<http://www.sciencedaily.com/releases/2008/03/080326124806.htm>

New Genetic Markers For Crohn's Disease Discovered, Study Suggests

ScienceDaily (Mar. 27, 2008) — What is believed to be the largest study of
its kind for the genetic roots of inflammatory bowel diseases has
suggested new links to Crohn's Disease as well as further evidence that
some people of Jewish descent are more likely to develop it.

The study examined changes in DNA associated with the two most common
forms of inflammatory bowel disease (IBD): Crohn's Disease (CD), which is
most frequently marked by inflammation of the final section of the small
bowel (ileum) and parts of the colon, and ulcerative colitis (UC), an
inflammation of the internal lining of the rectum and colon.

Results of the study, published in this month's edition of Genes and
Immunity, included information gleaned from 993 families with IBD, 244 of
whom were Ashkenazi Jews. Up to 30 percent of people with IBD in the
United States are estimated to have a family history of the condition, and
about 25 percent of these families have both CD and UC in the family.
People of Ashkenazi Jewish descent are at least twice as likely to develop
a form of IBD and are more likely to have familial disease.

"This increased risk for some Jewish people makes our study and results
especially significant since this is the first sample size of Jewish
families, 244, that was large enough to identify novel gene regions for
familial predisposition in this ethnic group," says Johns Hopkins
gastroenterologist and genetic investigator Steven R. Brant, M.D., senior
author of the study.

By analyzing common DNA variations known as single nucleotide
polymorphisms, or SNPs, the team found evidence for genes causing familial
Crohn's Disease in the study population specific to Ashkenazi Jewish
families with CD on previously identified areas of chromosomes 1 and 3.
They also identified a never-before-identified region of chromosome 13
that was shared by both Jewish and non-Jewish families with CD. Evidence
for chromosomal regions that may be linked to UC on chromosome 2 and 19
for Jewish and non-Jewish families was also noted, according to Brant.

"What makes these results especially significant is not only the large
sample size but also the method we used for screening, namely the use of a
high-density, single-nucleotide polymorphism genome-wide linkage process,
says Brant." The new process is 10 times faster than older methods at
searching the number of variations across the genome, he added.

Up to now, Brant says, no gene regions implicated in IBD were specific to
Ashkenazi families, and genetic evidence pointing to why Ashkenazi Jews
are twice as likely to get the disorder was lacking. The two genetic
regions identified on chromosomes 1 and 3 were specific to Ashkenazi CD
and unrelated to known IBD genes.

Although further study is needed to narrow down which specific genes are
the major players, Brant says it's already clear that they are in the
right "neighborhood" to search for IBD/CD susceptibility genes.

The National Institute of Diabetes and Digestive and Kidney Diseases
Inflammatory Bowel Diseases Genetics Consortium (NIDDK-IBDGC) that
organized the study is a multi-center team of American and Canadian
investigators established in 2002 to examine genetic links among IBD
pedigrees.

The subjects were recruited through the six IBD genetic research centers
of the NIDDK-IBDGC -- Cedars-Sinai Hospital in Los Angeles, Johns Hopkins
Hospital, the University of Chicago, the University of Montreal, the
University of Pittsburgh and the University of Toronto.

Genotyping was performed at the SNP Center at the Center for Inherited
Disease Research, Baltimore, Md.

The study was funded by the NIDDK, branch of the National Institutes of
Health (NIH). Other researchers who worked on this study include lead
author Yin Shugart, Ph.D., Johns Hopkins Bloomberg School of Public
Health; co-senior author Judy H. Cho, M.D., Yale University School of
Medicine, New Haven, Conn. and additional researchers from University of
Toronto, Toronto, Canada; University of Pittsburgh, Pittsburgh;
Cedar-Sinai Medical Center, Los Angeles; Johns Hopkins University,
Baltimore; University of Chicago, Chicago; University of Manitoba,
Winnipeg, Manitoba, Canada; University of Sherbrooke Hospital, Fleurimont,
Quebec, Canada; McGill University, Montreal, Quebec, Canada and University
of Montreal, Quebec, Canada.