Scientists at Ben-Gurion University of the Negev in Beersheba have identified a mutant gene that causes congenital intestinal blockages – extreme constipation – in infants born to members of two different Beduin tribes.

Prof. Ohad Birk and colleagues at BGU and Soroka University Medical Center, who discovered mutations in the GUCY2C gene, reported it in the new edition of the prestigious American Journal of Human Genetics.

The discovery, Birk told The Jerusalem Post on Sunday, could help couples with one of the mutations to have healthy children through pre-implantation genetic diagnosis and eventually lead to better understanding of cystic fibrosis (CF) in the general population.

The gene mutations developed in Beduin in the Negev and not in the Galilee some 400 years ago, he added.

“It was very odd that people shared the same mutation, but some were born with severe intestinal obstruction and some not. Some claim that there is a ‘modifier gene’ that influences the outcome,” he said.

There are apparently only dozens of carriers among Beduin in the Negev, thus it is not common. But some children with the disease have undergone serious operations in which large parts of the intestines had to be removed.

Intestinal obstructions have many causes, some of which are genetic. In extreme cases, such as in some instances of the genetic disease cystic fibrosis, intestinal blockages are found even at birth.

Mutations in GUCY2C that cancel out its function were identified in two different tribes in the Negev among whom conganguinity (inbreeding) is common and increases the prevalence of genetic diseases.

In the new mutations, there were cases of intestinal obstructions (meconeum ileus) in newborns without any evidence of CF. The GUCY2C gene, known to activate the gene for CF, expresses solely in the intestine.

Therefore, mutations that impair its function inactivate the functioning of the gene for CF only in the intestine, causing obstructions in newborns without any of the other effects of CF.

Mutations in the GUCY2C gene might serve to protect against diarrheal infections such as E. coli. Unlike normal laboratory mice that die of severe diarrhea when infected with E. coli bacteria, mice with a GUCY2C mutation do not. Apparently, the mutation might have evolved in the Beduin to protect them from diarrheal diseases and the loss of fluids in their harsh desert surroundings.

Interestingly, a publication by another research group at the same time has shown that a different mutation in the same gene causes an opposite effect, increasing its activity and leading to diarrhea in newborns. Thus, different mutations in the same gene apparently govern the tendency towards intestinal obstruction or diarrhea in extreme cases, Birk said.

Birk, who is head of Soroka’s genetics institute and of BGU’s Morris Kahn Laboratory of Human Genetics, and his colleagues, are continuing the research to determine whether more subtle changes in this gene control the tendency to diarrhea or constipation in the population at large.

The article emerged from the doctoral research of Dr. Hila Romi in Birk’s research group. So far, Birk’s research team has discovered the genetic mutations leading to more than 20 human diseases.

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