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Folic acid deficiency has multigenerational effects
Date:9/27/2013

thereby causing developmental problems.

Dr. Roy Gravel, also a co-author of the study and member of the Alberta Childrens' Hospital Research Institute says this study provides a tremendous opportunity to look at the prevention of diseases like spina bifida. "The work began as a study of a gene called Mtrr in mice. The goal was to shed light on how a mutation in Mtrr would affect folate metabolism. The multigeneral effect we observed was completely unexpected," says Gravel.

The Mtrr gene encodes an enzyme that is key to the metabolism of folic acid and, when mutated, causes similar effects to dietary folic acid deficiency. The researchers found that when either the maternal grandmother or the maternal grandfather had this Mtrr mutation, their genetically normal grandchildren were at risk of a wide spectrum of developmental abnormalities, even if the mutated gene was not inherited through to the next generations.

These developmental abnormalities were also seen in the fourth and fifth generations of mice.

Through a series of experiments, researchers discovered that the developmental abnormalities were not passed down genetically. Instead, the defects were the result of "epigenetic" changes, which had been inherited. Epigenetics is a process which turns genes on and off through chemical modifications to DNA without changing the genetic code itself. Epigenetic inheritance refers to the passing along of these epigenetic marks as cells divide during development. It had been previously thought that epigenetic modifications were, for the most part, 'wiped clean' after each generation.

The researchers hypothesize that, for a yet unknown reason, some of these abnormal epigenetic marks caused by the Mtrr mutation escape this normal erasure and are inherited by the next generation. If the abnormal epigenetic marks that regulate genes important for development are inherited, then these generations may develop abnormalities as a result of the wrong genes bein
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Contact: Gloria Visser-Niven
gvissern@ucalgary.ca
403-210-6615
University of Calgary
Source:Eurekalert

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