title: Genetics, genomics, and their relevance to pathology and therapy.
abstract: Genetic and genomic investigations are a starting point for the study of human disease, seeking to discover causative variants relevant to disease pathophysiology. Over the past 5 years, massively parallel, high-throughput, next-generation sequencing techniques have revolutionized genetics and genomics, identifying the causes of many Mendelian diseases. The application of whole-genome sequencing and whole-exome sequencing to large populations has produced several publicly available sequence datasets that have revealed the scope of human genetic variation and have contributed to important methodological advances in the study of both common and rare genetic variants in genetically complex diseases. The importance of noncoding genetic variation has been highlighted by the Encyclopedia of DNA Elements (ENCODE) project and National Institutes of Health (NIH) Roadmap Epigenomics Program and integrated analyses of these datasets, together with disease-specific datasets, will provide an important and powerful tool for determining the mechanisms through which disease-associated, noncoding variation influences disease risk.
authors: National Institute of Arthritis, Musculoskeletal, and Skin Diseases, NIH, DHHS, 9000 Rockville Pike, Building 10, Room 10C101A, MSC 1560, Bethesda, MD 20892-1560, USA. Electronic address: michael.ombrello@nih.gov.
authors: Michael J
authors: MJ
authors: Ombrello
authors: National Institute of Arthritis, Musculoskeletal, and Skin Diseases, NIH, DHHS, 9000 Rockville Pike, Building 10, Room 10-CRC/1-5256, MSC 1102, Bethesda, MD 20892-1102, USA. Electronic address: keith.sikora@nih.gov.
authors: Keith A
authors: KA
authors: Sikora
authors: National Human Genome Research Institute, NIH, DHHS, 9000 Rockville Pike, Building 50, Room 5222, MSC 8002, Bethesda, MD 20892-8002, USA. Electronic address: daniel.kastner@nih.gov.
authors: Daniel L
authors: DL
authors: Kastner
mesh_terms: D055106:Genome-Wide Association Study; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D057182:Mendelian Randomization Analysis; D009154:Mutation; D012216:Rheumatic Diseases / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D014481:United States
keywords: Genome-wide association study; Pediatric rheumatology; Somatic mosaicism; Targeted deep resequencing; lncRNA; miRNA