Rare disease susceptibility alleles in children with Crohn disease

The overall goal of this proposed project is to identify rare genetic variants contributing to childhood onset-Crohn disease. Crohn disease is a chronic inflammatory disorder of the gastrointestinal tract of unclear etiology and no known cure. Affected children suffer from diarrhea, abdominal pain, growth disturbances, and an impaired quality of life. The identified Crohn disease susceptibility alleles have improved our understanding of Crohn disease pathogenesis. However, the identified susceptibility alleles do not account for the observed heritability, nor have disease-causing alleles in many genomic regions been identified. For the proposed studies, we will use 1) existing DNA samples collected from high-risk Crohn kindreds identified using the extensive genealogical records available only in Utah, 2) existing DNA samples obtained from very young children with Crohn disease and their parents, and 3) existing DNA samples obtained from healthy controls that are free of a personal or family history of autoimmune disorders.]]>
The affected child in the current study was selected from > 300 children with Crohn disease onset younger than age 12 years. Crohn disease was defined using standard clinical, radiographic, endoscopic, and histological criteria described in the NIDDK IBD Genetics Consortium Phenotyping Form and Manual. The source of controls are DNA samples selected from ~1000 samples that we collected from healthy adults. At enrollment, we screened these individuals for a personal or family history of 15 autoimmune conditions, and a personal or family history of diarrhea and/or unexplained rectal bleeding and excluded them if they had any of these present.]]>