HUM-MOLGEN DIAGnostics/Clinical Research


Fragile X locus (FMR1)/call for collaboration

I am working on a Phase II SBIR application to the NIH focused on novel methods for high-throughput genotyping in triplet repeat expansion disorders. In one specific section of the proposal, we describe some novel separation methods we would like to test for differentiating punctuated (low risk) and non-punctuated (high-risk) premutation alleles at the Fragile X locus (FMR1). Due to the long size of the disease-causing alleles at this locus, most diagnostic laboratories are currently not using PCR for Fragile X. However, premutation alleles are reported to amplify by PCR. We are seeking access to FMR1 PCR products from premutation alleles to include profiles in the Phase II application which is due December 15, 1996. We have developed a novel DNA separation matrix that allows separation of 80 bp- 40 kb in very short runs on the instrument system that I am validating (See Mansfield et al. 1996 Am. J. Hum. Genetics 59(4): A307.) Our detection limits are approximately 2-3 orders of magnitude lower than other instrument systems. This should permit non-abundant PCR products to be detected. If you have PCR product from FMR1 premutation alleles that we might test for this purpose, I would very much like to collaborate.

Elaine S. Mansfield, Ph.D.
Molecular Dynamics, Inc.