TY - JOUR
T1 - Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice
AU - Wittenburg, Henning
AU - Lammert, Frank
AU - Wang, David Q.H.
AU - Churchill, Gary A.
AU - Li, Renhua
AU - Bouchard, Guylaine
AU - Carey, Martin C.
AU - Paigen, Beverly
PY - 2002/4
Y1 - 2002/4
N2 - We employed quantitative trait locus (QTL) mapping in a backcross between gallstone-susceptible SWR/J and gallstone-resistant AKR/J inbred mice to identify additional susceptibility loci for cholesterol gallstone formation. After 12 wk of feeding the mice a lithogenic diet, we phenotyped 330 backcross progeny for gallstones, gallbladder mucin accumulation, liver weight, and body weight. Marker-based regression analysis revealed significant single QTLs associated with gallstone formation on chromosome 9 and the liver weight/body weight ratio on chromosomes 5 and X. A search for gene pairs detected significant gene-gene interactions for mucin accumulation between loci on chromosomes 5 and 11 and suggestive gene-gene interactions linked to gallstone formation between the QTL on chromosome 9 and loci on chromosomes 6 and 15. These findings uncover new QTLs for cholesterol gallstones, reveal independent loci for mucin accumulation, and demonstrate the importance of considering gene-gene interactions in cholesterol cholelithiasis. According to standard nomenclature, the gallstone QTL on chromosome 9 is named Lith5.
AB - We employed quantitative trait locus (QTL) mapping in a backcross between gallstone-susceptible SWR/J and gallstone-resistant AKR/J inbred mice to identify additional susceptibility loci for cholesterol gallstone formation. After 12 wk of feeding the mice a lithogenic diet, we phenotyped 330 backcross progeny for gallstones, gallbladder mucin accumulation, liver weight, and body weight. Marker-based regression analysis revealed significant single QTLs associated with gallstone formation on chromosome 9 and the liver weight/body weight ratio on chromosomes 5 and X. A search for gene pairs detected significant gene-gene interactions for mucin accumulation between loci on chromosomes 5 and 11 and suggestive gene-gene interactions linked to gallstone formation between the QTL on chromosome 9 and loci on chromosomes 6 and 15. These findings uncover new QTLs for cholesterol gallstones, reveal independent loci for mucin accumulation, and demonstrate the importance of considering gene-gene interactions in cholesterol cholelithiasis. According to standard nomenclature, the gallstone QTL on chromosome 9 is named Lith5.
KW - Gene-gene interaction
KW - Genetics
KW - Inbred mouse strains
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=0346109626&partnerID=8YFLogxK
U2 - 10.1152/physiolgenomics.00097.2001
DO - 10.1152/physiolgenomics.00097.2001
M3 - Article
C2 - 11842132
AN - SCOPUS:0346109626
SN - 1531-2267
VL - 2002
SP - 67
EP - 77
JO - Physiological Genomics
JF - Physiological Genomics
IS - 8
ER -