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Copper research shows pregnancy nutrigenomics promise

By staff reporter , 09-Aug-2006

Researchers investigating the interplay between nutrition, genetic variation and birth defects have reported their first positive results on copper metabolism, stoking hopes that their approach may eventually enable every expectant mother to receive tailored nutritional advice.

Women receive abundant advice on diet during pregnancy, which seems to change regularly and vary from country to country. Researchers from the University of Washington have sought to push research beyond whether or not soft cheese should be avoided and how much fish to eat each week, to determine how the lack of a specific nutrient interacts with the genetics of a developing embryo.

"We already know that nutrition is a critical issue in birth defects and that folic acid is an essential supplement in some women for the prevention of spina bifida in the developing foetus," said Jonathan Gitlin, MD, who oversaw the work of MD/PhD student Bryce Mendelsohn. "The ultimate goal of this research is to bring the power of genomic medicine to every woman."

The team's first experiments, reported in the August issue of Cell Metabolism (doi:10.1016/j.cmet.2006.05.001), used a chemical genetic screen to identify small molecules that affect copper levels and metabolism in the zebrafish, and how abnormal metabolism affected development of the fish's notochord (spinal column).

Zebrafish are often used in early stage genetic research since, not only is their development similar to that of humans, the embryos are transparent and grow outside the mothers' bodies.

But Mendelsohn's findings indicate that no matter how much copper a zebrafish embryo has, variants in the gene responsible for copper metabolism, known as atp7a, prevent it from functioning properly. This leads to abnormal copper metabolism and impaired development of the notocord.

In humans, abnormal copper metabolism caused by mutation in the equivalent of the atp7a gene causes a rare but fatal hereditary disease called Menkes disease.

The researchers believe that the zebrafish model may not only pave the way for the development of novel therepeutics for Menkes diseaes, but also to greater understanding of the role of copper in other birth defects such as curvature of the spine.

Human food sources of copper include shellfish, nuts and liver, and the trace metal plays an important role in maintaining iron levels, the formation of connective tissue, brain nerve cell function, hormone production and pigmentation.

The Washington University team is already looking beyond copper, adapting the same methods to identify other genes involved in the metabolism of other nutrients.

"The knowledge of genetic variations serves as a unique, individual guide for providing the essential nutritional intake that will ensure a normal, healthy infant," said Gitlin.

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