QTL Mapping in Humans

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QTL Mapping in Humans

• Lon Cardon, Stacey Cherny
• University of Oxford
• Goncalo Abecasis
• University of Michigan
• Pak Sham
• Institute of Psychiatry, Kings College, London

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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

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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

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Polygenic Traits
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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

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rMZ rDZ 1
rMZ 1, rDZ 0.5
E
E

rMZ 1, rDZ ?
C
C
e
e
A
A
c
c
a
a
Q
Q
q
q
Twin 1 trait
Twin 2 trait
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Some QTL linkage analysis software programs

• ACT Chris Amos variance components suite
• Genehunter Leonid Kruglyaks discrete-trait
  package, extended to simple VC
• SOLAR John Blangeros variance components
  package
• QTDT/Merlin Goncalo Abecasis
  association/linkage VC program and likelihood
  engine
• Many others, large and small
• Mx Mike Neales variance components program

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Friday afternoon schedule

• 130-230 Linkage analysis theory
  Abecasis/Sham
• 230-300 QTL linkage analysis in Mx
  Cardon/Cherny
• 300-330 Tea
• 330-400 Multivariate QTL linkage analysis
  Cardon/Cherny
• 400-445 Beyond linkage some current issues
  in QTL identification (aka gratuitous promotion
  of advanced workshop) Cardon