AMHERST, Mass. Though the human genome has been sequenced, scientists are still trying to figure out how the accomplishment can help people, for example, how it can be used to treat disease. As University of Massachusetts Amherst geneticist Jacob Mayfield notes, "It was easy to think of the human genome as the big prize, but what we realize now is, it's just a foot in the door."
"What we're beginning to understand is that the information we're interested in knowing lies in comparisons between genomes," he adds. As society moves to personalized, genome-based medicine, "much work remains for us to grasp what it is that we know. As we uncover new variations at the DNA level, we have to address their consequences. To learn what genetic differences mean to the whole organism, we have to find ways of asking about function. Because the way genes interact to cause traits like red hair isn't understood, let alone how they cause disease!"
To tackle this and make a difference in a human disease, he and colleagues at the University of California Berkeley devised a technique for testing the consequence of variant human gene alleles (alternative sequences of a single gene) by moving them into yeast cells. Once swapped into yeast, colony growth can be compared to reveal functional differences. The technique is reported in the current issue of Genetics.
For this study Mayfield's team first used DNA sequence databases to select variant gene sequences that tested positive for the metabolic disease homocystinuria, which can cause a range of mild to severe symptoms such as blood clots, mental retardation and other problems. Deficiencies in a gene called Cystathionine-beta-synthase (CBS) are often the cause. Because early intervention for homocystinuria can eliminate severe symptoms, newborn screening began in the 1970s.
The researchers selected CBS gene sequences from 84 patients and made a piece of recombinant DNA that matched the
|Contact: Janet Lathrop|
University of Massachusetts at Amherst