Single and interacting QTLs for cholesterol gallstones revealed in an intercross between mouse strains NZB and SM

Single and interacting QTLs for cholesterol gallstones revealed in an intercross between mouse... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Single and interacting QTLs for cholesterol gallstones revealed in an intercross between mouse strains NZB and SM

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Publisher
Springer-Verlag
Copyright
Copyright © 2005 by Springer Science+Business Media, Inc.
Subject
Life Sciences; Anatomy; Cell Biology; Zoology
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-004-2446-5
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Mammalian GenomeSpringer Journals

Published: Jan 1, 2004

References

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