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

摘要

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.