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

摘要 非综合征性唇裂(CL)、唇腭裂(CP)或两者兼而有之(CLP)发生在约1/700活产儿中 在全世界范围内，并因此构成了相当大比例的人类结构性出生缺陷。离岸金融中心需要手术， 营养、牙科、语言、医疗和行为干预，实施实质性的公共卫生、经济、 和个人负担。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，导致估计终身治疗总成本为 大约20万美元。此外，出生时患有OFC的人有更高的婴儿死亡率，更高的死亡率 生命的其他阶段，以及患其他疾病(特别是包括一些癌症)的风险更高。 OFCS的病因很复杂，显然包括一个主要的遗传成分，大约有50 到目前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 SNP阵列基因分型程序，还有值得注意的是，主要来自 加布里埃拉·米勒儿童优先倡议(GMKF)到目前为止，我们已经通过五个不同的GMKF收到了WGS 共1,486名OFC先证者三人的补助金。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 例数)。到目前为止，最关键的表型数据已经上传到DBGaP(例如，性别， 人口/种族，OFC类型)，但这些研究还提供了丰富的其他表型数据 (例如，有关OFC出生缺陷、孕产史、内科/手术史等的详细信息) 这些项目的可用数据。该项目的目标是制作额外的语义精选数据 通过GMKF向研究界提供OFC研究的要素，以扩大 GMKF口面部裂三联征数据的范围和价值及便于交叉研究 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.