effect
Define-threonine kinase involved in signalling DNA breaks
Similar role to BRCA
Delays cells in g phases

Question 7

Breakage syndrome with no predisposition to cancer

Answer 7

Cockayne syndrome