Enhanced Data from Orofacial Cleft Trios to Strengthen the Gabriella Miller Kids First (GMKF) Discovery Goals

摘要 唇（CL）、腭（CP）或两者（CLP）的非综合征性口面裂（OFC）发生在约1/700的活产婴儿中 在世界范围内，这是一个非常严重的问题，因此构成了人类结构性出生缺陷的很大一部分。OFC需要外科手术， 营养、牙科、言语、医疗和行为干预，对公共卫生、经济、 个人负担。平均而言，患有OFC的儿童最初面临喂养困难，然后经历 密集的医疗，牙科和语言干预，导致估计的终身治疗总成本为 大约二十万美元此外，出生时患有眶额皮层的人婴儿死亡率更高， 其他生命阶段，以及其他疾病（特别是包括一些癌症）的风险更高。 OFC的病因是复杂的，显然包括一个主要的遗传成分，约50 迄今为止发现的显著相关的基因座。因此，我们和其他人得到了各种NIH的支持， 用于SNP阵列基因分型的程序，以及，值得注意的是，用于主要来自 盖比瑞拉米勒儿童优先计划（GMKF）到目前为止，我们已经通过五个单独的GMKF接收了WGS 共为1，486名OFC先证者提供赠款。来自这些项目的序列数据通过 GMKF数据资源中心和表型数据通过GMKF数据资源中心和（在xome cases）dbGaP.到目前为止，最关键的表型数据已经上传到dbGaP（例如性别， 人群/种族，OFC类型），但这些研究中还有大量其他表型数据可用 (e.g.关于OFC出生缺陷、妊娠史、医疗/手术史等的详细信息），这些信息尚未纳入 这些项目的可用数据。这个项目的目标是使更多的语义策划的数据 通过GMKF向研究界提供OFC研究的内容，以扩大 从GMKF口面裂三重奏的数据的范围和价值，并促进跨GMKF研究 分析。

ABSTRACT Nonsyndromic orofacial clefts (OFCs) of the lip (CL), palate (CP), or both (CLP) occur in about 1/700 live births worldwide, and thus comprise a significant proportion of human structural birth defects. OFCs require surgical, nutritional, dental, speech, medical, and behavioral interventions, imposing substantial public health, economic, and personal burdens. On average a child with an OFC initially faces feeding difficulties, then undergoes intensive medical, dental, and speech interventions, leading to an estimated total lifetime treatment cost of about $200,000. Further, individuals born with an OFC have higher infant mortality, higher mortality rates at all other stages of life, and higher risk for other disorders (notably including some cancers). The etiology of OFCs is complex, clearly including a major genetic component with approximately 50 significantly associated loci identified to date. Thus we and others have received support from various NIH programs for SNP array genotyping, and also, notably, for whole-genome sequencing (WGS) primarily from the Gabriella Miller Kids First Initiative (GMKF). To date, we have received WGS through five separate GMKF grants for a total of 1,486 OFC proband trios. The sequence data from these projects are shared through the GMKF Data Resource Center and the phenotype data through the GMKF Data Resource Center and (in xome cases) dbGaP. To date, the most critical phenotype data has been uploaded to dbGaP (e.g. sex, population/ethnicity, OFC type), but there is a wealth of other phenotypic data available from these studies (e.g. details on the OFC birth defect, pregnancy history, medical/surgical history, etc) that is not yet part of the available data for these projects. The goal of this project is to make additional semantically curated data elements from the OFC studies available to the research community through GMKF, in order to expand the scope and value of the data from the GMKF orofacial cleft trios and to facilitate cross GMKF-study analyses.