Segregation analysis

Question 1

what is this, mendelial or complex trait if…

• rare
• single gene
• severe mutaion
• large phenotypic effect

Answer 1

Mendelian

Question 2

what is thi? if the characteristics are

• common
• many genes
• mild mutaitons
• small phenotypic effect
  *

Question 3

name some susceptibility genes

Answer 3

• BRCA1 (same)
• BRCA2 (breast, ovarian, prostate cancer)
• colorectal cancer APC,MYH and others

Question 4

an example of genes that modify severity?

Answer 4

in sickle cell (mild vs severe)

Question 5

example of modifiers of response to a drug?

Answer 5

alternative cytochrome P450 (can increase effect of b-blockers)

Question 6

what is genetic epidemiology?

Answer 6

the study of how and why diseases cluster in families

also answers if disease is due to enviromental exposures or genetics

Question 7

what is:

• aggregation studies
• twin studies and adoption studies
• segregation analysis
• linkage studies
• fine mapping
• candidate gene studies

Answer 7

• aggregation studies evidence of clustering disease in family?
• twin studies and adoption studies genetic or enviromenta?
• segregation analysis is there a GENE? AD? AR?
• linkage studies where are the genes located?
• fine mapping & candidate gene studies exact location and polymorphisms

Question 8

when can you say that there is evidence of familial aggregation?

how do oyu calculate risk?

Answer 8

• when the incidence of disease is higher in the relatives than in controls
• family hx of disease
• a higher % cohort with family hx develop disease
• calculate
  
  • recurrence risk ration
  • risk of disease in probands/ risk in population
  • risk of disease in relatives of proband / relatives of controls

Question 9

Risk Ratio Examples

remember the formula

risk of disease in relatives of proband / risk in population

Answer 9

cystic fibrosis 0.25 / 0.0004 = 500

Question 10

who to do twin studies?

Answer 10

• for a mendelian disease
• with complete penetrance
• monozygotic
• dizygotic
• if MZ have higher concordance than DZ then is genetic effect

ASK the questio when one twin is affected how often is th eother affected?

if MZ=DZ then might be enviroment

Question 11

what is the purpose of SA segregation analysis?

Answer 11

• study how disease is transmitted
• determine if AD, AR, x-linked
• determine is there is evidence of gene effect

Question 12

what is linkage?

Answer 12

• its statistical method to map genes
• violation of mendels law
• its the tendency of 2 or more loci to segregate together in a family