Abstract
Recent advances in mouse genomics have revealed considerable variation in the form of single-nucleotide polymorphisms (SNPs) among common inbred strains. This has made it possible to characterize closely related strains and to identify genes that differ; such genes may be causal for quantitative phenotypes. The mouse strains DBA/1J and DBA/2J differ by just 5.6% at the SNP level. These strains exhibit differences in a number of metabolic and lipid phenotypes, such as plasma levels of triglycerides (TGs) and HDL. A cross between these strains revealed multiple quantitative trait loci (QTLs) in 294 progeny. We identified significant TG QTLs on chromosomes (Chrs) 1, 2, 3, 4, 8, 9, 10, 11, 12, 13, 14, 16, and 19, and significant HDL QTLs on Chrs 3, 9, and 16. Some QTLs mapped to chromosomes with limited variability between the two strains, thus facilitating the identification of candidate genes. We suggest that Tshr is the QTL gene for Chr 12 TG and HDL levels and that Ihh may account for the TG QTL on Chr 1. This cross highlights the advantage of crossing closely related strains for subsequent identification of QTL genes.
Highlights
Recent advances in mouse genomics have revealed considerable variation in the form of single-nucleotide polymorphisms (SNPs) among common inbred strains
quantitative trait locus (QTL) analysis was performed for each lipid trait at 8 weeks of age on a chow diet, at 11 weeks of age, after the mice had been on a HF diet for 3 weeks, and at 16 weeks of age, after the mice had been on the high fat diet for 8 weeks
Many of the QTLs observed for TG were either sex specific or were strongly affected by sex, as shown by a change in logarithm of the odds ratio (LOD) score .2 when comparing the genome scans using sex as additive or interactive covariate; in all such cases, males had the higher TG
Summary
Recent advances in mouse genomics have revealed considerable variation in the form of single-nucleotide polymorphisms (SNPs) among common inbred strains. This has made it possible to characterize closely related strains and to identify genes that differ; such genes may be causal for quantitative phenotypes. The mouse strains DBA/1J and DBA/2J differ by just 5.6% at the SNP level These strains exhibit differences in a number of metabolic and lipid phenotypes, such as plasma levels of triglycerides (TGs) and HDL. In this study we used two mouse strains that differ in phenotype but are genetically closely related, demonstrating that QTL genes can be identified by using models of limited genetic variability. We report the QTL found in a D1 3 D2 cross for TG, HDL, and body weight and propose some candidate genes
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