The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus
The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus
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DOI：
10.1007/s004390050166
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发表时间：
1996-07-01
期刊：
影响因子：
5.3
通讯作者：
Kidd, KK
中科院分区：
文献类型：
--
作者：
Chang, FM;Kidd, JR;Kidd, KK
多巴胺D4受体基因（DRD 4）在第三外显子中具有表达多态性，可能具有功能相关性。多态性存在于两个层次。在较高水平上，存在编码16个氨基酸的48个碱基对（bp）的不完全串联重复;已鉴定出具有2个（32个氨基酸）至10个（160个氨基酸）重复的等位基因。重复序列的不完美性导致了更微妙的变异水平，因为具有相同重复序列数的等位基因在精确序列或48-bp单元变体的顺序上可能不同。我们对这种表达的多态性进行了一项全球调查，作为了解多态性的进化意义和起源以及了解可能在该基因座上起作用的选择力（如果有的话）的一种方法。作为第一步，我们确定了来自36个不同群体的1,327个个体的DRD 4重复多态性的重复数基因型。等位基因频率在不同人群中差异很大。4-重复等位基因是最普遍的（全球平均等位基因频率= 64.3%），并出现在每个人群中的频率范围为0.16至0.96。7-重复等位基因是第二常见的（全球平均值= 20.6%），在美洲非常常见（平均频率= 48.3%），但在东亚和南亚仅偶尔出现（平均频率= 1.9%）。2-重复等位基因是第三常见的（全球平均频率= 8.2%），在东亚和南亚非常常见（平均频率= 18.1%），而在美洲（平均频率= 2.9%）和非洲（平均频率= 1.7%）不常见。只有三个常见的重复数等位基因（4，7和2）的多态性的普遍性表明，多态性是古老的，并出现在现代人类的全球分散之前。不同人群中这种表达多态性的实际等位基因频率的多样性强调了在设计和解释任何与这种多态性相关的研究时人群考虑的重要性。
The dopamine D4 receptor gene (DRD4) has an expressed polymorphism in the third exon that may have functional relevance. The polymorphism exists at two levels. At the higher level there is an imperfect tandem repeat of 48 base pairs (bp) coding for 16 amino acids; alleles have been identified with 2 (32 amino acids) to 10 (160 amino acids) repeats. The imperfect nature of the repeats is responsible for a more subtle level of variation since alleles with the same number of repeats can differ in the exact sequences or in the order of the variants of the 48-bp unit. We have undertaken a global survey of this expressed polymorphism as one approach to understanding the evolutionary significance and origins of the polymorphism as well as understanding what selective forces, if any, may be operating at this locus. As the first step, we have determined the repeat number genotype of the DRD4 repeat polymorphism in 1,327 individuals from 36 different populations. The allele frequencies differ considerably among the different populations. The 4-repeat allele was the most prevalent (global mean allele frequency = 64.3%) and appeared in every population with a frequency ranging from 0.16 to 0.96. The 7-repeat allele was the second most common (global mean = 20.6%), appearing quite frequently in the Americas (mean frequency = 48.3%) but only occasionally in East and South Asia (mean frequency = 1.9%). The 2-repeat allele was the third most common (global mean frequency = 8.2%) and was quite frequent in East and South Asia (mean frequency = 18.1%) while uncommon in the Americas (mean frequency = 2.9%) and Africa (mean frequency = 1.7%). The universality of the polymorphism with only three common repeat-number alleles (4, 7, and 2) indicates that the polymorphism is ancient and arose before the global dispersion of modern humans. The diversity of actual allele frequencies for this expressed polymorphism among different populations emphasizes the importance of population considerations in the design and interpretation of any association studies carried out with this polymorphism.