Cox Nancy J, Hayes M Geoffrey, Roe Cheryl A, Tsuchiya Takafumi, Bell Graeme I
Department of Human Genetics, the University of Chicago, Chicago, Illinois 60637, USA.
Diabetes. 2004 Feb;53 Suppl 1:S19-25. doi: 10.2337/diabetes.53.2007.s19.
The follow-up studies to the original report of association of variation at calpain 10 (CAPN10) with type 2 diabetes in the Mexican-American population of Starr County, Texas, encompass a broad range of science. There are association studies on genetic variation at CAPN10 in different human populations over a range of phenotypes related to type 2 diabetes, physiological studies on the biological functions of calpain proteases, and evolutionary studies on CAPN10 and the NIDDM1 region. We review here the studies published to date on CAPN10, as well as the latest findings from positional cloning studies on a number of other complex disorders. Collectively, these studies provide perspective on the challenges of moving from the linkage mapping and positional cloning studies on which we have been focused to an understanding of the biology shaping the relationship of genotype to phenotype at loci influencing susceptibility to complex disorders like type 2 diabetes.
对德克萨斯州斯塔尔县墨西哥裔美国人中钙蛋白酶10（CAPN10）变异与2型糖尿病关联的原始报告进行的后续研究，涵盖了广泛的科学领域。有关于不同人群中与2型糖尿病相关一系列表型的CAPN10基因变异的关联研究、钙蛋白酶生物学功能的生理学研究以及CAPN10和NIDDM1区域的进化研究。我们在此回顾迄今已发表的关于CAPN10的研究，以及对其他一些复杂疾病进行定位克隆研究的最新发现。总体而言，这些研究为我们从一直关注的连锁图谱和定位克隆研究转向理解影响复杂疾病（如2型糖尿病）易感性的基因座上基因型与表型关系的生物学机制所面临的挑战提供了视角。
