Genetic dissection of complex traits with chromosome substitution strains of mice.
Chromosome substitution strains (CSSs) have been proposed as a simple and powerful way to identify quantitative trait loci (QTLs) affecting developmental, physiological, and behavioral processes. Here, we report the construction of a complete CSS panel for a vertebrate species. The CSS panel consists of 22 mouse strains, each of which carries a single chromosome substituted from a donor strain (A/J) onto a common host background (C57BL/6J). A survey of 53 traits revealed evidence for 150 QTLs affecting serum levels of sterols and amino acids, diet-induced obesity, and anxiety. These results demonstrate that CSSs greatly facilitate the detection and identification of genes that control the wide diversity of naturally occurring phenotypic variation in the A/J and C57BL/6J inbred strains.
Singer
Jonathan B
JB
Broad Institute, Cambridge, MA 02142, USA.
Hill
Annie E
AE
Burrage
Lindsay C
LC
Olszens
Keith R
KR
Song
Junghan
J
Justice
Monica
M
O'Brien
William E
WE
Conti
David V
DV
Witte
John S
JS
Lander
Eric S
ES
Nadeau
Joseph H
JH
D000596:Amino Acids / Q000097:blood; D000818:Animals; D001007:Anxiety / Q000235:genetics; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D013261:Sterols / Q000097:blood; D015430:Weight Gain
D000596:Amino Acids; D013261:Sterols