Inheritance patterns Flashcards
Familial hypercholesterolaemia Marfans syndrome Adult polycystic kidneys Huntington disease Neurofibromatosis Tuberous sclerosis Myotonic dystrophy Von WIllebrand disease Osteogenesis imperfecta Acute intermittent porphyria Hereditary haemorrhagic telangiectasia Noonan syndrome Hereditary speherocytosis
Autosomal dominant
Penetrance
"Black or white" AD Genotype without any phenotype "skipped generation" Incomplete penetrance = some with mutation have disease, some don't Eg. polydactyly
Expression
“Shades of grey”
AD
Same genotype, variable but always present phenotype
Variable expression = different manifestations
Eg. NF1
Mosaicism
More than one genotype in different cells
- point mutation or chromosomal abnormality
- germline vs somatic
De novo mutations
Common in AD and X-linked disorders
Rare in AR
More severe disorder = more common de novo mutations
Deafness (some) Albinism Wilson disease Sickle cell disease Thalassaemia CF Friedrich ataxia Haemochromatosis Phenylketonuria (PKU) Alpha 1 anti-trypson deficiency Homocystinuria
Autosomal recessive
2 in 3 rule
If a sibling of a person AFFECTED with a recessive syndrome is unaffected by the recessive condition, then they are either:
- heterozygote (carrier) 2/3
- wildtype homozygous 1/3
Incidence
1 / [ (Carrier frequency)2 x 4 ]
Carrier frequency
Square root of (Incidence / 4 )
Hardy Weinberg principle
Allele and genotype frequencies in the population will remain constant in the absence of other evolutionary influences
Haemophilia A G6pd deficiency Fairy disease Ocular albinism Testicular feminisation Chronic granulomatous disease Fragile X syndrome Rett syndrome Colour blindness Duchenne muscular dystrophy Hypophosphataemic rickets
X-linked
Angelman vs Prader Willi
Prader WIlli: absent Paternal allele expression
AngelMAN: absent MAternal allele expression
Loss of 15q12
Beck with Wideman vs Russel Silver
BW: loss of maternal 11p15 expression
BIG
RS: loss of paternal 11p15 expression
SMALL
Loss of 11p15
Mytonic dystrophy
Fragile X
Huntington disease
Some spinocerebellar ataxias
Triplet repeat disorder
Mitochondrial vs X-linked
No male-male
X-linked: males affected exclusively (or more severe than females)
Mitochondrial
- males and females affected to same extent
- no descendants of an affected male can have the disease (this CAN happen in X-linked)
