Identification of Linkage Disequilibrium SNPs from a Kidney-Yang Deficiency Syndrome Pedigree
Identification of Linkage Disequilibrium SNPs from a Kidney-Yang Deficiency Syndrome Pedigree
复制标题
肾阳虚证谱系连锁不平衡 SNP 的鉴定。
DOI：
10.1142/s0192415x09006953
复制
发表时间：
2009-01-01
影响因子：
5.7
通讯作者：
Wang, Mi-Qu
中科院分区：
文献类型：
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作者：
Ding, Wei Jun;Zeng, Ying Zi;Wang, Mi-Qu
为探讨肾阳虚证的遗传特征，采用肾阳虚证国家诊断标准，收集肾阳虚证患者。每个候选KDS患者来自一个典型的家庭，由5名独立的中医诊断，并重复3年，所有的12月的第一个星期六。分离15份基因组DNA，并通过Affyphase 100 K阵列进行单核苷酸多态性（SNP）基因分型。然后使用合适的工具进行连锁不平衡（LD）分析和LD SNPs的生物信息学挖掘。结果表明，我们的中医诊断程序可以有效地收集KDS的主题，从而为KDS的连锁分析提供了坚实的基础。其中5个SNP（rs 514207、rs 1054020、rs7685923、rs 10515889和rs 10516202）被鉴定为LD SNPs，代表了一组前所未有的来自中医证候的LD SNPs。这些SNP在KDS家族中表现出中等范围的连锁不平衡。在这些SNPs的100 bp内鉴定出两个具有既定功能的基因。一种是含有5的人双皮质素结构域，其选择性地与单糖、二糖或三糖碳水化合物相互作用并涉及某些信号级联。另一个是亮氨酰-tRNA合成酶，也是半胱氨酰-tRNA氨酰化和蛋白质生物合成的多效性基因。总之，KDS在基因内水平上参与了特殊的SNP连锁不平衡，这些SNP侧翼内的基因提示了KDS的一些基本症状。然而，需要有明确的证据来确认或排除这些基因座，并确定其生物活性。
In order to probe the genetic traits of Kidney-yang Deficiency Syndrome (KDS), we employed a national standard of KDS diagnosis for the collection of KDS subjects. Each candidate KDS subject from a typical family was diagnosed by 5 independent physicians of Traditional Chinese Medicine (TCM), and repeated for 3 years, all on the first Saturday of December. Fifteen samples of genomic DNA were isolated and genotyped by Affymetrix 100 K arrays of single nucleotide polymorphism (SNP). Then appropriate tools were used for the analysis of linkage disequilibrium (LD) and bioinformatic mining of LD SNPs. The results indicated that our procedure of TCM diagnosis can effectively collect KDS subjects and therefore provide substantial basis for the linkage analysis of KDS. Five SNPs (i.e. rs514207, rs1054020, rs7685923, rs10515889 and rs10516202) were identified as LD SNPs from this KDS family, representing an unprecedented set of LD SNPs derived from TCM syndrome. These SNPs demonstrate midrange linkage disequilibrium within the KDS family. Two genes with established functions were identified within 100 bp of these SNPs. One is Homo sapiens double cortin domain containing 5, which interacts selectively with mono-, di- or tri-saccharide carbohydrate and involves certain signaling cascades. Another one, leucyl-tRNA synthetase, is also a pleiotropic gene response to cysteinyl-tRNA aminoacylation and protein biosynthesis. In conclusion, KDS is involved in special SNP linkage disequilibrium in the intragenic level, and genes within the flanks of these SNPs suggest some essential symptoms of KDS. However, definitive evidence to confirm or exclude these loci and to establish their biological activities will be required.