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Publication : Association of a lithogenic Abcg5/Abcg8 allele on Chromosome 17 (Lith9) with cholesterol gallstone formation in PERA/EiJ mice.

First Author  Wittenburg H Year  2005
Journal  Mamm Genome Volume  16
Issue  7 Pages  495-504
PubMed ID  16151694 Mgi Jnum  J:97424
Mgi Id  MGI:3575406 Doi  10.1007/s00335-005-0006-2
Citation  Wittenburg H, et al. (2005) Association of a Lithogenic Abcg5/Abcg8 allele on Chromosome 17 (Lith9) with Cholesterol Gallstone Formation in PERA/EiJ mice. Mamm Genome 16(7):495-504
abstractText  To examine further the genetic determinants of cholesterol gallstone susceptibility in inbred mice, we performed quantitative trait locus (QTL) analysis of an intercross of gallstone susceptible PERA/EiJ and gallstone resistant DBA/2J inbred mice. 324 F2 offspring were phenotyped for cholelithiasis during consumption of a lithogenic diet and genotyped using microsatellite markers. Linkage analysis was performed by interval mapping. In addition, we analyzed the combined datasets from this cross and an independent cross of strain PERA and gallstone resistant I/Ln mice. QTL mapping detected one significant new gallstone susceptibility (Lith) locus on chromosome 13 (Lith15). A second significant QTL on Chr 6 (Lith16) confirmed a previous QTL. Furthermore, suggestive QTLs confirmed Lith loci from previous crosses on chromosomes 1, 2, 5, 16 and X. QTL analysis of the dataset derived from the combined crosses increased the detection power and narrowed confidence intervals of Lith loci on chromosomes 2, 6, 13 and 16. Moreover, the analysis of combined datasets revealed a shared QTL between both crosses on chromosome 17 (Lith9). Significantly higher mRNA expression of Abcg5 and Abcg8 in strain PERA compared with strains I/Ln and DBA/2 further substantiated that the PERA allele of Abcg5/Abcg8 was responsible for lithogenicity underlying Lith9.
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