Published online before print
September 13, 2004
Genome Research, DOI: 10.1101/gr.2730004
Genome Research Vol 0, Issue 2004, gr.2730004, 2004
© 2004 Cold Spring Harbor Laboratory Press
Pattern of Sequence Variation Across 213 Environmental Response Genes
Robert J. Livingston1,
Andrew von Niederhausern2,
Anil G. Jegga3,
Dana C. Crawford1,
Christopher S. Carlson1,
Mark J. Rieder1,
Sivakumar Gowrisankar3,
Bruce J. Aronow3,
Robert B. Weiss2 and
Deborah A. Nickerson1,4
1 Department of Genome Sciences, University of Washington, Seattle, Washington 98195-7730, USA
,
2 Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112-5330, USA
,
3 Division of Pediatric Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229 USA
To promote the clinical and epidemiological studies that improve our understanding of human genetic susceptibility to environmental exposure, the Environmental Genome Project (EGP) has scanned 213 environmental response genes involved in DNA repair, cell cycle regulation, apoptosis, and metabolism for single nucleotide polymorphisms (SNPs). Many of these genes have been implicated by loss-of-function mutations associated with severe diseases attributable to decreased protection of genomic integrity. Therefore, the hypothesis for these studies is that individuals with functionally significant polymorphisms within these genes may be particularly susceptible to genotoxic environmental agents. On average, 20.4 kb of baseline genomic sequence or 86% of each gene, including a substantial amount of introns, all exons, and 1.3 kb upstream and downstream, was scanned for variations in the 90 samples of the Polymorphism Discovery Resource panel. The average nucleotide diversity across the 4.2 MB of these 213 genes is 6.7 x 10-4, or one SNP every 1500 bp, when two random chromosomes are compared. The average candidate environmental response gene contains 26 PHASE inferred haplotypes, 34 common SNPs, 6.2 coding SNPs (cSNPs), and 2.5 nonsynonymous cSNPs. SIFT and Polyphen analysis of 541 nonsynonymous cSNPs identified 57 potentially deleterious SNPs. An additional eight polymorphisms predict altered protein translation. Because these genes represent 1% of all known human genes, extrapolation from these data predicts the total genomic set of cSNPs, nonsynonymous cSNPs, and potentially deleterious nonsynonymous cSNPs. The implications for the use of these data in direct and indirect association studies of environmentally induced diseases are discussed.
Supplemental material is available online at www.genome.org. All sequence data from this study have been submitted to GenBank and are available from our Web site at http://egp.gs.washington.edu and at other sites listed herein.
Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.2730004. Article published online ahead of print in September 2004.
4 Corresponding author.
E-MAIL debnick{at}u.washington.edu; FAX (206) 221-6498.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. J. Marini, J. Gin, J. Ziegle, K. H. Keho, D. Ginzinger, D. A. Gilbert, and J. Rine
The prevalence of folate-remedial MTHFR enzyme variants in humans
PNAS,
June 10, 2008;
105(23):
8055 - 8060.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. D. Keightley and A. Eyre-Walker
Joint Inference of the Distribution of Fitness Effects of Deleterious Mutations and Population Demography Based on Nucleotide Polymorphism Frequencies
Genetics,
December 1, 2007;
177(4):
2251 - 2261.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Torkamani and N. J. Schork
Accurate prediction of deleterious protein kinase polymorphisms
Bioinformatics,
November 1, 2007;
23(21):
2918 - 2925.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Hernandez, S. H. Williamson, L. Zhu, and C. D. Bustamante
Context-Dependent Mutation Rates May Cause Spurious Signatures of a Fixation Bias Favoring Higher GC-Content in Humans
Mol. Biol. Evol.,
October 1, 2007;
24(10):
2196 - 2202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Michiels, P. Danoy, P. Dessen, A. Bera, T. Boulet, C. Bouchardy, M. Lathrop, A. Sarasin, and S. Benhamou
Polymorphism discovery in 62 DNA repair genes and haplotype associations with risks for lung and head and neck cancers
Carcinogenesis,
August 1, 2007;
28(8):
1731 - 1739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Asthana, W. S. Noble, G. Kryukov, C. E. Grant, S. Sunyaev, and J. A. Stamatoyannopoulos
Widely distributed noncoding purifying selection in the human genome
PNAS,
July 24, 2007;
104(30):
12410 - 12415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Jegga, S. Gowrisankar, J. Chen, and B. J. Aronow
PolyDoms: a whole genome database for the identification of non-synonymous coding SNPs with the potential to impact disease
Nucleic Acids Res.,
January 12, 2007;
35(suppl_1):
D700 - D706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Cohen
Genetic Approaches to Coronary Heart Disease
J. Am. Coll. Cardiol.,
October 27, 2006;
48(9_Suppl_A):
A10 - A14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Eyre-Walker, M. Woolfit, and T. Phelps
The Distribution of Fitness Effects of New Deleterious Amino Acid Mutations in Humans
Genetics,
June 1, 2006;
173(2):
891 - 900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Soldevila, A. M. Andres, A. Ramirez-Soriano, T. Marques-Bonet, F. Calafell, A. Navarro, and J. Bertranpetit
The prion protein gene in humans revisited: Lessons from a worldwide resequencing study
Genome Res.,
February 1, 2006;
16(2):
231 - 239.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Taylor, Z.-L. Xu, N. L. Kaplan, and R. W. Morris
How Well Do HapMap Haplotypes Identify Common Haplotypes of Genes? A Comparison with Haplotypes of 334 Genes Resequenced in the Environmental Genome Project
Cancer Epidemiol. Biomarkers Prev.,
January 1, 2006;
15(1):
133 - 137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. R. Freimuth, M. Xiao, S. Marsh, M. Minton, N. Addleman, D. J. Van Booven, H. L. McLeod, and P.-Y. Kwok
Polymorphism discovery in 51 chemotherapy pathway genes
Hum. Mol. Genet.,
December 1, 2005;
14(23):
3595 - 3603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Clark, M. J. Hubisz, C. D. Bustamante, S. H. Williamson, and R. Nielsen
Ascertainment bias in studies of human genome-wide polymorphism
Genome Res.,
November 1, 2005;
15(11):
1496 - 1502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Lawrence, D. M. Evans, A. P. Morris, X. Ke, S. Hunt, M. Paolucci, J. Ragoussis, P. Deloukas, D. Bentley, and L. R. Cardon
Genetically indistinguishable SNPs and their influence on inferring the location of disease-associated variants
Genome Res.,
November 1, 2005;
15(11):
1503 - 1510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Carlson, D. J. Thomas, M. A. Eberle, J. E. Swanson, R. J. Livingston, M. J. Rieder, and D. A. Nickerson
Genomic regions exhibiting positive selection identified from dense genotype data
Genome Res.,
November 1, 2005;
15(11):
1553 - 1565.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Zaitlen, H. M. Kang, M. L. Feolo, S. T. Sherry, E. Halperin, and E. Eskin
Inference and analysis of haplotypes from combined genotyping studies deposited in dbSNP
Genome Res.,
November 1, 2005;
15(11):
1594 - 1600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Davis and N. G. Hord
Nutritional "Omics" Technologies for Elucidating the Role(s) of Bioactive Food Components in Colon Cancer Prevention
J. Nutr.,
November 1, 2005;
135(11):
2694 - 2697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Williamson, R. Hernandez, A. Fledel-Alon, L. Zhu, R. Nielsen, and C. D. Bustamante
Simultaneous inference of selection and population growth from patterns of variation in the human genome
PNAS,
May 31, 2005;
102(22):
7882 - 7887.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Johnson, J. Houck, and C. Chen
Screening for Deleterious Nonsynonymous Single-Nucleotide Polymorphisms in Genes Involved in Steroid Hormone Metabolism and Response
Cancer Epidemiol. Biomarkers Prev.,
May 1, 2005;
14(5):
1326 - 1329.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. R. Bhangale, M. J. Rieder, R. J. Livingston, and D. A. Nickerson
Comprehensive identification and characterization of diallelic insertion-deletion polymorphisms in 330 human candidate genes
Hum. Mol. Genet.,
January 1, 2005;
14(1):
59 - 69.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
