Copy Number Changes Identified Using Whole Exome Sequencing in Nonsyndromic Cleft Lip and Palate in a Honduran Population.
Copy Number Changes Identified Using Whole Exome Sequencing in Nonsyndromic Cleft Lip and Palate in a Honduran Population.
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使用全外显子组测序在洪都拉斯人群中非综合征性唇裂和腭裂中鉴定出拷贝数变化。
DOI：
10.1002/bdr2.1063
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发表时间：
2017
影响因子：
2.1
通讯作者：
HaddadJr,Joseph
中科院分区：
文献类型：
--
作者：
Cai,Yi;Patterson,KarynneE;Reinier,Frederic;Keesecker,SarahE;Blue,Elizabeth;Bamshad,Michael;HaddadJr,Joseph
背景：大多数唇裂伴或不伴腭裂的病例表现为孤立的非综合征性实体（NSCLP）。随着下一代测序技术的出现，全外显子组测序（WES）已被用于鉴定导致或增加NSCLP风险的单核苷酸变异和插入/缺失。然而，据我们所知，目前还没有发表的研究使用WES在NSCLP中研究拷贝数变化（CNCs），这是人类遗传变异的主要组成部分。本研究旨在利用WES在洪都拉斯人群中确定与NSCLP相关的CNCs。方法对27个多民族宏都拉斯家庭的2 ~ 4名成员进行swes检查。采用CoNIFER和XHMM两种算法识别cnc。优先考虑在一个以上患者中发现的CNCs，并且在参考数据集中变异频率小于5%。结果swes完成度定义为>8倍覆盖时达到WES目标的>90%,>20倍覆盖时达到WES目标的>80%。24个符合我们纳入标准的cnc被CoNIFER和XHMM识别出来。这些CNCs通过定量PCR证实。系谱分析得到3个与adh7、AHR和cryz2相对应的cnc，与NSCLP分离。三个CNCs中的两个涉及基因AHRandADH7，其已知的生物学功能可能在NSCLP中发挥作用。结论wes可用于检测可能参与NSCLP病理生理的候选CNCs。出生缺陷研究109:1257-1267,2017。©2017 Wiley期刊公司
BackgroundThe majority of cleft lip with or without cleft palate cases appear as an isolated, nonsyndromic entity (NSCLP). With the advent of next generation sequencing, whole exome sequencing (WES) has been used to identify single nucleotide variants and insertion/deletions which cause or increase the risk of NSCLP. However, to our knowledge, there are no published studies using WES in NSCLP to investigate copy number changes (CNCs), which are a major component of human genetic variation. Our study aimed to identify CNCs associated with NSCLP in a Honduran population using WES.MethodsWES was performed on two to four members of 27 multiplex Honduran families. CNCs were identified using two algorithms, CoNIFER and XHMM. Priority was given to CNCs that were identified in more than one patient and had variant frequencies of less than 5% in reference data sets.ResultsWES completion was defined as >90% of the WES target at >8 × coverage and >80% of the WES target at >20 × coverage. Twenty‐four CNCs that met our inclusion criteria were identified by both CoNIFER and XHMM. These CNCs were confirmed using quantitative PCR. Pedigree analysis produced three CNCs corresponding toADH7, AHR, andCRYZsegregating with NSCLP. Two of the three CNCs implicate genes,AHRandADH7, whose known biological functions could plausibly play a role in NSCLP.ConclusionWES can be used to detect candidate CNCs that may be involved in the pathophysiology of NSCLP. Birth Defects Research 109:1257–1267, 2017. © 2017 Wiley Periodicals, Inc.