Speaker: Jack Simpson, Center for Medical and Molecular Genetics, AFIP, Rockville, MD

Topic: Single Nucleotide Polymorphism Analysis by Mass Spectrometry

Place: Building 426, Conference Room, NCI-Frederick, Frederick, MD

Time: Wednesday, March 22, 2000, at 2:00 PM

Abstract: The molecular basis for certain diseases is now well known and was first recognized by Linus Pauling through his work on sickle cell anemia. Our laboratory has a long standing interest in molecular diseases and specifically, those that may arise from a single nucleotide change or polymorphism (SNPs) on the genome level. Hereditary hemochromatosis (HH) is one such disease.

HH is an autosomal recessive disorder, which results from abnormal iron metabolism and is one of the most prevalent hereditary diseases. The disease is thought to be the result of two SNPs in the HFE gene, C to T (C282Y) and G to C (H63D). Often misdiagnosed, HH can result in extensive organ damage or death if left untreated. If detected before the onset of symptoms, however, it can be effectively treated with regular phlebotomy. This treatment is so effective at reducing the iron overload that a normal life expectancy can be achieved.

We have focused recently on method development for the detection of HH SNPs in blood, with the goal of providing a method that would be suitable for high throughput screening. Towards this end we are currently evaluating MALDI-TOF/MS analysis of single nucleotide extension products for the detection of HH. Our current approaches and results will be presented along with a general discussion of SNP analysis by mass spectrometry.