TY - JOUR
T1 - Single and interacting QTLs for cholesterol gallstones revealed in an intercross between mouse strains NZB and SM
AU - Lyons, Malcolm A.
AU - Korstanje, Ron
AU - Li, Renhua
AU - Sheehan, Susan M.
AU - Walsh, Kenneth A.
AU - Rollins, Jarod A.
AU - Carey, Martin C.
AU - Paigen, Beverly
AU - Churchill, Gary A.
PY - 2005/3
Y1 - 2005/3
N2 - Quantitative trait locus (QTL) mapping was employed to investigate the genetic determinants of cholesterol gallstone formation in a large intercross between mouse strains SM/J (resistant) and NZB/B1NJ (susceptible). Animals consumed a gallstonepromoting diet for 18 weeks. QTL analyses were performed using gallstone weight and gallstone absence/presence as phenotypes; various models were explored for genome scans. We detected seven single QTLs: three new, significant QTLs were named Lith17 [chromosome (Chr) 5, peak = 60 cM, LOD = 5.4], Lith18 (Chr 5, 76 cM, LOD = 4.3), and Lith19 (Chr 8, 0 cM, LOD = 5.3); two confirmed QTLs identified previously and were named Lith20 (Chr 9, 44 cM, LOD = 2.7) and Lith21 (Chr 10, 24 cM, LOD = 2.9); one new, suggestive QTL (Chr 17) remains unnamed. Upon searching for epistatic interactions that contributed to gallstone susceptibility, the final suggestive QTL on Chr 7 was determined to interact significantly with Lith18 and, therefore, was named Lith22 (65 cM). A second interaction was identified between Lith19 and a locus on Chr 11; this QTL was named Lith23 (13 cM). mRNA expression analyses and amino acid haplotype analyses likely eliminated Slc10a2 as a candidate gene for Lith19. The QTLs identified herein largely contributed to gallstone formation rather than gallstone severity. Cloning the genes underlying these murine QTLs should facilitate prediction and cloning of the orthologous human genes.
AB - Quantitative trait locus (QTL) mapping was employed to investigate the genetic determinants of cholesterol gallstone formation in a large intercross between mouse strains SM/J (resistant) and NZB/B1NJ (susceptible). Animals consumed a gallstonepromoting diet for 18 weeks. QTL analyses were performed using gallstone weight and gallstone absence/presence as phenotypes; various models were explored for genome scans. We detected seven single QTLs: three new, significant QTLs were named Lith17 [chromosome (Chr) 5, peak = 60 cM, LOD = 5.4], Lith18 (Chr 5, 76 cM, LOD = 4.3), and Lith19 (Chr 8, 0 cM, LOD = 5.3); two confirmed QTLs identified previously and were named Lith20 (Chr 9, 44 cM, LOD = 2.7) and Lith21 (Chr 10, 24 cM, LOD = 2.9); one new, suggestive QTL (Chr 17) remains unnamed. Upon searching for epistatic interactions that contributed to gallstone susceptibility, the final suggestive QTL on Chr 7 was determined to interact significantly with Lith18 and, therefore, was named Lith22 (65 cM). A second interaction was identified between Lith19 and a locus on Chr 11; this QTL was named Lith23 (13 cM). mRNA expression analyses and amino acid haplotype analyses likely eliminated Slc10a2 as a candidate gene for Lith19. The QTLs identified herein largely contributed to gallstone formation rather than gallstone severity. Cloning the genes underlying these murine QTLs should facilitate prediction and cloning of the orthologous human genes.
UR - http://www.scopus.com/inward/record.url?scp=17644375869&partnerID=8YFLogxK
U2 - 10.1007/s00335-004-2446-5
DO - 10.1007/s00335-004-2446-5
M3 - Article
C2 - 15834632
AN - SCOPUS:17644375869
SN - 0938-8990
VL - 16
SP - 152
EP - 163
JO - Mammalian Genome
JF - Mammalian Genome
IS - 3
ER -