QTL
Genetic Location*
Genome Location (GRCm39)
Reference
QTL Note
Hdl4
Chr17, syntenic
J:99477
Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.
Potential candidate genes for Hdl4 (32.3 cM) on mouse Chromosome 17 as identified by ExQuest are Gnmt, Lrg1, and Sepx1 (10 cM). For QTL Insq5 (56.7 cM), potential candidate gene Abcg5 (54.5 cM) was identified. For QTL Obq4 (4 cM) and Wta4 (17 cM), potential candidate genes Plg (7.3 cM), Acat2 (7.55 cM), Acat3 (7.55 cM), Hagh (11 cM), Igfals, Decr2, Clps (17.1 cM), Tff1 (17 cM), Tff2 (17 cM), Tff3 (17 cM), and Apom were identified. Tff3 exhibits almost undetectable levels of transcription in the liver of Tally Ho animals compared C57BL/6J.
Insq5
Chr17, syntenic
J:99477
Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.
Potential candidate genes for Hdl4 (32.3 cM) on mouse Chromosome 17 as identified by ExQuest are Gnmt, Lrg1, and Sepx1 (10 cM). For QTL Insq5 (56.7 cM), potential candidate gene Abcg5 (54.5 cM) was identified. For QTL Obq4 (4 cM) and Wta4 (17 cM), potential candidate genes Plg (7.3 cM), Acat2 (7.55 cM), Acat3 (7.55 cM), Hagh (11 cM), Igfals, Decr2, Clps (17.1 cM), Tff1 (17 cM), Tff2 (17 cM), Tff3 (17 cM), and Apom were identified. Tff3 exhibits almost undetectable levels of transcription in the liver of Tally Ho animals compared C57BL/6J.
Kcal2
Chr17, syntenic
Chr17:26401012-52911704
J:117468
Previously identified QTLs Mnic1 (macronutrient intake, carbohydrate 1) and Kcal2 (kilocalorie 2) at 20 cM on mouse Chromosome 17 were confirmed by analysis of speed congenic lines. B6.CAST- (D17Mit19-D17Mit91) carries a 38 cM region of CAST/EiJ-derived DNA from D17Mit19 (3 cM; 4.7 Mb) to D17Mit91 (37.8 cM; 63.5 Mb) on a C57BL/6J genetic background. The congenic interval contains Mnic1 and Kcal2. Donor strain CAST/EiJ displays significantly higher total daily caloric intake compared to background strain C57BL/6J. Likewise, congenic line B6.CAST-(D17Mit19-D17Mit91) displays 17% higher total calorie intake compared to C57BL/6J and prefers a carbohydrate diet (27% increase) over a fat diet.
Glp1r at 18 cM is a positional candidate gene for Kcal2. Glp1r exhibits decreased expression in the hypothalamus and antral stomach, and increased expression in the pancreas, of CAST/EiJ mice compared to C57BL/6J mice. In B6.CAST- (D17Mit19-D17Mit91) mice, Glp1r expression is increased in the pancreas and decreased in the stomach compared to C57BL/6J mice. Sequence analysis of Glp1r revealed 3 polymorphisms between CAST/EiJ and C57BL/6J, one of which results in an amino acid substitution in exon 13 (C416Y). Glo1 at 16 cM is a positional candidate gene for Mnic1. Glo1 exhibits increased expression in liver and hypothalamus of congenic mice compared to C57BL/6J. Sequence analysis of Glo1 detected one silent polymorphism between CAST/EiJ and C57BL/6J. Other potential candidate genes mapping to the congenic interval include Clps (13.1 cM), Ppard (13.5 cM), and Apom.
Mnic1
Chr17, syntenic
Chr17:4854752-45670266
J:117468
Previously identified QTLs Mnic1 (macronutrient intake, carbohydrate 1) and Kcal2 (kilocalorie 2) at 20 cM on mouse Chromosome 17 were confirmed by analysis of speed congenic lines. B6.CAST- (D17Mit19-D17Mit91) carries a 38 cM region of CAST/EiJ-derived DNA from D17Mit19 (3 cM; 4.7 Mb) to D17Mit91 (37.8 cM; 63.5 Mb) on a C57BL/6J genetic background. The congenic interval contains Mnic1 and Kcal2. Donor strain CAST/EiJ displays significantly higher total daily caloric intake compared to background strain C57BL/6J. Likewise, congenic line B6.CAST-(D17Mit19-D17Mit91) displays 17% higher total calorie intake compared to C57BL/6J and prefers a carbohydrate diet (27% increase) over a fat diet.
Glp1r at 18 cM is a positional candidate gene for Kcal2. Glp1r exhibits decreased expression in the hypothalamus and antral stomach, and increased expression in the pancreas, of CAST/EiJ mice compared to C57BL/6J mice. In B6.CAST- (D17Mit19-D17Mit91) mice, Glp1r expression is increased in the pancreas and decreased in the stomach compared to C57BL/6J mice. Sequence analysis of Glp1r revealed 3 polymorphisms between CAST/EiJ and C57BL/6J, one of which results in an amino acid substitution in exon 13 (C416Y). Glo1 at 16 cM is a positional candidate gene for Mnic1. Glo1 exhibits increased expression in liver and hypothalamus of congenic mice compared to C57BL/6J. Sequence analysis of Glo1 detected one silent polymorphism between CAST/EiJ and C57BL/6J. Other potential candidate genes mapping to the congenic interval include Clps (13.1 cM), Ppard (13.5 cM), and Apom.
Obq4
Chr17, 4.92 cM
J:99477
Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.
Potential candidate genes for Hdl4 (32.3 cM) on mouse Chromosome 17 as identified by ExQuest are Gnmt, Lrg1, and Sepx1 (10 cM). For QTL Insq5 (56.7 cM), potential candidate gene Abcg5 (54.5 cM) was identified. For QTL Obq4 (4 cM) and Wta4 (17 cM), potential candidate genes Plg (7.3 cM), Acat2 (7.55 cM), Acat3 (7.55 cM), Hagh (11 cM), Igfals, Decr2, Clps (17.1 cM), Tff1 (17 cM), Tff2 (17 cM), Tff3 (17 cM), and Apom were identified. Tff3 exhibits almost undetectable levels of transcription in the liver of Tally Ho animals compared C57BL/6J.
Wta4
Chr17, 17.98 cM
Chr17:33819721-33819843
J:99477
Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.
Potential candidate genes for Hdl4 (32.3 cM) on mouse Chromosome 17 as identified by ExQuest are Gnmt, Lrg1, and Sepx1 (10 cM). For QTL Insq5 (56.7 cM), potential candidate gene Abcg5 (54.5 cM) was identified. For QTL Obq4 (4 cM) and Wta4 (17 cM), potential candidate genes Plg (7.3 cM), Acat2 (7.55 cM), Acat3 (7.55 cM), Hagh (11 cM), Igfals, Decr2, Clps (17.1 cM), Tff1 (17 cM), Tff2 (17 cM), Tff3 (17 cM), and Apom were identified. Tff3 exhibits almost undetectable levels of transcription in the liver of Tally Ho animals compared C57BL/6J.
*cM position of peak correlated region/marker