Dissection of complex adult traits in a mouse synthetic population

Genome Research
David T BurkeAndrzej T Galecki

Abstract

Finding the causative genetic variations that underlie complex adult traits is a significant experimental challenge. The unbiased search strategy of genome-wide association (GWAS) has been used extensively in recent human population studies. These efforts, however, typically find only a minor fraction of the genetic loci that are predicted to affect variation. As an experimental model for the analysis of adult polygenic traits, we measured a mouse population for multiple phenotypes and conducted a genome-wide search for effector loci. Complex adult phenotypes, related to body size and bone structure, were measured as component phenotypes, and each subphenotype was associated with a genomic spectrum of candidate effector loci. The strategy successfully detected several loci for the phenotypes, at genome-wide significance, using a single, modest-sized population (N = 505). The effector loci each explain 2%-10% of the measured trait variation and, taken together, the loci can account for over 25% of a trait's total population variation. A replicate population (N = 378) was used to confirm initially observed loci for one trait (femur length), and, when the two groups were merged, the combined population demonstrated increased power...Continue Reading

References

Nov 1, 1990·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·J L KuhnG Jesion
Feb 1, 1989·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·L A FeldkampM Kleerekoper
Dec 30, 1999·Nature Genetics·J A BeckE M Fisher
Nov 6, 2004·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Ruth LipmanRichard A Miller
Apr 2, 2005·Nature Reviews. Genetics·Jonathan FlintRichard Mott
Jun 20, 2006·Physiological Genomics·Philip HanlonDavid T Burke
Jul 13, 2006·Nature Genetics·William ValdarJonathan Flint
Aug 5, 2006·Genetics·William ValdarJonathan Flint
Dec 19, 2006·Nature Reviews. Genetics·Luanne L PetersKaren L Svenson
May 12, 2007·Physiology & Behavior·Danielle R ReedMichael G Tordoff
Sep 1, 2007·Nature Cell Biology·Nadia Rosenthal, Steve Brown
Feb 8, 2008·Genome Research·Toyoyuki TakadaToshihiko Shiroishi
Mar 28, 2008·Nature·Günter P WagnerJames M Cheverud
Apr 10, 2008·Nature Reviews. Genetics·Mark I McCarthyJoel N Hirschhorn
Apr 24, 2008·Genetics·Jane P Kenney-HuntJames M Cheverud
Aug 16, 2008·Epidemiology·Peter Kraft
Aug 22, 2008·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Elissa J CheslerKenneth F Manly
Nov 7, 2008·Nucleic Acids Research·Stephen C GrubbMolly A Bogue
Dec 17, 2008·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Karl J JepsenJoseph H Nadeau
Apr 17, 2009·The New England Journal of Medicine·John Hardy, Andrew Singleton
Apr 17, 2009·The New England Journal of Medicine·David B Goldstein
May 5, 2009·Genome Research·Jonathan Flint, Trudy F C Mackay
May 13, 2009·Nature Reviews. Genetics·Johannes BeckersMartin Hrabé de Angelis
Jan 16, 2010·American Journal of Human Genetics·Rita M CantorJanet S Sinsheimer
Mar 20, 2010·Journal of Human Genetics·Chee Seng KuKee Seng Chia
Jun 22, 2010·Nature Genetics·Jian YangPeter M Visscher
Nov 6, 2010·Nucleic Acids Research·Judith A BlakeMouse Genome Database Group

Citations

Oct 10, 2012·Nature Reviews. Genetics·Jonathan Flint, Eleazar Eskin

Related Concepts

Chimera Organism
Chromosomes
Crosses, Genetic
Trochanter
Genetics, Population
Mice, Inbred BALB C
Mice, Inbred C57BL
Recombination, Genetic
Bone Structure of Spine
Variation (Genetics)

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