An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People-Reference-Cited by-同舟云学术

An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People

Published:2012-07-06 Issue:6090 Volume:337 Page:100-104
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Nelson Matthew R.¹,Wegmann Daniel²,Ehm Margaret G.¹,Kessner Darren²,St. Jean Pamela¹,Verzilli Claudio³,Shen Judong¹,Tang Zhengzheng⁴,Bacanu Silviu-Alin¹,Fraser Dana¹,Warren Liling¹,Aponte Jennifer¹,Zawistowski Matthew⁵,Liu Xiao⁶,Zhang Hao⁶,Zhang Yong⁶,Li Jun⁷,Li Yun⁴,Li Li¹,Woollard Peter³,Topp Simon³,Hall Matthew D.³,Nangle Keith¹,Wang Jun⁶⁸,Abecasis Gonçalo⁵,Cardon Lon R.⁹,Zöllner Sebastian⁵¹⁰,Whittaker John C.³,Chissoe Stephanie L.¹,Novembre John²,Mooser Vincent⁹

Affiliation:

1. Department of Quantitative Sciences, GlaxoSmithKline (GSK), Research Triangle Park, NC 27709, USA.

2. Department of Ecology and Evolutionary Biology, University of California–Los Angeles, Los Angeles, CA 90095, USA.

3. Department of Quantitative Sciences, GSK, Stevenage SG1 2NY, UK.

4. Department of Genetics and Biostatistics, University of North Carolina–Chapel Hill, Chapel Hill, NC 27599, USA.

5. Department of Biostatistics, University of Michigan–Ann Arbor, Ann Arbor, MI 48109, USA.

6. BGI, Shenzhen 518083, China.

7. Department of Human Genetics, University of Michigan–Ann Arbor, Ann Arbor, MI 48109, USA.

8. Department of Biology, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen 3393 9524, Denmark.

9. Department of Quantitative Sciences, GSK, Upper Merion, PA 19406, USA.

10. Department of Psychiatry, University of Michigan–Ann Arbor, Ann Arbor, MI 48109, USA.

Abstract

A Deep Look Into Our Genes Recent debates have focused on the degree of genetic variation and its impact upon health at the genomic level in humans (see the Perspective by Casals and Bertranpetit ). Tennessen et al. (p. 64 , published online 17 May), looking at all of the protein-coding genes in the human genome, and Nelson et al. (p. 100 , published online 17 May), looking at genes that encode drug targets, address this question through deep sequencing efforts on samples from multiple individuals. The findings suggest that most human variation is rare, not shared between populations, and that rare variants are likely to play a role in human health.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference84 articles.

1. Are Rare Variants Responsible for Susceptibility to Complex Diseases?

2. Most Rare Missense Alleles Are Deleterious in Humans: Implications for Complex Disease and Association Studies

3. The functional spectrum of low-frequency coding variation

4. Finding the missing heritability of complex diseases

5. Missing heritability and strategies for finding the underlying causes of complex disease

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