Segregation analysis Flashcards
what is this, mendelial or complex trait if…
- rare
- single gene
- severe mutaion
- large phenotypic effect
Mendelian
what is thi? if the characteristics are
- common
- many genes
- mild mutaitons
- small phenotypic effect
*
name some susceptibility genes
- BRCA1 (same)
- BRCA2 (breast, ovarian, prostate cancer)
- colorectal cancer APC,MYH and others
an example of genes that modify severity?
in sickle cell (mild vs severe)
example of modifiers of response to a drug?
alternative cytochrome P450 (can increase effect of b-blockers)
what is genetic epidemiology?
the study of how and why diseases cluster in families
also answers if disease is due to enviromental exposures or genetics
what is:
- aggregation studies
- twin studies and adoption studies
- segregation analysis
- linkage studies
- fine mapping
- candidate gene studies
- 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
when can you say that there is evidence of familial aggregation?
how do oyu calculate risk?
- 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
Risk Ratio Examples
remember the formula
risk of disease in relatives of proband / risk in population
cystic fibrosis 0.25 / 0.0004 = 500
who to do twin studies?
- 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
what is the purpose of SA segregation analysis?
- study how disease is transmitted
- determine if AD, AR, x-linked
- determine is there is evidence of gene effect
what is linkage?
- its statistical method to map genes
- violation of mendels law
- its the tendency of 2 or more loci to segregate together in a family