Diseases with Complex Patterns of Inheritance Flashcards
How does the frequency of disorders with multifactorial inheritance compare to the frequency of disorders due to genome/chromosome mutations and single-gene mutations?
Disorders with multifactorial inheritance are much more prevalent (50 per 1000 births) than genome mutations (6 per 1000 births) and single gene mutations (10 per 1000 births)
What are the major differences between Mendelian and complex traits and their inheritance?
Mendellian traits are qualitative or dichotomous, whereas complex traits can be either continusous (quantitative) or qualitative
Mendelian traits almost always attributable to different alleles of single genes whereas complex traits result from the contributions of multiple genes with or without environment influences
Mendelian inheritance rules are simply calculated for family members, but complex traits require empirically derived risk tables
What statistical distribution decribes quantitative traits.
A gaussian distribution (normal distribution, shaped like a bell curve)
2 standard deviations from the mean in either direction includes 95% of the population
What is the polygenic theory of discontinuous traits?
A gaussian distribution of suscetibilty for disease exists with a certain threshold above which individuals will have a high susceptibility for disease
How is a relative risk ratio calculated
(Prevalence of disease in relatives of an affected person)/(Prevalence of disease in the general population)
Values >> 1 suggest genes contribute to the disease
What confounding factor may complicate interpretations of relative risk ratios in families with complex genetic traits?
Family members often share environmental factors which may contribute to disease expression or severity
It is difficult to separate the effects of environment from genetic effects
Describe the setup of case control studies
A comparison of the frequency of a disease in an extended family to that of a control family
Example: Siblings of MS patients have a higher frequency of also having MS than siblings of the MS patients’ spouses
How does the percentage of alleles in common with the proband differ in: monozygotic twins, first degree relatives, second degree relatives, and third degree relatives?
MZ: 100%
1st degree: 50%
2nd degree: 25%
3rd degree: 12.5%
True or false: complex traits will have monozygotic concordance rates equal to 100%
False.
Complex traits will have monozygotic concordance rates less than 100% due to factors other than genes contributing to a disease
What can be concluded if the concordance rate is higher for monozygotic twins than dizgotic twins?
Genetics are involved
Because environment is often similar for twins, genetics must be responsible for much of the observed differences
Given variance due to genes and variance due to environment, how is the variance of a quantitative property calculated?
Variances are additive when they are due to different causes
vp = ve + vg
What is heritability and how is it calculated?
The proportion of the total variance that is due to genes
h2 = vg/(ve+vg)
h2 = (variance in DZ pairs - variance in MZ pairs)/Variance in DZ pairs
In digenic retinitis pigmentosa, what genotype do affected individuals have?
Digenic = two genes contribute to the presence of disease
A mutant allele in each gene is required for the disease to be expressed
Describe the shared alleles in Hirschsprung disease.
3 major loci have been identified as related to Hirschsprung disease
Most affected individuals have mutations in all three loci, but others have the same phenotype but mutations in only two of the three loci
In type 1 diabetes, similarities in what gene locus between an affected individual and their siblings increase the risk of diabetes in the siblings?
Genes of the major histocompatibility complex (MHC) on chromosome p6
The DR haplotypes of the MHC gene determine the risk of type I diabetes in the sibling. If they share no DR haplotypes, then the risk is 1%, but the risk is increased if they share one (5%) or two (17%)
