{"corpus_id":9186422,"paper_sha":"ccec7d5fab762800d53ac4d2f58a1f93c0e27ee7","doi":"10.1038/ng0914-1040a","arxiv_id":null,"pmid":21841781,"pmcid":"3171215","mag_id":2106650442,"dblp_id":null,"acl_id":null,"title":"A Copy Number Variation Morbidity Map of Developmental Delay","year":2011,"publication_date":"2011-08-09","venue":"Nature Genetics","journal":{"name":"Nature genetics","pages":"838 - 846","volume":"43"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":66,"citation_count":1323,"influential_citation_count":88,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Child, Preschool","mj":false,"ui":"D002675"},{"d":"Chromosome Mapping","mj":true,"ui":"D002874"},{"d":"Congenital Abnormalities","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D000013"},{"d":"Developmental Disabilities","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D002658"},{"d":"Gene Dosage","mj":true,"ui":"D018628"},{"d":"Genetic Variation","mj":true,"ui":"D014644"},{"d":"Humans","mj":false,"ui":"D006801"}],"chemicals":null,"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that ∼14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.","claims":[{"public_id":"cl_474431dc490a92a3da387eda1708821e","status":"active","text":"Copy number variants are more strongly enriched in individuals with craniofacial anomalies and cardiovascular defects than in those with epilepsy or autism.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_474431dc490a92a3da387eda1708821e"},{"public_id":"cl_f56bb48d9af102b2c2b55c1a22185d84","status":"active","text":"Copy number variants larger than 400 kb account for an estimated 14.2% of disease in children with developmental delay and intellectual disability.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_f56bb48d9af102b2c2b55c1a22185d84"},{"public_id":"cl_998c9b4e80236f69ce1c98da3c586609","status":"active","text":"Fifty-nine pathogenic copy number variants were identified, including 14 new or previously weakly supported candidates.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_998c9b4e80236f69ce1c98da3c586609"},{"public_id":"cl_0f5ae3c7e4a34eb116439e624ee5871a","status":"active","text":"Nine hundred forty candidate dosage-sensitive genes were identified, and methods were developed to opportunistically discover small, disruptive copy number variants in diagnostic array datasets.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_0f5ae3c7e4a34eb116439e624ee5871a"},{"public_id":"cl_e290948ddf0adc9a517f87c513974788","status":"active","text":"The critical interval for several genomic disorders, including 17q21.31 microdeletion syndrome, was refined.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_e290948ddf0adc9a517f87c513974788"}],"concepts":[{"public_id":"co_0a74dadb9052055115cfee1bcd7feb1d","status":"active","name":"autism","description":"A neurodevelopmental condition affecting social communication and behavior.","types":["condition"],"aliases":["autism spectrum 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