Experiment
Linkage analysis was performed on 330 male animals from a (129S1/SvImJ x RIIIS/J)F2 intercross to identify QTLs associated with serum cholesterol levels. Animals were placed on an atherogenic diet for 8 weeks. Parental strain 129S1/SvImJ exhibits increased serum cholesterol concentrations for each lipoprotein class compared to parental strain RIIIS/J.
Significant linkage to total cholesterol mapped to 88 cM on mouse Chromosome 1 (Chol10, LOD=3.9 at D1Mit507) and 14 cM on mouse Chromosome 9 (Chol11, LOD=4.4 at D11Mit149 **note**D11Mit149 is the marker stated by the authors in association with Chol11 on chromosome 9). The QTL range of Chol10 spans 70 cM - 105 cM on chromosome 1 and the QTL range of Chol11 spans 0 cM - 30 cM on chromosome 11. 129S1/SvImJ-derived alleles confer additively inherited increased total cholesterol at both Chol10 and Chol11. Previously identified QTLs Ath1, Chab6, Hdlq5, Hdlq6, and Pcho1 colocalize within the 95% confidence interval of Chol10. (Authors theorize that Hdlq5 and Chol10 may be an identical locus.) A strong candidate gene for Chol10 is Apoa2. Apoa2 exhibits 3.6-fold greater expression in strain 129S1/SvImJ compared to RIII/J. Hdlq17 colocalizes with Chol11 and may be an identical locus.
Suggestive linkage to total cholesterol mapped to 46 cM on mouse Chromosome 12 (LOD=2.4 at D12Mit7) and 58 cM on mouse Chromosome 17 (LOD=2.4 at D17Mit221). The 95% confidence interval of the D12Mit7 locus spans 40 cM - 50 cM with 129S1/SvImJ-derived alleles conferring recessively inherited increase in total cholesterol. The 95% confidence interval of the D17Mit221 locus spans 45 cM - 60 cM with RIIIS/J-derived alleles conferring dominantly inherited increase in total cholesterol. These loci await confirmation and remain unnamed.
Significant linkages to HDL cholesterol mapped to 88 cM on mouse Chromosome 1 (Hdlq5, LOD=4.8 at D1Mit507), 14 cM on mouse Chromosome 9 (Hdlq17, LOD=9.4 at D11Mit149), and to 20 cM on mouse Chromosome 12 (Hdlq18, LOD=5.0 at D12Mit60). 129S1/SvImJ-derived alleles confer additively inherited increase in HDL cholesterol at all 3 loci. The QTL range of Hdlq5 spans 72 cM - 105 cM on chromosome 1. Previously identified QTLs Ath1, Chab6, Hdlq6, and Pcho1 colocalize within the 95% confidence interval of Hdlq5. Apoa2 is a candidate gene for Hdlq5. The QTL range of Hdlq17 spans 10 cM - 25 cM on chromosome 11. The QTL range of Hdlq18 spans 0 cM - 50 cM on chromosome 12.
12.10.2014 Curator's Note: Because Hdlq5, Hdlq17 and Hdlq18 were all previoulsy mapped using crosses that differ from the cross used here, we consider this a separate map study and the QTL mapped here to be novel; we have named them Hdlq99, Hdlq89 and Hdlq90 respectively.
Hdlq5 was originally mapped in J:84430 in 2003 using (C57BL/6J x NZB/BlNJ)F1 x C57BL/6J backcross. Hdlq17 and Hdlq18 were originally mapped in J:88486 in 2004 using an (C57BL/6J x 129S1/SvImJ)F2 intercross.
A novel QTL for non-HDL cholesterol, Nhdlq3, mapped to 58 cM on mouse Chromosome 17 (LOD=3.4 at D17Mit221). The QTL range ofNhdlq3 spans 45 cM - 60 cM with RIIIS/J-derived alleles conferring dominantly inherited increase in non-HDL cholesterol. This locus colocalizes with the suggestive locus for total cholesterol level at D17Mit221 and may representthe same QTL. Abcg5 and Abcg8are potential candidate genes for Nhdlq3 but mRNA expression of these two genes were not significantly different between parental strain 129S1/SvImJ and RIII/J.
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