1. QTL Mapping in Humans Lon Cardon, Stacey Cherny Goncalo Abecasis
University of Oxford
Goncalo Abecasis
University of Michigan
Pak Sham
Institute of Psychiatry, King’s College, London

2. 3 Stages of Genetic Mapping
Are there genes influencing this trait?
Epidemiological studies
Where are those genes?
Linkage analysis
What are those genes?
Association analysis

3. 3 Stages of Genetic Mapping
Are there genes influencing this trait?
Epidemiological studies
Where are those genes?
Linkage analysis
What are those genes?
Association analysis

4. Polygenic Traits 1 Gene 2 Genes 3 Genes 4 Genes
 3 Genotypes
 3 Phenotypes
2 Genes
 9 Genotypes
 5 Phenotypes
3 Genes
 27 Genotypes
 7 Phenotypes
4 Genes
 81 Genotypes
 9 Phenotypes
QTL mapping: identify specific loci
SEM work this week

5. QTL Linkage Analysis
Aim: Identify regions of genome that contain (‘are linked with’) gene(s) influencing trait
Follows directly from biometrical model
Builds on all concepts developed this week
Twins informative, as are extended sibships  larger kindreds
Only one new data type added to design: genotypes
‘identity by descent’ derived from genotypes

6. E E C C A A Q Q rMZ = rDZ = 1 rMZ = 1, rDZ = 0.5 ^ rMZ = 1, rDZ =  e
Twin 1 trait
Twin 2 trait

7. Some QTL linkage analysis software programs
ACT: Chris Amos’ variance components suite
Genehunter: Leonid Kruglyak’s discrete-trait package, extended to simple VC
SOLAR: John Blangero’s variance components package
QTDT/Merlin: Goncalo Abecasis’ association/linkage VC program and likelihood engine
Many others, large and small
Mx: Mike Neale’s variance components program

8. Friday afternoon schedule
1:30-2:30: Linkage analysis theory: Abecasis/Sham
2:30-3:00: QTL linkage analysis in Mx: Cardon/Cherny
3:00-3:30: Tea
3:30-4:00: Multivariate QTL linkage analysis: Cardon/Cherny
4:00-4:45: Beyond linkage: some current issues in QTL identification (aka: gratuitous promotion of advanced workshop): Cardon