BIN300 -W3 Design of QTL mapping experiments

linkage marker -QTL gene

many similariteis, differentL WTL genotyp is not observed, try to infer QTL genotype from phenotype

old markers

protein polymorphisms, might have an effect on trait

new markers: RFLP, microsatellitles, SNP

Unlikely to have effect on trait

population wide LD mapping (additive effect a)

Linkage disequilibrium (LD)

alleles at locus 1 are non-randomly associated with alleles at locus 2

D is difference between observed haplotypes

R2 standardized measure

D=0, are in linkage equilirbium, not 0 in LD

R2 = 0, no LD, R2 is 1, perfect LD, one ALLELE can predict other

WTL genotypes and values

QQ: m+a (m=mean = effect of all other QTL)

Qq: m+

• no dominance, d=0, complete dominance d=a

• qq: m-a

d

Means of marker genotypes

difference between homozygotes

D=r*u-s*t

D=0 → no effect of genotypes

D=1 → full effect of marker genotypes

Significant difference: could be gene or linked marker

marker has effect if D does not equal 0

marker = gene

recent mutation, random drift, selection, or migration

recombinaiton reduces D

Dt=D0 (1-Ɵ)^t

• Ɵ small Dt (still) large

• need dense marker map

  • D0 large, crosses between lines

QTL dtection in crosses between inbred lines

F1 animals are heterozygous, complete LD, QTL and marker freqs = 0.5, linakge phase is as in parents

The back-cross design

M1Q1/M2Q2 * M2Q2/M2Q2

The F2- design

M1A1/M2Q2 * M1Q1/M2Q2

M1M1-M2M2 = 2(1-Ɵ)A

size of QTL effect: a

distance from marker till QTL

a and Ɵ cannot be disentangled, although maximum likelihood can, but power is lown

no fixation at QTL/marke

marker fixed/QTL not

marker and QTL not fixed, in terms of D

reduction of LD

coupling phase: M1Q1/M2Q2

• M1Q2 with freq ½ Ɵ, i.e. reduction of M1Q1 haplo of 1/2Ɵ

repulsion phase: M1Q2/M2Q1

• M1Q1 with freq 1/2Ɵ, i.e. increase of M1Q1 haplo of ½ Ɵ

chan

change in freq M1Q1

1/2Ɵ [freq{repulsion)-freq(coupling)]=

freq M1Q1 in F3 and FTS

LD as a function of time and Ɵ

crosses of inbred lines

useful in plants and lab animals

in animals approximate by wildboar*largewhite

useful for detecting QTL

is QTL also segregating within population?

is +allele always present in largewhite?