Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice.
The genetic basis of variation in obesity in human populations is thought to be owing to many genes of relatively small effect and their interactions. The LG/J by SM/J intercross of mouse inbred strains provides an excellent model system in which to investigate multigenic obesity. We previously mapped a large number of quantitative trait loci (QTLs) affecting adult body weight in this cross. We map body composition traits, adiposity, and skeletal size, in a replicate F2 intercross of the same two strains containing 510 individuals. Using interval-mapping methods, we located eight QTLs affecting adiposity (Adip1-8). Two of these adiposity loci also affected tail length (Adip4 and Adip6) along with seven additional tail length QTLs (Skl1-7). A further four QTLs (Wt1-4) affect adult weight but not body composition. These QTLs have relatively small effects, typically about 0.2-0.4 standard deviation units, and account for between 3% and 10% of the variance in individual characters. All QTLs participated in epistatic interactions with other QTLs. Most of these interactions were due to additive-by-additive epistasis, which can nullify the apparent effects of single loci in our population. Adip8 interacts with all the other adiposity QTLs and seems to play a central role in the genetic system affecting obesity in this cross. Only two adiposity QTLs, Adip4 and Adip6, also affect tail length, indicating largely separate genetic control of variation in adiposity and skeletal size. Body size and obesity QTLs in the same locations as those discovered here are commonly found in mapping experiments with other mouse strains.
Cheverud
J M
JM
Department of Anatomy & Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA. cheverud@pcg.wustl.edu
Vaughn
T T
TT
Pletscher
L S
LS
Peripato
A C
AC
Adams
E S
ES
Erikson
C F
CF
King-Ellison
K J
KJ
D000273:Adipose Tissue; D000483:Alleles; D000818:Animals; D001824:Body Constitution / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D003433:Crosses, Genetic; D004843:Epistasis, Genetic; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018895:Microsatellite Repeats; D009765:Obesity / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D013623:Tail / Q000033:anatomy & histology