Yagil Yoram, Yagil Chana
Department of Nephrology and Hypertension, Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Ben-Gurion University, Barzilai Medical Center Campus, Ashkelon 78306, Israel.
Trends Cardiovasc Med. 2006 Feb;16(2):35-8. doi: 10.1016/j.tcm.2005.11.001.
Complex diseases are polygenic and multifactorial. The outcome of two decades of search for the culprit genes in complex diseases involving the cardiovascular system has been less than satisfactory. Genomic studies using linkage analysis have led so far to the detection of a large number of quantitative trait loci that embed a large number of candidate genes. Transcriptomic studies using differential gene expression profiling and DNA microarrays have also generated hundreds of potential candidate genes. None of these genetic strategies has enabled researchers to reduce the number of genes to a manageable number or to identify the specific culprit genes. We recently proposed that the search for genes involved in complex diseases such as hypertension might benefit from an integration of genomics and transcriptomics as a logical alternative strategy to using either approach alone. We applied this integrated genomic-transcriptomic approach to identify the genes that are involved in the pathogenesis of hypertension in the Sabra rat model of salt susceptibility. We successfully identified seven novel candidate genes for hypertension, an outcome that could not have been achieved by genomics or transcriptomics alone.
复杂疾病是多基因和多因素的。在涉及心血管系统的复杂疾病中寻找致病基因的二十年成果并不理想。使用连锁分析的基因组研究到目前为止已检测到大量包含大量候选基因的数量性状位点。使用差异基因表达谱和DNA微阵列的转录组学研究也产生了数百个潜在的候选基因。这些遗传策略都未能使研究人员将基因数量减少到可管理的数量或识别出特定的致病基因。我们最近提出，寻找诸如高血压等复杂疾病相关基因可能受益于基因组学和转录组学的整合，这是一种合理的替代策略，可替代单独使用任何一种方法。我们应用这种整合的基因组 - 转录组学方法来鉴定盐敏感性Sabra大鼠模型中高血压发病机制所涉及的基因。我们成功鉴定出七个新的高血压候选基因，这一结果单靠基因组学或转录组学是无法实现的。
