Next-generation sequencing demands next-generation phenotyping.
Next-generation sequencing demands next-generation phenotyping.
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DOI：
10.1002/humu.22048
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发表时间：
2012-05
期刊：
影响因子：
3.9
通讯作者：
Biesecker, Leslie G.
中科院分区：
文献类型：
--
作者：
Hennekam, Raoul C. M.;Biesecker, Leslie G.
下一代测序（NGS）是自X光片以来最强大的诊断工具。NGS将有助于大规模的诊断-允许在一次检测中询问所有基因。有人认为，NGS将减少一般表型分型的需要，特别是医学遗传学家。我们认为，NGS将转移表型的焦点和方法。我们预测，用于诊断目的的NGS将产生几个基因的变异，这些变异的后果将需要分析并与临床结果相结合，以做出诊断。医学专家的诊断技能将从NGS测试前的鉴别诊断模式转变为NGS测试后的诊断评估模式。在研究中，表型分析和医学遗传评估也将是必不可少的。NGS可以识别以孟德尔模式遗传的表型中的主要致病变体，但生物学要复杂得多。表型是由几个基因的作用，以及表观遗传和环境影响引起的。剖析所有的影响，需要持续和详细的表型，临床诊断分配的细化，和NGS数据的迭代分析。我们的结论是，将有一个表型和临床分析的关键需求，医学遗传学家是唯一的定位，以满足这一需求。
Next-Generation Sequencing (NGS) is the most powerful diagnostic tool since the roentgenogram. NGS will facilitate diagnosis on a massive scale –allowing interrogation of all genes in a single assay. It has been suggested that NGS will decrease the need for phenotyping in general, and medical geneticists in particular. We argue that NGS will shift focus and approach of phenotyping. We predict that NGS performed for diagnostic purposes will yield variants in several genes, and consequences of these variants will need to be analyzed and integrated with clinical findings to make a diagnosis. Diagnostic skills of medical specialists will shift from a pre-NGS-test differential diagnostic mode to a post-NGS-test diagnostic assessment mode. In research phenotyping and medical genetic assessments will remain essential as well. NGS can identify primary causative variants in phenotypes inherited in a Mendelian pattern, but biology is much more complex. Phenotypes are caused by the actions of several genes, and epigenetic and environmental influences. Dissecting all influences necessitates ongoing and detailed phenotyping, refinement of clinical diagnostic assignments, and iterative analyses of NGS data. We conclude that there will be a critical need for phenotyping and clinical analysis and that medical geneticists are uniquely positioned to address this need.
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DOI：
10.1352/0895-8017(2005)110
发表时间：
2005-09-01
期刊：
AMERICAN JOURNAL ON MENTAL RETARDATION
影响因子：
--
作者：
Dykens, EM;Rosner, BA;Sagun, J
通讯作者：
Sagun, J
DOI：
10.1038/nrg2918
发表时间：
2011-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.8
作者：
Xu, Bin;Roos, J. Louw;Dexheimer, Phillip;Boone, Braden;Plummer, Brooks;Levy, Shawn;Gogos, Joseph A.;Karayiorgou, Maria
通讯作者：
Karayiorgou, Maria
影响因子：
2
作者：
Allanson, Judith E.;Biesecker, Leslie G.;Hennekam, Raoul C. M.
通讯作者：
Hennekam, Raoul C. M.