Monday, July 02, 2007

Why Does Increasing Paternal Age Lead to More Children With Type 1 Diabetes?

T h e B o s t o n G l o b e M o n d a y , M a y 2 1 , 2 0 0 7

By Catherine Elton

Medical research is undergoing a
sea change in its approach to
linking genes to disease. Instead
of hunting individual mutant
genes — a painstaking, expensive
process — researchers are more
often turning to a bold, computer-
driven technique that allows for fast, cheap scanning
of vast regions of DNA for anomalies that can
make people more susceptible to a disease or even directly
trigger illness. It’s not a diagnostic tool yet, but
so-called ‘‘genome-wide association’’ research has over
the past months produced dramatic results linking
hitherto unexplored patches of genetic terrain with
such common killers as heart disease and diabetes.
‘‘We used to hold a single lamp’’ over a suspicious
gene, said Dr. Francis S. Collins, director of the National
Human Genome Research Institute. ‘‘Now
we’re able to light a whole street and survey the entire
The discoveries are the fruit of two huge projects
completed in this decade, the mapping of the human
genome — which showed just how similar human beings
are, with each of us carrying DNA that is 99.9
percent identical — and, just as significant, the mapping
of human genetic variation, completed in 2005.
The regions of variation, although small relative to
the rest of the genome, carry 10 million snippets of
genetic material that vary from individual to individual.
These sections, known as single nucleotide polymorphisms,
or SNPs (pronounced ‘‘snips’’), cause
such happy traits as green eyes or red hair. But they
also are lairs for disease.
In a discovery announced last month by the Broad
Institute of Harvard and MIT, researchers used SNPs
technology to identify genetic variations linked to the
most common form of diabetes. That was a major advance
in uncovering the genetic origins of disease because
the defects occurred in areas of ‘‘junk DNA’’
long dismissed as meaningless, according to Dr. David
Altshuler, professor of medicine at Harvard and
leader of the Broad research team.
The discoveries were possible only because of a
powerful technique that uses thumbnail-sized ‘‘chips’’
smeared with DNA. Each chip can carry up to half a
million SNPs, allowing researchers to scan huge
swaths of an individual’s DNA in seconds, at small
cost. Scan results, in turn, can be quickly compared
with SNP chips containing genetic material from tens
of thousands of other individuals.
So, by comparing DNA from thousands of people
with heart disease or diabetes, say, with DNA from
healthy individuals, researchers can rapidly discover
genetic variances common to those with the disease
and absent from those with no illness.



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