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In genetics and bioinformatics, a single-nucleotide polymorphism is a germline substitution of a single nucleotide at a specific position in the genome that is present in a sufficiently large fraction of considered population.
The International HapMap Project was an organization that aimed to develop a haplotype map (HapMap) of the human genome, to describe the common patterns of human genetic variation. HapMap is used to find genetic variants affecting health, disease and responses to drugs and environmental factors. The information produced by the project is made freely available for research.
A DNA segment is identical by state (IBS) in two or more individuals if they have identical nucleotide sequences in this segment. An IBS segment is identical by descent (IBD) in two or more individuals if they have inherited it from a common ancestor without recombination, that is, the segment has the same ancestral origin in these individuals. DNA segments that are IBD are IBS per definition, but segments that are not IBD can still be IBS due to the same mutations in different individuals or recombinations that do not alter the segment.
In molecular biology, SNP array is a type of DNA microarray which is used to detect polymorphisms within a population. A single nucleotide polymorphism (SNP), a variation at a single site in DNA, is the most frequent type of variation in the genome. Around 335 million SNPs have been identified in the human genome, 15 million of which are present at frequencies of 1% or higher across different populations worldwide.
In genomics, a genome-wide association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.
The interleukin-23 receptor is a type I cytokine receptor. It is encoded in human by the IL23R gene. In complex with the interleukin-12 receptor β1 subunit (IL-12Rβ1), it is activated by the cytokine interleukin 23 (IL-23). The IL23R mRNA is 2.8 kilobases in length and includes 12 exons. The translated protein contains 629 amino acids; it is a type I penetrating protein and includes a signal peptide, an N-terminal fibronectin III-like domain and an intracellular part that contains three potential tyrosine phosphorylation domains. There are 24 IL23R splice variants in mitogen-activated lymphocytes. IL23R includes some single-nucleotide polymorphisms in the region encoding the domain that binds IL-23, which may lead to differences between people in Th17 activation. There is also a variant of IL-23R that consists of just the extracellular part and is known as soluble IL-23R. This form can compete with the membrane-bound form to bind IL-23, modulating the Th17 immune response and regulation of inflammation and immune function.
Mark Lathrop is a Canadian Biostatistician. He headed the Center for the Study of Human Polymorphisms, but returned to Canada as Scientific Director at McGill University and Genome Quebec's Innovation Centre in 2011.
Behavioural genetics, also referred to as behaviour genetics, is a field of scientific research that uses genetic methods to investigate the nature and origins of individual differences in behaviour. While the name "behavioural genetics" connotes a focus on genetic influences, the field broadly investigates the extent to which genetic and environmental factors influence individual differences, and the development of research designs that can remove the confounding of genes and environment. Behavioural genetics was founded as a scientific discipline by Francis Galton in the late 19th century, only to be discredited through association with eugenics movements before and during World War II. In the latter half of the 20th century, the field saw renewed prominence with research on inheritance of behaviour and mental illness in humans, as well as research on genetically informative model organisms through selective breeding and crosses. In the late 20th and early 21st centuries, technological advances in molecular genetics made it possible to measure and modify the genome directly. This led to major advances in model organism research and in human studies, leading to new scientific discoveries.
Exome sequencing, also known as whole exome sequencing (WES), is a genomic technique for sequencing all of the protein-coding regions of genes in a genome. It consists of two steps: the first step is to select only the subset of DNA that encodes proteins. These regions are known as exons—humans have about 180,000 exons, constituting about 1% of the human genome, or approximately 30 million base pairs. The second step is to sequence the exonic DNA using any high-throughput DNA sequencing technology.
Genomic structural variation is the variation in structure of an organism's chromosome. It consists of many kinds of variation in the genome of one species, and usually includes microscopic and submicroscopic types, such as deletions, duplications, copy-number variants, insertions, inversions and translocations. Originally, a structure variation affects a sequence length about 1kb to 3Mb, which is larger than SNPs and smaller than chromosome abnormality. However, the operational range of structural variants has widened to include events > 50bp. The definition of structural variation does not imply anything about frequency or phenotypical effects. Many structural variants are associated with genetic diseases, however many are not. Recent research about SVs indicates that SVs are more difficult to detect than SNPs. Approximately 13% of the human genome is defined as structurally variant in the normal population, and there are at least 240 genes that exist as homozygous deletion polymorphisms in human populations, suggesting these genes are dispensable in humans. Rapidly accumulating evidence indicates that structural variations can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.
CDKN2B-AS, also known as ANRIL is a long non-coding RNA consisting of 19 exons, spanning 126.3kb in the genome, and its spliced product is a 3834bp RNA. It is located within the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster, in the antisense direction. Single nucleotide polymorphisms (SNPs) which alter the expression of CDKN2B-AS are associated with human healthy life expectancy, as well as with multiple diseases, including coronary artery disease, diabetes and many cancers. It binds to chromobox 7 (CBX7) within the polycomb repressive complex 1 and to SUZ12, a component of polycomb repression complex 2 and through these interactions is involved in transcriptional repression.
The missing heritability problem is the fact that single genetic variations cannot account for much of the heritability of diseases, behaviors, and other phenotypes. This is a problem that has significant implications for medicine, since a person's susceptibility to disease may depend more on the combined effect of all the genes in the background than on the disease genes in the foreground, or the role of genes may have been severely overestimated.
David Matthew Altshuler is a clinical endocrinologist and human geneticist. He is Executive Vice President, Global Research and Chief Scientific Officer at Vertex Pharmaceuticals. Prior to joining Vertex in 2014, he was at the Broad Institute of Harvard and MIT, and was a Professor of Genetics and Medicine at Harvard Medical School, and in the Department of Biology at Massachusetts Institute of Technology. He was also a faculty member in the Department of Molecular Biology, Center for Human Genetic Research, and the Diabetes Unit, all at Massachusetts General Hospital. He was one of four Founding Core Members of the Broad Institute, and served as the Institute's Deputy Director, Chief Academic Officer, and Director of the Program in Medical and Population Genetics.
Phosphatase and actin regulator 1 (PHACTR1) is a protein that in humans is encoded by the PHACTR1 gene on chromosome 6. It is most significantly expressed in the globus pallidus of the brain. PHACTR1 is an actin and protein phosphatase 1 (PP1) binding protein that binds actin and regulates the reorganization of the actin cytoskeleton. This protein has been associated with coronary artery disease and migraines through genome-wide association studies. The PHACTR1 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.
Project MinE is an independent large scale whole genome research project that was initiated by 2 patients with amyotrophic lateral sclerosis and started on World ALS Day, June 21, 2013.
A rare variant is a genetic variant which occurs at low frequency in a population. Rare variants play a significant role in both complex and Mendelian disease and are responsible for a portion of the missing heritability of complex diseases. The theoretical case for a significant role of rare variants is that alleles that strongly predispose an individual to disease will be kept at low frequencies in populations by purifying selection. Rare variants are increasingly being studied, as a consequence of whole exome and whole genome sequencing efforts. While these variants are individually infrequent in populations, there are many in human populations, and they can be unique to specific populations. They are more likely to be deleterious than common variants, as a result of rapid population growth and weak purifying selection. They have been suspected of acting independently or along with common variants to cause disease states.
Single nucleotide polymorphism annotation is the process of predicting the effect or function of an individual SNP using SNP annotation tools. In SNP annotation the biological information is extracted, collected and displayed in a clear form amenable to query. SNP functional annotation is typically performed based on the available information on nucleic acid and protein sequences.
Cas scaffolding protein family member 4 is a protein that in humans is encoded by the CASS4 gene.
Structural variation in the human genome is operationally defined as genomic alterations, varying between individuals, that involve DNA segments larger than 1 kilo base (kb), and could be either microscopic or submicroscopic. This definition distinguishes them from smaller variants that are less than 1 kb in size such as short deletions, insertions, and single nucleotide variants.
Andre Franke, born on 16 October 1978, is a geneticist, academic, and university professor. He is a Full W3 Professor of Molecular Medicine at the Christian-Albrechts-University of Kiel, and a managing director at the Institute of Clinical Molecular Biology.
References
- ↑ Expanded high-resolution genetic study of 109 Swedish families with Alzheimer's disease, Anna Sillén, Jorge Andrade, Lena Lilius, Charlotte Forsell, Karin Axelman, Jacob Odeberg, Bengt Winblad and Caroline Graff, European Journal of Human Genetics (2008) 16, 202–208; doi : 10.1038/sj.ejhg.5201946; published online 24 October 2007
- ↑ Duerr, R. H.; Taylor, K. D.; Brant, S. R.; Rioux, J. D.; Silverberg, M. S.; Daly, M. J.; Steinhart, A. H.; Abraham, C.; Regueiro, M.; Griffiths, A.; Dassopoulos, T.; Bitton, A.; Yang, H.; Targan, S.; Datta, L. W.; Kistner, E. O.; Schumm, L. P.; Lee, A. T.; Gregersen, P. K.; Barmada, M. M.; Rotter, J. I.; Nicolae, D. L.; Cho, J. H. (2006). "A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene". Science. 314 (5804): 1461–1463. Bibcode:2006Sci...314.1461D. doi:10.1126/science.1135245. ISSN 0036-8075. PMC 4410764 . PMID 17068223.
- ↑ Levy, Daniel; Ehret, Georg B; Rice, Kenneth; Verwoert, Germaine C; Launer, Lenore J; Dehghan, Abbas; Glazer, Nicole L; Morrison, Alanna C; Johnson, Andrew D; Aspelund, Thor; Aulchenko, Yurii; Lumley, Thomas; Köttgen, Anna; Vasan, Ramachandran S; Rivadeneira, Fernando; Eiriksdottir, Gudny; Guo, Xiuqing; Arking, Dan E; Mitchell, Gary F; Mattace-Raso, Francesco U S; Smith, Albert V; Taylor, Kent; Scharpf, Robert B; Hwang, Shih-Jen; Sijbrands, Eric J G; Bis, Joshua; Harris, Tamara B; Ganesh, Santhi K; O'Donnell, Christopher J; Hofman, Albert; Rotter, Jerome I; Coresh, Josef; Benjamin, Emelia J; Uitterlinden, André G; Heiss, Gerardo; Fox, Caroline S; Witteman, Jacqueline C M; Boerwinkle, Eric; Wang, Thomas J; Gudnason, Vilmundur; Larson, Martin G; Chakravarti, Aravinda; Psaty, Bruce M; van Duijn, Cornelia M (2009). "Genome-wide association study of blood pressure and hypertension". Nature Genetics. 41 (6): 677–687. doi:10.1038/ng.384. ISSN 1061-4036. PMC 2998712 . PMID 19430479.
- ↑ Storey, John D.; Raychaudhuri, Soumya; Plenge, Robert M.; Rossin, Elizabeth J.; Ng, Aylwin C. Y.; Purcell, Shaun M.; Sklar, Pamela; Scolnick, Edward M.; Xavier, Ramnik J.; Altshuler, David; Daly, Mark J. (2009). "Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions". PLOS Genetics. 5 (6): e1000534. doi: 10.1371/journal.pgen.1000534 . ISSN 1553-7404. PMC 2694358 . PMID 19557189.
- ↑ Seshadri, Sudha (2010). "Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease". JAMA. 303 (18): 1832–1840. doi:10.1001/jama.2010.574. ISSN 0098-7484. PMC 2989531 . PMID 20460622.
- ↑ Zeggini, Eleftheria; Scott, Laura J; Saxena, Richa; Voight, Benjamin F; Marchini, Jonathan L; Hu, Tianle; de Bakker, Paul IW; Abecasis, Gonçalo R; Almgren, Peter; Andersen, Gitte; Ardlie, Kristin; Boström, Kristina Bengtsson; Bergman, Richard N; Bonnycastle, Lori L; Borch-Johnsen, Knut; Burtt, Noël P; Chen, Hong; Chines, Peter S; Daly, Mark J; Deodhar, Parimal; Ding, Chia-Jen; Doney, Alex S F; Duren, William L; Elliott, Katherine S; Erdos, Michael R; Frayling, Timothy M; Freathy, Rachel M; Gianniny, Lauren; Grallert, Harald; Grarup, Niels; Groves, Christopher J; Guiducci, Candace; Hansen, Torben; Herder, Christian; Hitman, Graham A; Hughes, Thomas E; Isomaa, Bo; Jackson, Anne U; Jørgensen, Torben; Kong, Augustine; Kubalanza, Kari; Kuruvilla, Finny G; Kuusisto, Johanna; Langenberg, Claudia; Lango, Hana; Lauritzen, Torsten; Li, Yun; Lindgren, Cecilia M; Lyssenko, Valeriya; Marvelle, Amanda F; Meisinger, Christa; Midthjell, Kristian; Mohlke, Karen L; Morken, Mario A; Morris, Andrew D; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Palmer, Colin NA; Payne, Felicity; Perry, John R B; Pettersen, Elin; Platou, Carl; Prokopenko, Inga; Qi, Lu; Qin, Li; Rayner, Nigel W; Rees, Matthew; Roix, Jeffrey J; Sandbæk, Anelli; Shields, Beverley; Sjögren, Marketa; Steinthorsdottir, Valgerdur; Stringham, Heather M; Swift, Amy J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Timpson, Nicholas J; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Walker, Mark; Watanabe, Richard M; Weedon, Michael N; Willer, Cristen J; Illig, Thomas; Hveem, Kristian; Hu, Frank B; Laakso, Markku; Stefansson, Kari; Pedersen, Oluf; Wareham, Nicholas J; Barroso, Inês; Hattersley, Andrew T; Collins, Francis S; Groop, Leif; McCarthy, Mark I; Boehnke, Michael; Altshuler, David (2008). "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes". Nature Genetics. 40 (5): 638–645. doi:10.1038/ng.120. ISSN 1061-4036. PMC 2672416 . PMID 18372903.