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.

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 Ser1172 was substituted by Pro1172. 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.