@article{Zheng2012, abstract = {Defective Gene Detective Identifying genes that give rise to diseases is one of the major goals of sequencing human genomes. However, putative loss-of-function genes, which are often some of the first identified targets of genome and exome sequencing, have often turned out to be sequencing errors rather than true genetic variants. In order to identify the true scope of loss-of-function genes within the human genome, MacArthur et al. (p. 823 ; see the Perspective by Quintana-Murci ) extensively validated the genomes from the 1000 Genomes Project, as well as an additional European individual, and found that the average person has about 100 true loss-of-function alleles of which approximately 20 have two copies within an individual. Because many known disease-causing genes were identified in “normal” individuals, the process of clinical sequencing needs to reassess how to identify likely causative alleles. }, author = {Zheng, X. and Zhou, Y. and Zheng Bradley, X. and Zöllner, S. and Zilversmit, M. and Dg, MacArthur and MacArthur, Daniel G. and Jk, Pickrell and Sb, Montgomery and Ma, DePristo and Jin, M. and Dr, Carvalho Silva and Balasubramanian, Suganthi and Consortium, Genomes Project and Altshuler, D. and Rm, Durbin and Gr, Abecasis and Frankish, Adam and Dr, Bentley and Chakravarti, A. and Ag, Clark and Fs, Collins and Fm, De La Vega and Donnelly, P. and Huang, Ni and Egholm, M. and Flicek, P. and Sb, Gabriel and Bm, Knoppers and Es, Lander and Lehrach, H. and Morris, James and Er, Mardis and Ga, McVean and Ca, Albers and Da, Nickerson and Peltonen, L. and Aj, Schafer and St, Sherry and Walter, Klaudia and Zd, Zhang and Wang, J. and Wilson, R. and Deiros, D. and Metzker, M. and Df, Conrad and Muzny, D. and Reid, J. and Jostins, Luke and Wheeler, D. and Li, J. and Jian, M. and Li, G. and Li, R. and Liang, H. and Tian, G. and Wang, B. and Habegger, Lukas and Wang, W. and Yang, H. and Zhang, X. and Dl, Altshuler and Ambrogio, L. and Bloom, T. and Cibulskis, K. and Pickrell, Joseph K. and Tj, Fennell and Db, Jaffe and Shefler, E. and Cl, Sougnez and Zhang, Zhengdong D. and Gormley, N. and Humphray, S. and Montgomery, Stephen B. and Kingsbury, Z. and Re, Handsaker and Kokko Gonzales, P. and Stone, J. and Kj, McKernan and Gl, Costa and Ja, Rosenfeld and Albers, Cornelis A. and Zhang, Z. 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A. Wang, J. and Tyler-Smith, Chris and Jk, Pritchard}, doi = {10.1126/science.1215040}, month = {feb}, title = {A systematic survey of loss-of-function variants in human protein-coding genes}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22344438}, year = {2012} }