Application of Whole Genome Sequencing Technology in the Investigation of Genetic Causes of Fetal, Perinatal, and Early Infant Death
Application of Whole Genome Sequencing Technology in the Investigation of Genetic Causes of Fetal, Perinatal, and Early Infant Death
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DOI：
10.1177/1093526617715528
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发表时间：
2018-01-01
影响因子：
1.9
通讯作者：
Venter, Deon J.
中科院分区：
文献类型：
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作者：
Armes, Jane E.;Williams, Mark;Venter, Deon J.
胎儿、围产期和早期婴儿年龄组的死亡有多种原因，其中一部分被认为是遗传性的。在这个年轻的年龄，定义导致死亡的特定遗传畸变是有问题的，这是由于不发达表型中固有的有限表型-基因型相关性，死亡后无法评估某些表型性状，以及处理罕见疾病的问题。在这项研究中，我们的目的是提高产量的识别一个明确的遗传原因的过早死亡。因此，我们采用全基因组测序和生物信息学过滤技术对16例胎儿、围产期和早期婴儿死亡进行了全面、公正的遗传调查，这些死亡病例都进行了全面尸检。在2例病例中确定了可能的遗传原因（基因：COL 2A 1和RYR 1），在另外6例病例中确定了推测性遗传原因（基因：ARHGAP 35、BBS 7、CASZ 1、CRIM 1、DHCR 7、HADHB、HAPLN 3、HSPG 2、MYO 18 B和SRGAP 2）。这项研究表明，全基因组测序是一种重要的技术，可以确定早期死亡的遗传原因。
Death in the fetal, perinatal, and early infant age-group has a multitude of causes, a proportion of which is presumed to be genetic. Defining a specific genetic aberration leading to the death is problematic at this young age, due to limited phenotype-genotype correlation inherent in the underdeveloped phenotype, the inability to assess certain phenotypic traits after death, and the problems of dealing with rare disorders. In this study, our aim was to increase the yield of identification of a defined genetic cause of an early death. Therefore, we employed whole genome sequencing and bioinformatic filtering techniques as a comprehensive, unbiased genetic investigation into 16 fetal, perinatal, and early infant deaths, which had undergone a full autopsy. A likely genetic cause was identified in two cases (in genes; COL2A1 and RYR1) and a speculative genetic cause in a further six cases (in genes: ARHGAP35, BBS7, CASZ1, CRIM1, DHCR7, HADHB, HAPLN3, HSPG2, MYO18B, and SRGAP2). This investigation indicates that whole genome sequencing is a significantly enabling technology when determining genetic causes of early death.