Single Gene Disorders Flashcards
Explain dominant and recessive inheritance patterns.
Dominant: Aa x aa
50% not affected; 50% affected
Recessive: Aa x Aa
25% affected; 50% carriers; 25% not affected
Compare and Contract X-linked and autosomal inheritances
auto recessive:
- both sexes affected equally
- parents are carriers
- consanguinitiy present
auto dom:
- both sexes affected equally
- at least 1 parent affected
- homo > hetero
- can be transmitted father to son
x-linked recessive:
- no father/son
- boys > girls
- affected boys usually have unaffected parents
x-dom:
- no father/son
- girls > boys, as males die
- affected girls will have affected fathers
Explain the inheritance of mitochondrial disorders
comes from the mother; cells contain varying fragments of defective mtDNA molecules (heteroplasmy)
Draw and interpret a pedigree
- is disease affecting all children?
no –> father/son transmission?
if not –> more boys than girls –> if yes, auto recessive
if yes –> auto dom/auto recessive –> affected parents? –> auto dom
Explain the impact of consanguinity on the risk for recessive disorders.
Causes the rare allele to stay in the population; associated with coiffienct of inbreeding; there is a 1/4 change that a child will have the condition.. and a 1/64 change it will be passed on to cousins? or something like that lol.
Describe the implications of incomplete penetrance, variable expressivity, new mutations and triplet expansions on the interpretation of autosomal dominant disorders.
incomplete penetrance: the patient has the disease but does not show symptoms
variable expressivity: the patient has the disease and will show symptoms; but the severity of the symptoms displayed is variable (example: neurofibromatosis)
new mutations: are seen in achondroplasia, etc
triplet expansions: Huntingtons Disease has many CAG repeat regions.. if > 40, they will have early onset; if 35-40.. at a high risk
Contrast haploinsufficiency and dominant negative effect in the development of osteogenesis imperfecta subtypes.
haploinsufficiency: mutation in Type 1 collagen; all the collagen made is normal, but a null mutation is causing the amount produced to be reduced in half.
dominant-negative: mutation causing misfolding of collagen results in dominant/negative affect
Explain the dominant inheritance of familial hypercholesterolemia.
1/500 will get it. 2x if hetero; 4x if homo.
Contrast the effects of gain-of-function and loss-of-function mutations in the RET gene.
LOF: Hirschsprung disease; impairs development of neurons that population the colon, giving rise to aganglionic colon
GOF: Multiple Endocrine Neoplasia (MEN); RET is constiutiively active, and causes proliferation of neuroendocrine cells
What 2 disorders are autosomal recessive? what 6 are autosomal dominant?
recessive:
1. PKU (inborn error of metabolism)
2. Cystic Fibrosis
dominant:
1. neurofibromatosis
2. huntingtons
3. Achondroplasia
4. Osteogenesis Imperfecta
5. Familial Hypercholesteremia
6. Li Fraumeni
What diseases are x-linked recessive? X-linked dom?
X-linked recessive:
Duchenne and Becker Muscular Dystrophies; mutation in dystrophin gene
X-linked dom: Incontinentia Pigmenti: results from defect in NEMO
Mitochondrial disease?
LHON: mutation in ND1 gene; inhibits ETC
What is allele heterogeneity?
different mutations in the same gene cause different phenotypes (can be gain-of-function or loss-of-function)
What is locus heterogeneity?
mutations in different genes cause the same phenotype
What are modifiers?
individual genetic background modifies the protein
