Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Genet Mol Biol. 2012 Dec;35(4 (suppl)):912-8. doi: 10.1590/s1415-47572012000600004. Epub 2012 Dec 18.
Genetic studies have long suggested the important role of the DRD2 gene in psychiatric disorders and behavior. Further research has shown a conjoined effect of genes in the Chr11q22-23 region, which includes the NCAM1, TTC12, ANKK1 and DRD2 genes, or NTAD cluster. Despite a growing need to unravel the role of this cluster, few studies have taken into account interspecies and evolutionary approaches. This study shows that behaviorally relevant SNPs from the NTAD cluster, such as rs1800497 (Taq1A) and rs6277, are ancient polymorphisms that date back to the common ancestor between modern humans and Neanderthals/Denisovans. Conserved synteny and neighborhood indicate the NTAD cluster seems to have been established at least 400 million years ago, when the first Sarcopterygians emerged. The NTAD genes are apparently co-regulated and this could be attributed to adaptive functional properties, including those that emerged when the central nervous system became more complex. Finally, our findings indicate that NTAD genes, which are related to neurogenesis and dopaminergic neurotransmission, should be approached as a unit in behavioral and psychiatric genetic studies.
遗传研究长期以来表明 DRD2 基因在精神疾病和行为中的重要作用。进一步的研究表明，Chr11q22-23 区域中的基因存在联合效应，该区域包括 NCAM1、TTC12、ANKK1 和 DRD2 基因，或称为 NTAD 簇。尽管越来越需要揭示这个簇的作用，但很少有研究考虑到种间和进化方法。本研究表明，来自 NTAD 簇的与行为相关的 SNP，如 rs1800497（Taq1A）和 rs6277，是古老的多态性，可追溯到现代人类与尼安德特人/丹尼索瓦人之间的共同祖先。保守的同线性和邻近性表明，NTAD 簇似乎至少在 4 亿年前，当第一个肉鳍鱼类出现时就已经建立。NTAD 基因显然是共同调控的，这可以归因于适应性功能特性，包括当中枢神经系统变得更加复杂时出现的特性。最后，我们的发现表明，与神经发生和多巴胺能神经传递有关的 NTAD 基因应在行为和精神遗传研究中作为一个整体来研究。
