The primary aim of the proposed project is to perform a large-scale survey to identify coding-region single-nucleotide polymorphisms (cSNPs) in 5,000 human genes. The survey will cover approximately 8.5 Mb of sequence on 80 chromosomes (representing a total of about 680 Mb) and is expected to result in the identification of at least 20,000 cSNPs. The coding region of each gene will be amplified by RT-PCR from 40 individuals and the resulting products will be screened for polymorphisms by two independent methods: (a) high-density oligoinucleotide arrays (DNA chips) and (b) denaturing high-pressure liquid chromatography (dHPLC). All genes will be screened by both methods. The use of two screening methods provides high sensitivity to ensure that the vast majority of cSNPs are identified. It also yields a continual cross-check on accuracy, allowing weaknesses of each method to be identified and improvements made. Based on polymorphism frequencies observed in our preliminary studies, the survey is expected to identify at least 20,000 cSNPs with approximately 45 percent encoding an alteration in amino acid sequence. The cSNPs should provide a valuable resource for studying disease association. To facilitate this, all information (including sequence change, effect on protein sequence, observed allele frequencies, etc.) will be promptly deposited on our web site and in national databases and all cSNPs will be made freely available for research.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
3R01HG001953-01S1
Application #
6156267
Study Section
Special Emphasis Panel (ZHG1 (O1))
Program Officer
Brooks, Lisa
Project Start
1999-03-10
Project End
2002-02-28
Budget Start
1999-03-10
Budget End
2000-02-29
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Whitehead Institute for Biomedical Research
Department
Type
DUNS #
076580745
City
Cambridge
State
MA
Country
United States
Zip Code
02142
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Warrington, Janet A; Shah, Nila A; Chen, Xiyin et al. (2002) New developments in high-throughput resequencing and variation detection using high density microarrays. Hum Mutat 19:402-9