Non-Medelian: Multifactorial inheritance

Question 1

Multifactorial Inheritance

Answer 1

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

Question 2

Multifactorial Traits

Answer 2

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)

Question 3

Liability

Answer 3

• 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

Question 4

Recurrence risk for common birth defects

Answer 4

~4%

Question 5

Recurrence Risk

Answer 5

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.

Question 6

Recurrence Risk Rules for MF inheritance

Answer 6

1. The greater the severity, the higher recurrence
2. Recurrence risk is higher if more than one family member is affected
3. Decreases rapidly in more remotely related individuals
4. Greater if the pro band is of the less commonly affected sex
5. For first degree relatives it is approximately the square root of the population incidence of the trait

Question 7

Heritability

Answer 7

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

Question 8

Linkage Analysis

Answer 8

• 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

Question 9

Linkage Analysis: Steps

Answer 9

1. Determine how far apart the loci are by calculating recombination frequency
2. Assess the strength of evidence for linkage by calculating the LOD score

Question 10

Association Studies

Answer 10

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