Hill Annie E, Lander Eric S, Nadeau Joseph H
Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Methods Mol Med. 2006;128:153-72. doi: 10.1385/1-59745-159-2:153.
Many biological traits and heritable diseases are multifactorial, involving combinations of genetic variants and environmental factors. To dissect the genetic basis for these traits and to characterize their functional consequences, mouse models are widely used, not only because of their genetic and physiological similarity to humans, but also because an extraordinary variety of genetic resources enable rigorous functional studies. Chromosome substitution strains (CSSs) are a powerful complement to existing resources for studying multigenic traits. By partitioning the genome into a panel of new inbred strains with single chromosome substitutions, one strain for each of the autosomes, the X and Y chromosome, and the mitochondria, unique experimental designs and considerable statistical power are possible. Multigenic trait genes (or quantitative trait loci [QTLs]) with weak effects are easily detected, linkage and congenic crosses can be quickly made, gene interactions are readily characterized, and discovery of QTLs is greatly accelerated. Several published studies demonstrate the considerable utility of these strains and new applications for CSSs continue to be discovered.
许多生物学性状和遗传性疾病是多因素的，涉及遗传变异和环境因素的组合。为了剖析这些性状的遗传基础并描述其功能后果，小鼠模型被广泛使用，这不仅是因为它们在遗传和生理上与人类相似，还因为种类繁多的遗传资源能够进行严格的功能研究。染色体代换系（CSSs）是研究多基因性状的现有资源的有力补充。通过将基因组划分为一组新的近交系，每个常染色体、X和Y染色体以及线粒体各有一个单染色体代换系，独特的实验设计和强大的统计能力成为可能。具有微弱效应的多基因性状基因（或数量性状位点[QTLs]）很容易被检测到，连锁和回交可以快速进行，基因相互作用很容易被表征，并且QTLs的发现也大大加快。一些已发表的研究证明了这些品系的巨大效用，并且CSSs的新应用仍在不断被发现。
