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Identification of genes causing defects in vitamin B12 metabolism

Montreal, December 10, 2002 Investigators at the University of Calgary and McGill University have identified genes that underlie two severe diseases of vitamin B12 metabolism. The two diseases, known as the cblA and cblB forms of methylmalonic aciduria, may produce brain damage, mental retardation and even death if not detected in infancy or early childhood.

Melissa Dobson, a graduate student at the University of Calgary working with Roy Gravel PhD in the Department of Biochemistry and Molecular Biology, is lead author of two papers reporting the identification of the two genes. The genes were first identified in bacteria and then traced to their human counterparts. She credits the human genome project with her breakthrough. "We can now compare human and bacterial DNA sequences to find human genes," states Dobson. "This was made possible by the availability of the sequence of the complete human genome."

To prove whether she and colleague Daniel Leclerc, PhD, had identified the correct genes, she approached her McGill collaborators, Dr. David Rosenblatt and Dr. Thomas Hudson, for help in screening patients. The McGill University Health Centre (MUHC) has a world-renowned diagnostic facility and cell bank for patients with genetic diseases involving vitamin B12. Using Genome Quebec's MUHC -based sequencing centre, Dobson and her colleagues confirmed the presence of mutations in DNA from patients with the two diseases.

"We have identified two different genes that are critical to the processing of vitamin B12 by finding mutations in patients who have particular forms of methylmalonic aciduria," according to Dobson. Methylmalonic acid is a chemical intermediate in the breakdown of proteins and other substances. It accumulates in the body and is excreted in large amounts in the urine because the blocks in the processing of vitamin B12 prevent its metabolism.

Identifying the genes that cause cblA and cblB represents a landmark breakthro
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Contact: Christine Zeindler
christine.zeindler@muhc.mcgill.ca
514-934-1934
McGill University
10-Dec-2002


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