multifactorial inheritance/common diseases Flashcards
what is the multifactorial mechanism of disease?
combo of genetics and environment
why do some traits “run in the family” but exhibit no defined inheritance pattern?
could be autosomal dominant with variable expression/reduced penetrance or the influences of multiple genes and their environment
what are “polygenic” traits?
combo of multiple genes
what are the characteristics of “continuous” traits?
distributed in a bell-curve
caused by the combined action of many genes
do not follow mendelian patterns
what is the additive model?
states that each gene adds an incremental amount to the phenotype
(more genes involved = increased # phenotypes observed)
what is the threshold model typically applied to?
birth defects
what does the threshold model follow?
the threshold of liability: for multifactorial dz, there is a threshold of liability that must be crossed before the dz is expressed
what increases the recurrence risk in multifactorial traits? (4)
- increasing severity
- increased # of affected family members
- at risk child is member of the more frequently affected sex
- proband is a member of the less frequently affected sex
what decreases the recurrence risk in multifactorial traits? (1)
decreasing degree of relatedness
what are 2 conditions that follow the threshold model?
pyloric stenosis and neural tube defects
in pyloric stenosis, which affected sex is more likely to have affected offspring? which offspring are more likely to be affected?
since it is less common in females, an affected female is more likely to have affected offspring. male offspring are more likely to be affected than female offspring
which sex has higher rates of NTD?
females
what increases the risk for NTD the most?
having 2+ children already affected
what are susceptibility genes?
genes that predispose to a common disease but do NOT independently cause the disease to occur
characterize monogenic, multifactorial and infectious diseases
monogenic- mostly genes
multifactorial- 50/50 genes and environment
infectious- mostly environment
what is MODY?
rare, inherited form of DM caused by defects in insulin secretion, onset in early 20s, not assoc with obesity, autosomal dominant, 11 subtypes
what mitochondrial disorders involve DM? why?
MELAS, Kearns-Sayne syndrome, diabetes and hearing loss; mitochondrial d/o often affect pancreas bc it has high energy requirement
what are the causes of most cases of DM1, DM2?
combo of genes and environment
what genes are involved with early-onset alzheimer’s?
PS1, PS2, APP
what is the inheritance pattern of Alzheimer’s caused by PS1, PS2, APP?
Mendelian
autosomal dominant
what are the features of early-onset alzheimer’s?
onset between 40-50
100% penetrance
what genes are implicated in multifactoral alzheimer’s disease?
APOE (esp E4 allele)
which APOE allele is protective?
E2
what is the highest risk genotype for multifactoral alzheimer’s disease?
homozygous for E4
highest risk for females with this genotype- lifetime risk 60%
what yields the highest genetic risk for schizophrenia or bipolar d/o?
being the child of 2 affected individuals
what are other genetic conditions that are assoc with bipolar d/o?
fragile X, 22q11 deletion
what is concordance? discordance?
concordance- twins share same trait
discordance- twins do not share trait
what is concordance rate for MZ vs DZ twins?
MZ= 1 DZ = 0.5
what can be used to determine the heritability of a trait?
evaluating the difference between concordance in MZ vs. DZ twins (greater concordance in MZ twins vs. DZ twins is stronger evidence for genetic component)
what is the equation used to calculate concordance
h = 2 (cMZ -cDZ)
what are the 2 limitations of twin studies?
1- environment for MZ and DZ twins are assumed to be similar
2- somatic mutation can occur in one MZ twin and thus the twins might not be quite genetically identical
what is the basis for adoption studies?
assume similarities between adoptees and adoptive parents are due to environment
what are the limitations of adoption studies (3)?
1- prenatal environmental influences
2- late adoptions
3- placement with another family member
