Please enable JavaScript.
Coggle requires JavaScript to display documents.
MM16: Mendelian Genetics 2 (ii) (Triplet repeat disorders (Fragile X…
MM16: Mendelian Genetics 2 (ii)
Extra-Nuclear Inheritance
mtDNA
mitochondrial
small (16000 bps) loop
maternally transmitted
mitochondria are in tail of sperm + don't get delivered to ovum in fertilisation
homoplasmy: cell has uniform collection of mtDNA (completely normal or completely mutant, with severe early onset)
heteroplasmy: cell has mixed collection of mtDNA (normal + mutant)
abnormal mitochondria
skeletal/cardiac muscle problems, neurological problems
e.g. Leber's hereditary optic atrophy
loss of central vision in late 20s
less energy available to optic N + retina
transmission from mother equally to sons + daughters
Triplet repeat disorders
monogenic (single gene defects)
allelic heterogeneity: different mutations, same gene, different phenotypes/severities
general pop has sequences of 3bp repeats in their genome
normal, not disease-causing up to a specific no.
exceeds normal limit = mutation
polymorphic: no. of repeats differs from person to person
@ upper limit of normal repeats= premutation
more susceptible to expand + cause disease through DNAP slipping (DNAP more likely o make mistakes when reading lots of repeats)
can be dom, rec or x-linked
unstable expansion, can be...
subtle: 1/2 repeats expanded per replication
explosive: rapid expansion
anticipation (the Sherman Paradox)
expansion from 1 generation to the next causes younger onset age + increased severity
Fragile X Syndrome
MODIFIED X-linked dom
most common inherited mental retardation (accounts for 4-8% male cases)
incidence: 1 in 2000-4000 in males, 1 in 8000 in females
characteristic facial appearance: strong jaw + large ears
breakage on x chromo, in FMR1 gene - CGG repeat in 5' UTR
10-50: normal
50-200: permutation
200+: mutation
explosive expansion
maternal parent of origin
Huntington's
GAG repeat in Huntingtin gene on chromo 4
9-28: normal
29-35: premutation
36+: mutation
autosomal dominant
subtle expansion
anticipation
paternal parent of origin
parent of origin effects
phenotype depends on whether mutation is inherited from mother or father
Myotonic dystrophy
Autosomal dom
CTG repeat in DMPK gene
Friedrick's ataxia
Autosomal rec
GAA triplet in Frataxin gene
spinocerebellar ataxia
autosomal dom
GAG repeat in ataxin 7 gene