Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Evid Based Complement Alternat Med. 2011;2011:215653. doi: 10.1155/2011/215653. Epub 2011 May 5.
Objective. To explore the genetic traits of Kidney-yang deficiency syndrome (KDS). Design. Twelve KDS subjects and three spouses from a typical KDS family were recruited. Their genomic DNA samples were genotyped by Affymetrix 100K single-nucleotide polymorphism (SNP) arrays. The linkage disequilibrium (LD) SNPs were generated using GeneChip DNA analysis software (GDAS, Affymetrix). Genes located within 100 bp of the flanks of LD SNPs were mined via GeneView. 29 exons of the doublecortin domain containing 5 (DCDC5), a representative gene within the flank of an LD SNP, were resequenced. Results. Five LD SNPs display midrange linkage with KDS. Two genes with established functions, DCDC5 and Leucyl-tRNA synthetase, were mined in the flanks of LD SNPs. Resequencing of DCDC5 revealed a nonsynonymous variation, in which 3764T/A was replaced by C/G. Accordingly, the Ser(1172) was substituted by Pro(1172). The S1172P substitution effect was evaluated as "possibly damaging" by PolyPhen. Conclusion. We have identified a genomic variation of DCDC5 based on the LD SNPs derived from a KDS family. DCDC5 and other genes surrounding these SNPs display some relationships with key symptoms of KDS.
目的。探索肾阳虚证（KDS）的遗传特征。
设计。从一个典型的 KDS 家系中招募了 12 名 KDS 患者和 3 名配偶。他们的基因组 DNA 样本通过 Affymetrix 100K 单核苷酸多态性（SNP）芯片进行基因分型。利用 GeneChip DNA 分析软件（GDAS，Affymetrix）生成连锁不平衡（LD）SNP。通过 GeneView 挖掘位于 LD SNP 侧翼 100bp 内的基因。对位于 LD SNP 侧翼的代表性基因双皮质素结构域包含 5 号（DCDC5）的 29 个外显子进行重测序。
结果。五个 LD SNP 与 KDS 显示中等程度的连锁。在 LD SNP 的侧翼挖掘到了两个具有明确功能的基因，DCDC5 和亮氨酰-tRNA 合成酶。DCDC5 重测序发现一个非同义变异，其中 3764T/A 被 C/G 取代。因此，丝氨酸（1172）被脯氨酸（1172）取代。PolyPhen 评估 S1172P 取代效应为“可能有害”。
结论。我们基于 KDS 家系中衍生的 LD SNP 确定了 DCDC5 的基因组变异。DCDC5 和其他围绕这些 SNP 的基因与 KDS 的关键症状有一定的关系。
