Stylianou Ioannis M, Langley Sarah R, Walsh Kenneth, Chen Yuan, Revenu Céline, Paigen Beverly
The Jackson Laboratory, Bar Harbor, ME, USA.
J Lipid Res. 2008 Nov;49(11):2402-13. doi: 10.1194/jlr.M800244-JLR200. Epub 2008 May 23.
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.
小鼠基因组学的最新进展揭示了常见近交系之间单核苷酸多态性（SNP）形式的显著差异。这使得表征密切相关的品系以及鉴定不同的基因成为可能；此类基因可能是数量性状的成因。小鼠品系DBA/1J和DBA/2J在SNP水平上仅相差5.6%。这些品系在许多代谢和脂质表型上存在差异，例如血浆甘油三酯（TG）和高密度脂蛋白（HDL）水平。这两个品系之间的杂交在294个后代中揭示了多个数量性状基因座（QTL）。我们在染色体（Chr）1、2、3、4、8、9、10、11、12、13、14、16和19上鉴定出显著的TG QTL，在Chr 3、9和16上鉴定出显著的HDL QTL。一些QTL定位于两个品系之间变异性有限的染色体上，从而便于鉴定候选基因。我们认为促甲状腺激素受体（Tshr）是Chr 12上TG和HDL水平的QTL基因，而印度刺猬因子（Ihh）可能是Chr 1上TG QTL的原因。这种杂交突出了杂交密切相关品系以便后续鉴定QTL基因的优势。
