Multifactorial Disorders (4)

Question 1

Mendelian

Answer 1

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

Question 2

Complex

Answer 2

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

Question 3

Polygenic

Answer 3

The result of the action of multiple genes

Question 4

Multifactorial

Answer 4

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

Question 5

Familial clustering

Answer 5

λs (relative risk to 2nd sibling)

Question 6

Schizophrenia

Answer 6

Inherited, but not mendelian

Question 7

Phenotypes are determined

Answer 7

by action of may genes at different loci

Question 8

Polygenic/complex/multifactorial inheritance

Answer 8

• Genes are additive (not recessive/dominant)
• Blood pressure, head circumference, height, intelligence
• Gaussian distribution (normal)
• Influenced by environment

Question 9

Congenital malformations with multifactorial inheritance

Answer 9

Cleft lip/palate, congenital hip dislocation, congenital heart defects, neural tube defects, pyloric stenosis, talipes/club foot

Question 10

Acquired diseases of childhood & adult life with multifactorial inheritance

Answer 10

Asthma, autism, cancer, diabetes mellitus, epilepsy, glaucoma, hypertension, inflammatory bowel disease (Crohn disease), ischaemic heart disease & stroke, bipolar disorder, multiple sclerosis, Parkinson disease, psoriasis, rheumatoid arthritis, schizophrenia

Question 11

NTDs prevented by

Answer 11

400ug/day of maternal folic acid supplementation 1-3 months in pregnancy (50-70% prevention)

Question 12

SNPs

Answer 12

• Single nucleotide polymorphism
• Common, usually binary
• Easy and quick to test (computer)
• Change in one single nucleotide

Question 13

How many SNPs identified?

Answer 13

> 10 milion

Question 14

Population association studies and linkage disequilibrium

Answer 14

• Most disease bearing chromosomes are descended from ancestral chromosomes
• Can detect association to

Question 15

Alzheimer’s

Answer 15

Inheriting susceptibility rather than the condition

Question 16

What age does Alzheimer’s effect?

Answer 16

Most common form of dementia >40 years

Question 17

Symptoms of Alzheimer’s

Answer 17

Inability to cope, loss of memory, brain damage

Question 18

Neurology of Alzheimer’s

Answer 18

Shrinkage of brain, tangles of B-amyloid protein in nerve fibres of hippocampus

Question 19

Familial clustering of Alzheimers

Answer 19

3 to 10

Question 20

Much of the effect of Alzheimers is due to the gene…

Answer 20

Api-Lipoprotein E (APOE) - APOEE2, APOEE3 and APOE*E4

Question 21

*E4 halotype confers

Answer 21

Increase in susceptibility (affected much earlier if homozygote E4/E4)

Question 22

*E2 halotype confers

Answer 22

A protective effect

Question 23

Age-related Macular Degeneration

Answer 23

• Leading cause of irreversible central visual dysfunction caused by degeneration of the macula
• Early deposition of drusen

Question 24

Major genetic effects for AMD

Answer 24

CFH (1q), ARMS2 (10q)

Question 25

Major environment effect on AMD

Answer 25

Smoking

Question 26

Genetic and smoking major effects increase risk for AMD by how much?

Answer 26

70 fold