Multifactorial Disease

Question 1

Define Mendelian

Answer 1

Obeys Mendel’s laws of segregation- dominant, recessive, X-linked

Question 2

Define complex

Answer 2

Tends to be used vaguely to describe something with an inherited but non-mendelian component

Question 3

Define polygenic

Answer 3

The result of the action of multiple genes

Question 4

Define multifactorial

Answer 4

The result of multiple factors, usually including both genetic & environmental

Question 5

Does a multifactorial disease have a genetic component?

Answer 5

• Familial clustering

- Twin studies

Question 6

What are problems with twin studies?

Answer 6

• Assumption that the degree of environmental sharing is the same for MZ twins- difference in birth weights, variation in time of splitting of the early embryo
• DZ twins can share more than half their genes

Question 7

What congenital malformations show multifactorial inheritance

Answer 7

• Cleft lip/palate
• Congenital hip dislocation
• Congenital heart defects
• Neural tube defects
• Pyloric stenosis
• Talipes

Question 8

What acquired disease of childhood & adult life show multifactorial inheritance?

Answer 8

• Asthma
• Autism
• Cancer
• Diabetes mellitus
• IDB
• Schizophrenia
• Parkinson disease

Question 9

What is the likelyhood of a disease with a high magnitude of effect and high frequency in the population?
A disease with low magnitude of effect and frequency

Answer 9

High= unlikely to exist
Low= function studies

Question 10

What do genetic association studies look for?

Answer 10

• Seek to relate variation in human DNA sequence with a disease or trait
• Provides greater power to detect common genetic variants conferring susceptibility to complex phenotypes
• Estimates population attributable risk
• Controls should match cases and be a representative sample of the population

Question 11

Describe the genetics of Alzheimer’s disease

Answer 11

• Sequence variants at a polymorphic locus have a large effect on age of onset
• Missense mutation in APP
• Much effect due to a gene implicated in heart disease- app-lipoprotein E (APOE) 3 haplotypes

Question 12

What are the 3 haplotyes for alzheimer’s disease?

Answer 12

E4 = Increase in susceptibility
E2= Protective effect
E4/E4= Homozygous effected earlier than heterozygous
-Risk is increased further if there is high blood pressure

Question 13

What are the risks for AMD?

Answer 13

• Genetics= CFH, ARMS2

- Environmental= smoking