Department of Cardiovascular Genetics, Experimental and Clinical Research Center (ECRC), Charité-University Medicine Berlin and Max Delbrück Center (MDC) for Molecular Medicine, Lindenberger Weg 80, 13125 Berlin, Germany. Department of Biochemistry, Free University Berlin, Berlin, Germany. Tel.: +49-(0)30-450540123; Fax: +49-(0)30-84131699;
Brief Funct Genomics. 2014 Jan;13(1):51-65. doi: 10.1093/bfgp/elt040. Epub 2013 Oct 3.
Congenital heart diseases (CHD) represent the most common birth defect in human. The majority of cases are caused by a combination of complex genetic alterations and environmental influences. In the past, many disease-causing mutations have been identified; however, there is still a large proportion of cardiac malformations with unknown precise origin. High-throughput sequencing technologies established during the last years offer novel opportunities to further study the genetic background underlying the disease. In this review, we provide a roadmap for designing and analyzing high-throughput sequencing studies focused on CHD, but also with general applicability to other complex diseases. The three main next-generation sequencing (NGS) platforms including their particular advantages and disadvantages are presented. To identify potentially disease-related genomic variations and genes, different filtering steps and gene prioritization strategies are discussed. In addition, available control datasets based on NGS are summarized. Finally, we provide an overview of current studies already using NGS technologies and showing that these techniques will help to further unravel the complex genetics underlying CHD.
先天性心脏病（CHD）是人类最常见的出生缺陷。大多数病例是由复杂的遗传改变和环境影响共同引起的。过去已经确定了许多致病突变，但仍有很大一部分心脏畸形的精确起源未知。近年来建立的高通量测序技术为进一步研究疾病的遗传背景提供了新的机会。在这篇综述中，我们提供了设计和分析专注于 CHD 的高通量测序研究的路线图，但也具有普遍适用于其他复杂疾病的适用性。介绍了三种主要的下一代测序（NGS）平台，包括它们各自的优缺点。为了鉴定潜在的与疾病相关的基因组变异和基因，讨论了不同的过滤步骤和基因优先级策略。此外，还总结了基于 NGS 的现有对照数据集。最后，我们概述了已经使用 NGS 技术的当前研究，并表明这些技术将有助于进一步揭示 CHD 背后的复杂遗传机制。
