mendelian disorders and multifactorial disease Flashcards
PKU and CF
Autosomal recessive
2 X-linked conditions
DMD, Hemoph A
Autosomal dominant condition
Familial hypercholest
Males and females pass on the trait, MALE TO MALE transmission CAN occur
Autosomal dominant
Disease in AD condition is due to
- haploinsufficiency
- Dominant negative effect
- Mutation enhances protein function
- loss of the normal copy can happen
Proportion of individuals with a mutation causing a particular disorder who exhibit clinical symptoms
Penetrance - ALL OR NOTHING
Penetrance may be explained by
Modifier genes
Variable expressivity is
different DEGREES of severity or manifestations of a disease in different individuals who have mutations int he same gene
e.g.
Variable expressivity can be explained by
differences due to genotype/phenotype effects
presence of modifier genes
environmental factors
Example of AD disorder with variable expressivity
Lynch syndrome (with uterine cancer) PCKD Marfan syndrome FAP 100% penetrant Hereditary breast/ov ca
2 yr old recurrent resp infection with Pseudo Aerugonisoa
autosomal recessive CF
CF predominantly
Northern european 1/2500
NOT usually in multiple generations
important AR conditions
- sickle cell anemia
- Most inborne errors of metabolism - PKU etc.
- Thalessmia
6 yr old with progressive weakness, early death due to resp failure in Fam Hx, enlarged calf muscles
DMD
elevated CK levels 50x normal
mutation in dystrophin
one third of DMD cases are thought to be the result of
2/3 of DMD cases
new mutations
have carrier mothers
