Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Mamm Genome. 2012 Oct;23(9-10):680-92. doi: 10.1007/s00335-012-9411-5. Epub 2012 Aug 15.
We have developed an association-based approach using classical inbred strains of mice in which we correct for population structure, which is very extensive in mice, using an efficient mixed-model algorithm. Our approach includes inbred parental strains as well as recombinant inbred strains in order to capture loci with effect sizes typical of complex traits in mice (in the range of 5% of total trait variance). Over the last few years, we have typed the hybrid mouse diversity panel (HMDP) strains for a variety of clinical traits as well as intermediate phenotypes and have shown that the HMDP has sufficient power to map genes for highly complex traits with resolution that is in most cases less than a megabase. In this essay, we review our experience with the HMDP, describe various ongoing projects, and discuss how the HMDP may fit into the larger picture of common diseases and different approaches.
我们开发了一种基于关联的方法，使用经典近交系小鼠，利用高效的混合模型算法纠正种群结构，这种方法在小鼠中非常广泛。我们的方法包括近交亲本品系和重组近交系，以捕获具有典型小鼠复杂性状效应大小的基因座（在总性状变异的 5%范围内）。在过去的几年中，我们已经对杂交小鼠多样性面板（HMDP）进行了各种临床性状以及中间表型的基因分型，并表明 HMDP 具有足够的能力来绘制分辨率大多数情况下小于 1Mb 的高度复杂性状的基因图谱。在这篇文章中，我们回顾了我们在 HMDP 方面的经验，描述了各种正在进行的项目，并讨论了 HMDP 如何适应常见疾病和不同方法的更大图景。
