Human genes involved in copy number variation: mechanisms of origin, functional effects and implications for disease

被引:54
作者
de Smith, A. J. [1 ]
Walters, R. G. [1 ]
Froguel, P. [1 ,2 ]
Blakemore, A. I. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sect Genom Med, London, England
[2] Inst Pasteur, Inst Biol, CNRS 8090, F-59019 Lille, France
基金
英国医学研究理事会;
关键词
D O I
10.1159/000184688
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Copy number variants (CNVs) overlap over 7000 genes, many of which are pivotal in biological pathways. The implications of this are profound, with consequences for evolutionary studies, population genetics, gene function and human phenotype, including elucidation of genetic susceptibility to major common diseases, the heritability of which has thus far defied full explanation. Even though this research is still in its infancy, CNVs have already been associated with a number of monogenic, syndromic and complex diseases: the development of high throughput and high resolution techniques for CNV screening is likely to bring further new insights into the contribution of copy number variation to common diseases. Amongst genes overlapped by CNVs, significant enrichments for certain gene ontology categories have been identified, including those related to immune responses and interactions with the environment. Genes in both of these categories are thought to be important in evolutionary adaptation and to be particular targets of natural selection. Thus, a full appreciation of copy number variation may be important for our understanding of human evolution. Copyright (C) 2009 S. Karger AG, Basel
引用
收藏
页码:17 / 26
页数:10
相关论文
共 88 条
[21]  
Freeman SB, 1998, AM J MED GENET, V80, P213, DOI 10.1002/(SICI)1096-8628(19981116)80:3<213::AID-AJMG6>3.3.CO
[22]  
2-#
[23]   The International HapMap Project [J].
Gibbs, RA ;
Belmont, JW ;
Hardenbol, P ;
Willis, TD ;
Yu, FL ;
Yang, HM ;
Ch'ang, LY ;
Huang, W ;
Liu, B ;
Shen, Y ;
Tam, PKH ;
Tsui, LC ;
Waye, MMY ;
Wong, JTF ;
Zeng, CQ ;
Zhang, QR ;
Chee, MS ;
Galver, LM ;
Kruglyak, S ;
Murray, SS ;
Oliphant, AR ;
Montpetit, A ;
Hudson, TJ ;
Chagnon, F ;
Ferretti, V ;
Leboeuf, M ;
Phillips, MS ;
Verner, A ;
Kwok, PY ;
Duan, SH ;
Lind, DL ;
Miller, RD ;
Rice, JP ;
Saccone, NL ;
Taillon-Miller, P ;
Xiao, M ;
Nakamura, Y ;
Sekine, A ;
Sorimachi, K ;
Tanaka, T ;
Tanaka, Y ;
Tsunoda, T ;
Yoshino, E ;
Bentley, DR ;
Deloukas, P ;
Hunt, S ;
Powell, D ;
Altshuler, D ;
Gabriel, SB ;
Qiu, RZ .
NATURE, 2003, 426 (6968) :789-796
[24]   The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility [J].
Gonzalez, E ;
Kulkarni, H ;
Bolivar, H ;
Mangano, A ;
Sanchez, R ;
Catano, G ;
Nibbs, RJ ;
Freedman, BI ;
Quinones, MP ;
Bamshad, MJ ;
Murthy, KK ;
Rovin, BH ;
Bradley, W ;
Clark, RA ;
Anderson, SA ;
O'Connell, RJ ;
Agan, BK ;
Ahuja, SS ;
Bologna, R ;
Sen, L ;
Dolan, MJ ;
Ahuja, SK .
SCIENCE, 2005, 307 (5714) :1434-1440
[25]   The DNA sequence and biology of human chromosome 19 [J].
Grimwood, J ;
Gordon, LA ;
Olsen, A ;
Terry, A ;
Schmutz, J ;
Lamerdin, J ;
Hellsten, U ;
Goodstein, D ;
Couronne, O ;
Gyamfi, MT ;
Aerts, A ;
Altherr, M ;
Ashworth, L ;
Bajorek, E ;
Black, S ;
Branscomb, E ;
Caenepeel, S ;
Carrano, A ;
Caoile, C ;
Chan, YM ;
Christensen, M ;
Cleland, CA ;
Copeland, A ;
Dalin, E ;
Dehal, P ;
Denys, M ;
Detter, JC ;
Escobar, J ;
Flowers, D ;
Fotopulos, D ;
Garcia, C ;
Georgescu, AM ;
Glavina, T ;
Gomez, M ;
Gonzales, E ;
Groza, M ;
Hammon, N ;
Hawkins, T ;
Haydu, L ;
Ho, I ;
Huang, W ;
Israni, S ;
Jett, J ;
Kadner, K ;
Kimball, H ;
Kobayashi, A ;
Larionov, V ;
Leem, SH ;
Lopez, F ;
Lou, YL .
NATURE, 2004, 428 (6982) :529-535
[26]   Distribution and functional impact of DNA copy number variation in the rat [J].
Guryev, Victor ;
Saar, Kathrin ;
Adamovic, Tatjana ;
Verheul, Mark ;
Van Heesch, Sebastiaan A. A. C. ;
Cook, Stuart ;
Pravenec, Michal ;
Aitman, Timothy ;
Jacob, Howard ;
Shull, James D. ;
Hubner, Norbert ;
Cuppen, Edwin .
NATURE GENETICS, 2008, 40 (05) :538-545
[27]  
HAUPTMANN G, 1974, B I SIEROTER MILAN, V53, P228
[28]   Common deletions and SNPs are in linkage disequilibrium in the human genome [J].
Hinds, DA ;
Kloek, AP ;
Jen, M ;
Chen, XY ;
Frazer, KA .
NATURE GENETICS, 2006, 38 (01) :82-85
[29]   Psoriasis is associated with increased β-defensin genomic copy number [J].
Hollox, Edward J. ;
Huffmeier, Ulrike ;
Zeeuwen, Patrick L. J. M. ;
Palla, Raquel ;
Lascorz, Jesús ;
Rodijk-Olthuis, Diana ;
van de Kerkhof, Peter C. M. ;
Traupe, Heiko ;
de Jongh, Gys ;
den Heijer, Martin ;
Reis, Andre ;
Armour, John A. L. ;
Schalkwijk, Joost .
NATURE GENETICS, 2008, 40 (01) :23-25
[30]   Extensive normal copy number variation of a β-defensin antimicrobial-gene cluster [J].
Hollox, EJ ;
Armour, JAL ;
Barber, JCK .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (03) :591-600