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Physiol. Genomics (July 9, 2002). doi:10.1152/physiolgenomics.00030.2002
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Articles in PresS, published online ahead of print July 9, 2002
Physiol Genomics, 10.1152/physiolgenomics.00030.2002
Submitted on March 21, 2002
Accepted on July 8, 2002

Novel and Non-detectable Human Signaling Protein Polymorphisms

Roy A Lynch1, Lynne Wagoner1, Shunan Li1, Li Sparks1, Jeffery Molkentin1, and Gerald W Dorn II1*

1 Division of Cardiology, University of Cincinnati Medical Center, Cincinnati, Ohio, USA

* To whom correspondence should be addressed. E-mail: dorngw{at}ucmail.uc.edu.

The frequency of single nucleotide polymorphisms in downstream signaling proteins was determined by combination heteroduplex high performance liquid chromatography and double stranded sequencing of genomic DNA from 96 to 144 congestive heart failure (CHF) patients. Analysis of fifty-six coding exons in nine signaling genes revealed seventeen novel and eight previously reported synonymous (no change in amino acid) SNPs, as well as one novel non-synonymous SNP in the Rad small G-protein. Because this initial analysis failed to detect numerous SNPs reported in the NCBI and Celera databases, double strand sequencing of relevant exons from 74 to 91 CHF patients was used to confirm the absence of ten previously reported non-synonymous SNPs. Our results show that synonymous SNPs are frequent in signaling protein genes, whereas non-synonymous SNPs are rare, suggesting a high degree of evolutionary conservation among these downstream signaling molecules. Comparisons of our results to the NCBI and Celera databases indicates that 56% of their SNP entries are not detected in our cohort. Importantly, while 31% of database SNPs were verified, 69% of SNPs detected in our cohort are not included in these databases. These findings indicate that caution may be warranted in relying exclusively on SNP databases as catalogs for polymorphic signaling protein genes.




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