Development of next generation sequencing panel for UMOD and association with kidney disease.
Development of next generation sequencing panel for UMOD and association with kidney disease.
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DOI：
10.1371/journal.pone.0178321
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
McKnight AJ
中科院分区：
文献类型：
--
作者：
Bailie C;Kilner J;Maxwell AP;McKnight AJ
慢性肾脏病（CKD）在成人人群中的患病率约为10%。CKD可进展为终末期肾病（ESRD），除非提供某种形式的肾脏替代治疗（慢性透析或肾移植），否则这通常是致命的。CKD具有遗传易感性，现已确定了几种遗传风险标记。UMOD基因与不同病因的CKD相关。开发了AmpliSeq下一代测序板，以促进UMOD基因的全面测序，涵盖外显子和调控区。在两项研究中评估了包含UMOD的基因组区域中的SNP和CpG位点与CKD的相关性; UK Wellcome Trust病例对照3肾移植功能障碍研究（n = 1088）和UK-ROI GENIE GWAS（n = 1726）。两台Ion Torrent机器的技术比较显示S5 XL™和PGM™机器之间100%的等位基因调用一致性。一个SNP（rs 183962941），位于UMOD的非编码区，名义上与ESRD相关（p = 0.008）。UMOD变异与估计的肾小球滤过率之间没有关联。对超过480，000个CpG位点甲基化数据的分析揭示了UMOD中的差异甲基化模式，其中最显著的是cg 03140788 p = 3.7 x 10−10。
Chronic kidney disease (CKD) has a prevalence of approximately 10% in adult populations. CKD can progress to end-stage renal disease (ESRD) and this is usually fatal unless some form of renal replacement therapy (chronic dialysis or renal transplantation) is provided. There is an inherited predisposition to CKD with several genetic risk markers now identified. The UMOD gene has been associated with CKD of varying aetiologies. An AmpliSeq next generation sequencing panel was developed to facilitate comprehensive sequencing of the UMOD gene, covering exonic and regulatory regions. SNPs and CpG sites in the genomic region encompassing UMOD were evaluated for association with CKD in two studies; the UK Wellcome Trust Case-Control 3 Renal Transplant Dysfunction Study (n = 1088) and UK-ROI GENIE GWAS (n = 1726). A technological comparison of two Ion Torrent machines revealed 100% allele call concordance between S5 XL™ and PGM™ machines. One SNP (rs183962941), located in a non-coding region of UMOD, was nominally associated with ESRD (p = 0.008). No association was identified between UMOD variants and estimated glomerular filtration rate. Analysis of methylation data for over 480,000 CpG sites revealed differential methylation patterns within UMOD, the most significant of these was cg03140788 p = 3.7 x 10−10.