Castiglione C M, Deinard A S, Speed W C, Sirugo G, Rosenbaum H C, Zhang Y, Grandy D K, Grigorenko E L, Bonne-Tamir B, Pakstis A J
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
Am J Hum Genet. 1995 Dec;57(6):1445-56.
We present here the first evolutionary perspective on haplotypes at DRD2, the locus for the dopamine D2 receptor. The dopamine D2 receptor plays a critical role in the functioning of many neural circuits in the human brain. If functionally relevant variation at the DRD2 locus exists, understanding the evolution of haplotypes on the basis of polymorphic sites encompassing the gene should provide a powerful framework for identifying that variation. Three DRD2 polymorphisms (TaqI "A" and "B" RFLPs and the (CA)n short tandem repeat polymorphic in all the populations studied, and they display strong and significant linkage disequilibria with each other. The common haplotypes for the two TaqI RFLPs are separately derived from the ancestral haplotype but predate the spread of modern humans around the world. The knowledge of how the various haplotypes have evolved, the allele frequencies of the haplotypes in human populations, and the physical relationships of the polymorphisms to each other and to the functional parts of the gene should now allow proper design and interpretation of association studies.
我们在此展示了对多巴胺D2受体基因座（DRD2）单倍型的首个进化视角。多巴胺D2受体在人类大脑许多神经回路的功能中起着关键作用。如果DRD2基因座存在功能相关变异，基于包含该基因的多态性位点来理解单倍型的进化，应为识别该变异提供一个强大的框架。在所研究的所有群体中，三种DRD2多态性（TaqI“A”和“B”限制性片段长度多态性以及（CA）n短串联重复多态性）均存在，并且它们彼此之间呈现出强烈且显著的连锁不平衡。两种TaqI限制性片段长度多态性的常见单倍型分别源自祖先单倍型，但早于现代人类在全球的扩散。关于各种单倍型如何进化、单倍型在人类群体中的等位基因频率，以及多态性彼此之间以及与基因功能部分的物理关系的知识，现在应该能够为关联研究进行恰当的设计和解读。
