Multifactorial Inheritance

Question 1

Multifactorial traits

Answer 1

. Continuous (quantitative) or discontinuous (dichotomous) depending on presentation in population
. Discontinuous traits can display variability in their presentation, but are thought of as absent or present

Question 2

Continuous multifactorial traits

Answer 2

. Quantifiable characteristics (height, weight, bp)

.

Question 3

Genetic factors for hypertension

Answer 3

. Contribute 30-50% to developing hypertension
. Variant forms of 43 genes assoc w/ bp or hypertension
. AGT, ULK4, SlC39AB, EBF1, CYP11B2, ATP2B1

Question 4

Environmental factors in developing hypertension

Answer 4

. sodium 
. Exercise
. Smoking
. Obesity
. Alcohol
. Ca

Question 5

Multifactorial threshold traits

Answer 5

. There is an underlying “liability” distribution in population
. Individuals on low end of liability distribution have few genetic variants and environmental factors contributing to development of trait, low disease risk
. There is threshold level of liability that has to be attained before the disease manifests

Question 6

Liability

Answer 6

. All of the genetic and environmental factors that may contribute to development of a multifactorial disorder

Question 7

Consequences of threshold model of multifactorial disorders for recurrence risk

Answer 7

. Recurrence risk higher among relative of severely affected patients than loss of less affected
. Risk greatest among 1st-degree relatives and dec. rapidly among 2nd and 3rd degree bc there is less shared genes
. If there is more than 1 close relative affected, the risk for other relatives is inc.
. If condition is more common in individuals of 1 sex, the relates of an affected person of the less frequently affected sec will be a tighter risk than relatives of affected person of the more frequently affected sex

Question 8

Pyloric stenosis

Answer 8

. Most common cause of intestinal obstruction (2-4 infants/1000 live births)
. Pyloric sphincter muscle cell hypertrophy prevents emptying of stomach into duodenum
. Infants present at 204 weeks w/ projectile vomiting, persistant hunger, stomach contraction, dehydration, failure to thrive
. Inherited in multifactorial manner w/ genetic and environmental risk factors
. 5 times more common in males

Question 9

Risk of recurrence among offspring and siblings of affected individual

Answer 9

Sq rt of incidence in general population

Question 10

Heritability

Answer 10

. Developed to assess the extent to which particular trait is genetically determined
. Higher than heritability, the more important genetic factors are in development of the trait
. Measured by comparing data on concordance for trait in monozygotic and dizygotic twins
Heritability = 2(Cmz - Cdz)
. If environmental, concordance is same in both twin sets so heritability approaches 0
. If genetic: concordance in MZ wins approaches 1 and DZ twins approaches 0.5
. Heritability ranges from 0 to 1

Question 11

Neural tube defects

Answer 11

. Result from failure of neural tube to close
. Result from genetic and environmental factors
. Recurrence risk is higher w/ presence of affected siblings
. Major forms of defects are caused by similar factors, recurrence risk for 1 form of NTD is inc. by occurance of another
. 80 genes important for developing it: protein codling, methylation rxns, nucleotide biosynthesis, Folate transport, glucose metabolism, cell adhesion, oxidant stress
. Folic acid consumption dec. incidence

Question 12

Common multifactorial diseases of adulthood

Answer 12

. Cardiovascular disease
. Cancer
. DM
. Alzheimer’s 
. Obesity
. Alcoholism
. Psych disorders