Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice

Henning Wittenburg; Frank Lammert; David Q.H. Wang; Gary A. Churchill; Renhua Li; Guylaine Bouchard; Martin C. Carey; Beverly Paigen

doi:10.1152/physiolgenomics.00097.2001

Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice

Henning Wittenburg, Frank Lammert, David Q.H. Wang, Gary A. Churchill, Renhua Li, Guylaine Bouchard, Martin C. Carey, Beverly Paigen^*

^*Corresponding author for this work

Surgery

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Abstract

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.

Original language	English
Pages (from-to)	67-77
Number of pages	11
Journal	Physiological Genomics
Volume	2002
Issue number	8
DOIs	https://doi.org/10.1152/physiolgenomics.00097.2001
State	Published - Apr 2002

Keywords

Gene-gene interaction
Genetics
Inbred mouse strains
Obesity

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10.1152/physiolgenomics.00097.2001

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title = "Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice",

abstract = "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.",

keywords = "Gene-gene interaction, Genetics, Inbred mouse strains, Obesity",

author = "Henning Wittenburg and Frank Lammert and Wang, {David Q.H.} and Churchill, {Gary A.} and Renhua Li and Guylaine Bouchard and Carey, {Martin C.} and Beverly Paigen",

year = "2002",

month = apr,

doi = "10.1152/physiolgenomics.00097.2001",

language = "English",

volume = "2002",

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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

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JO - Physiological Genomics

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ER -

Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice

Abstract

Keywords

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