Enter Genomics
Around the same time, Vamsi Mootha, a young physician postdoctoral fellow of Lander and an expert on mitochondrial biology, asked to tackle the problem by applying the new tools of genomics. Using a three-pronged approach, Mootha begain by searching the latest sequence data on the mouse and human genomes. He collected comprehensive information on all the known and predicted genes in the region on chromosome 2 where the gene was thought to lie. He found 30 distinct genes whose function was not known.
Mootha and his colleagues then used publicly available expression profile data--data from DNA chips that allows researchers to study which of thousands of genes are on or off in any given cell. Such expression profiles generate signature patterns that are unique to cell types. The researchers screened the profiles to see which of the genes of unknown function had the expression signature, or DNA fingerprint, of a mitochondrial gene. In less than one week, they found one gene, LRPPRC, that had a striking signature of a mitochondrial gene. They then studied mouse data, and the same gene popped up again.
In the meantime, the Montreal Genome Centre in McGill University was also working on the genome sequences. Pierre LePage, working in Hudson's laboratory independently identified the same gene, corroborating the suspicion that LRPPRC was indeed the responsible gene.
"We were really excited, but wanted more experimental proof that this was indeed the culprit," says Mootha, who was collaborating with MDS Proteomics in Denmark to compile a comprehensive list of all proteins in mitochondria, using mass spectrometry. The COX team then studied to see if any of the DNA sequences in the region on chromosome 2 was associated with a protein from this dataset of mitochondrial proteins. They found that the LRPPRC gene made the list.
For final clinical proo
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Contact: Christine Zeindler
christine.zeindler@muhc.mcgill.ca
514-934-1934
McGill University
14-Jan-2003