F2 population

x

Progeny testing

x

QTL

QTL

QTL

QTLE

ffect

of g

enot

ype

Location of recombination

QTL

QTL

QTL

QTLE

ffect

of g

enot

ype

Location of recombination

position (cM)44 46 48 50 52 54 56 58

Effe

ct o

f gen

otyp

e

-0.2

-0.1

0.0

0.1

0.2

0.3

0.4

0.5

position (cM)

44 46 48 50 52 54 56 58

Effe

ct o

f gen

otyp

e

-0.2

-0.1

0.0

0.1

0.2

0.3

0.4

0.5

Progeny testing

x

Oliver et al. 2005PLoS Biol 3(5): e135

Single QTL

Christians et al. 2006 Genetics 173: 1547–1553

Multiple QTL

Alternative approaches

• Recombinant inbred lines (RIL)

Recombinant inbred lines (by sibling mating)

From www.complextrait.org/Powerpoint/ctc2004/karl_broman.ppt

Recombinant inbred lines(by selfing)

From www.complextrait.org/Powerpoint/ctc2004/karl_broman.ppt

Recombinant inbred lines

• Only have to genotype each line once• Can phenotype multiple individuals per

genotype• Can measure multiple phenotypes• Different environments• A number of RILs already available, e.g.,

WebQTL http://www.genenetwork.org/home.html

The “Collaborative Cross”

From www.complextrait.org/Powerpoint/ctc2004/karl_broman.ppt

Genome of an 8-way RI

From www.complextrait.org/Powerpoint/ctc2004/karl_broman.ppt

Alternative approaches• Recombinant inbred lines• Collaborative cross• Heterogeneous stocks – like collaborative

cross, but not inbred• Microarrays combined with QTL• Expression QTL

Expression QTL• How often is regulation cis vs. trans?, e.g.,

Ronald et al. 2005 PLoS Genet 1(2): e25.• Mapping “cluster regulators”

Yvert et al. 2003, Nature Genetics 35: 57-64

• How often is regulation cis vs. trans?• Mapping “cluster regulators”/ networks

Chesler et al. 2005, Nature Genetics 37: 233-242

• Mapping expression networks and behaviour

Chesler et al. 2005, Nature Genetics 37: 233-242

Alternative approaches• Recombinant inbred lines• Collaborative cross• Heterogeneous stocks – like collaborative

cross, but not inbred• Microarrays combined with QTL• Expression QTL• In silico methods

In silico methods• Use already-available phenotypes from

many inbred lines• Associate with marker data, e.g., Pletcher

et al. (2004 PLoS Biol 2(12): e393) typed many new SNPs

• Associate with haplotypes, not individual marker genotypes

Strain Marker A Marker B Marker C Marker D Marker E Marker F

1 A T A G A T

2 G T A G G G

3 C T A G C A

4 T T G C T C

5 A A G C T T

In silico methods• Use already-available phenotypes from

many inbred lines• Associate with marker data, e.g., Pletcher

et al. (2004 PLoS Biol 2(12): e393) typed many new SNPs

• Associate with haplotypes, not individual marker genotypes

Strain Marker A Marker B Marker C Marker D Marker E Marker F

1 A T A G A T

2 G T A G G G

3 C T A G C A

4 T T G C T C

5 A A G C T T

In silico methods• Use already-available phenotypes from

many inbred lines• Associate with marker data, e.g., Pletcher

et al. (2004 PLoS Biol 2(12): e393) typed many new SNPs

• Associate with haplotypes, not individual marker genotypes

• In addition, can look for concordance of QTL location between different crosses, different species (!) (Burgess-Herbert 2008; Genetics 180: 2227–2235)