B2.026 Disorders with Complex Inheritance Flashcards
(35 cards)
what is the definition of complex/multifactorial inheritance?
type of non-Mendelian inheritance shown by traits that are determined by a combination of multiple factors (genetic and environmental)
what kinds of genetic variants cause complex diseases?
common variants
there are usually variants in multiple genes; no one of which could cause a disease alone but the combination of multiple mutations and environmental factors = complex disorder
can a single gene disorder produce a phenotype that is completely independent of other genetic, environmental, or developmental factors?
no
what kinds of diseases are minimally affected by other genes or the environment?
Mendelian
autosomal dominant, autosomal recessive, X-linked
clear inheritance pattern
how are diseases classified when they show loss of a clear inheritance pattern, but are still familial?
complex
how are diseases classified when they begin to show a loss of familial clustering?
sporadic
what type of inheritance is associated with cystic fibrosis?
autosomal recessive
how frequent are cystic fibrosis carriers in the population?
1/20
what is common amongst all forms of CF?
mutations in the CFTR gene
what is unique about CF?
displays a lot of clinical heterogeneity
what are possible explanations for clinical heterogeneity in CF?
allelic heterogeneity
effects of other modifying loci
nongenetic factors
what is the type of inheritance is associated with Huntington’s disease?
autosomal dominant
describe incomplete penetrance in the context of huntington’s disease
individuals with 36-41 CAG repeats may or may not express the disease clinically due to presence of different modifier genes/chaperone levels
describe the inheritance pattern of myotonic dystrophy
autosomal dominant inheritance with variable expressivity due to anticipation pleiotrophy and incomplete penetrance
what is pleiotrophy?
one gene affecting multiple phenotypes
what is anticipation?
slippage in transcription that increases # of repeats in a sequence
what is reverse anticipation?
slippage in transcription that shorted the repeat sections
where does cancer fall on the continuum of inherited diseases?
can be any type
mostly sporadic, followed by familial, with a few genetic
what is one big difference between disorders w complex inheritance vs mendelian disorders?
complex much more common in population
what are 3 things that complex diseases can exhibit?
familial clustering (inherit blocks of genes, more variants can be present within a fam)
higher recurrence risk among relatives
genetic concordance between monozygotic twins
what is the threshold model?
concept that individuals are more or less susceptible to disorders requiring a threshold for the expression of that trait
how does increased incidence of a complex disease in a family affect recurrence risk?
increases
what causes diseases with 100% concordance in monozygotic twins?
genetic factors
what can be said about diseases that are more concordant in MZ than DZ twins?
stronger genetic bs environmental component
