Non-Medelian: Multifactorial inheritance Flashcards
(10 cards)
Multifactorial Inheritance
Combined contribution of genes and environmental factors in the causation of a particular disease or trait
- Considerable variation in severity and expression of the phenotype
- Gender difference in the frequency of occurrence
Multifactorial Traits
Quantitative Traits- measured on a numerical scale; tend to follow ‘bell-shaped’ distribution in populations (i.e. height, weight, and BP)
Threshold Traits- Either present or absent. A bell-shaped distribution in the population with respect to liability to a trait, and only those individuals exceeding the threshold on the liability scale will actually exhibit the trait (i.e. club foot, diabetes, cleft lip, and pyloric stenosis)
Liability
- Total combined genetic and environmental factors that influence the development of a multifactorial disorder or trait
- Cannot be measured; determined from the incidence of the disease in a group using statistics of the normal distribution
Recurrence risk for common birth defects
~4%
Recurrence Risk
The likelihood that a trait or disorder present in one family member will occur again in other family members in the same or subsequent generations
-Multifactorial traits have a recurrence risk less than that of single gene disorders, but are not insignificant.
Recurrence Risk Rules for MF inheritance
- The greater the severity, the higher recurrence
- Recurrence risk is higher if more than one family member is affected
- Decreases rapidly in more remotely related individuals
- Greater if the pro band is of the less commonly affected sex
- For first degree relatives it is approximately the square root of the population incidence of the trait
Heritability
Measure of the fraction of the total phenotypic variance of a trait in a population that is caused by genes; this value lies between 0 and 1
-Evidence of genetic contribution to a disorder comes from;
observations of familial aggregation and twin studies (comparing concordance rate of monozygotic twins vs dizygotic twins)
Heritability= (MZ concordance - DZ concordance) x 2
Concordance Rate = # of all concordant pairs/ # of all twin pairs.
i.e. when 100% genetic MZ = 1 and DZ = 0.5 so Heritability=1
Linkage Analysis
- Used to determine whether the inheritance of a genetic marker predisposes to a particular disease/trait in a family
- Goal is to find a region of the genome where a candidate disease allele could be found
Linkage Analysis: Steps
- Determine how far apart the loci are by calculating recombination frequency
- Assess the strength of evidence for linkage by calculating the LOD score
Association Studies
To identify specific alleles for a particular disease/trait within an already designated gene region
-Hypothesis is that a particular allele occurs more frequently in individuals with the disease than in controls