Multifactorial: Lect 19

Question 1

Single gene

Answer 1

• determined by the alleles at a single locus
• characterized by their patterns of transmission in families (AD, AR, XL D/R)
• chrom abnormalities
• mitochondrial
• ex: SCA, CF, DMD

Question 2

Multifactorial/complex

Answer 2

• genes + environment
• congenital malformations
• acquired diseases of childhood and adult life that don’t display clear menedlian pattern of inheritance but show familial aggregation.
• majority of diseases in human popuations.
• don’t produce discrete phenotype/genotype
• due to more than one gene affecting the trait
• additive or non-additive alleles

Question 3

Polygenic

Answer 3

• mutations or variants in more than one gene contribute to the trait.
• ex: multiple genes affecting ht. = nl or Gaussian distribution.

Question 4

Continuous phenotype

Answer 4

• number of genes controlling the trait determine the extent of phenotypes observed.
• more genes = broader range of phenotype

Question 5

Liability/threshold model:

• Liability:
• Threshold:

Answer 5

• describes a population’s genetic and environmental susceptibility
• used to identify recurrence risk in families.
• all factors that contribute to the disease = liability
• quantitative variable to cause expression of abnl phenotype.

Question 6

Familial relative risk:

Answer 6

• the more closely related you are to someone w/ a complex disorder, the more likely you are to have some of the same alleles.
• risk drops by half for every degree distance from affected person.

Question 7

Familial aggregation and relative risk

Answer 7

-measured by comparing the freq. (prevalence) of the disease in relatives of an affected proband w/ its freq. in the general population.

• the larger the λr, the greater the fam. aggregation.
• increase in heritability = incr genetic contribution.

Question 8

Liability threshold model:

Answer 8

• risk of recurrence is higher in relatives of severely affected indiv.
• recurrence risk is high in close relatives and decreases rapidly in more distant relations.
• incr. risk if more than one close relative is affected
• in sex biased traits (ex. pyrloric stenosis more common in males)

Question 9

Pyloric stenosis

Answer 9

males are more prone and have a lower liability threshold

• the children/siblings of an affected female are more at risk of having the condition
• her sons/brothers are more at risk than daughters/sisters.

Question 10

Multifactorial inheritance examples?

Answer 10

-Anencephaly and Spina bifida

Question 11

Tools for determing genetics vs. environment

Answer 11

• population/migration studies: indicative of environmental factors (ex: breast cancer low in Asian women but after immigrating to the US, increase in incidence)
• family studies: similar to twin but not as precise. “more genetic variability”
• twin studies
• adoption studies: separation of identical twins = same genes but diff envir.
• assoc. studies: to test the co-occurrence of a specific allele at a marker locus and a trait in population by comparing the freq. of an allele in pts and controls. Don’t analyze familial inheritance patterns.

Question 12

Twins:

Monozygotic:

Dizygotic:

Answer 12

• derived from a single ovum
• genetically identical except mitochondrial.
• from two ovas but share intrauterine envr.
• 50% identical (siblings)

Question 13

Concordance:

Discordance:

Answer 13

-both twins have the same disease.
-If concordance = 100% then disorder is genetically determined
If concordance is less than 100% then non-genetic factors are involved.

Discordance: one twin has it but the other doesn’t
-The greater discordance = the greater environmental input

Question 14

Limitations of twin studies

Answer 14

• underestimate heritability
• MZs have different genes (mitochondrial) and epigenetic differences.
• different environmental exposures
• diff genes in diff twin pairs
• ascertainment bias