1 / 8

Sequencing TRAF1 in patients with rheumatoid arthritis

Sequencing TRAF1 in patients with rheumatoid arthritis. Bruce C. Jobse Medical and Population Genetics Broad Institute. The Purpose of the Experiment. To identify, via sequencing, any novel casual DNA variants capable of explaining increased RA-risk in Humans.

rico
Download Presentation

Sequencing TRAF1 in patients with rheumatoid arthritis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Sequencing TRAF1 in patients with rheumatoid arthritis Bruce C. Jobse Medical and Population Genetics Broad Institute

  2. The Purpose of the Experiment To identify, via sequencing, any novel casual DNA variants capable of explaining increased RA-risk in Humans

  3. What is Rheumatoid Arthritis (RA)? • Chronic autoimmune disorder • Afflicts 1% of adults worldwide • 60% heritable

  4. The TRAF1-C5 Region: Associated to risk of RA • rs3761847 – odds-ratio increase of 1.30 • common allele – found in 30-40% of population • two genes of immunological relevance – TRAF1-C5 1,522 CCP+ RA cases, 1,850 controls (NARAC-I, EIRA-I) 997 CCP+ RA cases, 1,777 controls (NARAC-II, EIRA-II)

  5. Experimental Schema • Generated sequence data: • Coding exons, 5’ UTR, 3’ UTR • 96 patients with RA using Sanger sequencing (Broad) • Automated SNP calling algorithms • Validated sequence data: • Genotyped all novel SNPs in same RA samples • Assessed LD structure • genotyped in CEU HapMap samples • Determined r2 with RA-associated SNP (rs3761847)

  6. Results • 29 SNPs were identified (4.5 kb of sequence) • MAF >5% n=8 all were in dbSNP • MAF <5% n=21 14 were novel • 19 out of 22 were genotyped by Sequenom in same 96 patients • SNPs that failed genotyping did not pass quality control tests • Currently assessing SNPs to validate whether real or artifact • No significant LD with the RA risk variant in HapMap • Assess putative functional SNPs • MAF >5% no missense or functional alleles • MAF <5% 4 novel missense alleles

  7. Conclusion • No DNA variant found that would disrupt transcript-signals or conserved sequence motifs • Further examination of 4 discovered missense SNPs – needs further retesting in the population

  8. Acknowledgements Broad Institute: Eric Lander David Altshuler SRPG Program: Bruce Birren Shawna Young Lucia Vielma Metabolics Group: Candace Guiducci Gabe Crawford Mentor: Robert Plenge

More Related