genetics

Question 1

autosomal dominant mutations

Answer 1

achondroplasia

marfan syndrome

neurofibromatosis

Question 2

achondroplasia

Answer 2

autosomal dominant (may be de novo)

FGFR3 gene mutation

short limbed dwarfism

related to PATERNAL age

Question 3

Marfan syndrome

Answer 3

autosomal dominant (may be de novo)

connective tissue disorder, unusually tall

Question 4

neurofibromatosis

Answer 4

autosomal dominant (may be de novo)

less than 100% penetrance

Question 5

germline mosaicism

Answer 5

seen in osteogenesis imperfecta

duchenne muscular dystrophy

Question 6

compound heterozigosity

Answer 6

different allelic mutations at the same locus

eg

cystic fibrosis pGLy542x/p/Phe508del

haemoglobinopathies

Question 7

X-linked recessive

Answer 7

females can be affected due to non-random X-inactivation (less severe) >> chance expression in certain tissues
:

heart in Duchenne Muscular dystrophy carriers (death before 25yrs)

kidney in x-linked Alprot’s disease >> chronic renal failure

brain in Fragile X syndrome (learning difficulties)

Turner syndrome 45,X

Question 8

X inactivation

Answer 8

rnadom, inactivated by METHYLATION

Question 9

X-linked dominant

Answer 9

males affected more than females

females express mosaic patterns

disease may be lethal for males

Question 10

genetic heterogeneity

Answer 10

phenotype can be caused by a mutation in more than one gene, autosomal or sex-linked

conditions that do this show locus heterogeneity, eg:

Non-syndromic sensorineural hearing loss

Retinitis pigmentosa (eye defects>> blindness)

CHarcot-Marie-Tooth disease (motor and sensory neuropathy)

Allelic heterogeneity means that different mutations within a single gene locus (forming multiple alleles of that gene) cause the same phenotypic expression. For example, there are over 1000 known mutant alleles of the CFTR gene that cause cystic fibrosis.

Locus heterogeneity means that variations in completely unrelated gene loci cause a single disorder. For example, retinitis pigmentosa has autosomal dominant, autosomal recessive, and X-linked origins.