Rare functional variant

A rare functional variant is a genetic variant which alters gene function, and which occurs at low frequency in a population. Rare variants may play a significant role in complex disease, as well as some Mendelian conditions. Rare variants may be 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.[1] Rare variants are increasingly being studied, as a consequence of 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.[2] They have been suspected of acting independently or along with common variants to cause disease states.[3]

See also

References
  1. Goldstein, DB; Allen, A; Keebler, J; Margulies, EH; Petrou, S; Petrovski, S; Sunyaev, S (July 2013). "Sequencing studies in human genetics: design and interpretation". Nature Reviews Genetics. 14 (7): 460–70. doi:10.1038/nrg3455. PMC 4117319. PMID 23752795.
  2. Nelson, M. R.; Wegmann, D.; Ehm, M. G.; Kessner, D.; St. Jean, P.; Verzilli, C.; Shen, J.; Tang, Z.; Bacanu, S.-A.; Fraser, D.; Warren, L.; Aponte, J.; Zawistowski, M.; Liu, X.; Zhang, H.; Zhang, Y.; Li, J.; Li, Y.; Li, L.; Woollard, P.; Topp, S.; Hall, M. D.; Nangle, K.; Wang, J.; Abecasis, G.; Cardon, L. R.; Zollner, S.; Whittaker, J. C.; Chissoe, S. L.; Novembre, J.; Mooser, V. (17 May 2012). "An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People". Science. 337 (6090): 100–104. Bibcode:2012Sci...337..100N. doi:10.1126/science.1217876. PMC 4319976. PMID 22604722.
  3. Panoutsopoulou, K.; Tachmazidou, I.; Zeggini, E. (6 August 2013). "In search of low-frequency and rare variants affecting complex traits". Human Molecular Genetics. 22 (R1): R16–R21. doi:10.1093/hmg/ddt376. PMC 3782074. PMID 23922232.

Further reading


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