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Gene Shortage Might Lead to Shorter Height, Study Says
Date:11/23/2011

By Maureen Salamon
HealthDay Reporter

WEDNESDAY, Nov. 23 (HealthDay News) -- Tall or short, it's long been known that genes account for much of a person's height. Now, scientists have found that short people actually might be missing copies of certain genes, which can leave them significantly smaller than average.

Studying DNA from more than 11,000 children and adults, an international team of researchers learned that those of short stature -- defined roughly as falling into the shortest 2.5 percent of their peer group -- had an excess number of rare deletions, or missing copies, of specific genes. Thus far, most research into genes and height has centered on identifying variations in common genes instead of an absence of others, study author Dr. Joel Hirschhorn said.

"We were a little bit surprised, since we didn't really know what we would find going in [to the study] and whether we would see enough of an effect," said Hirschhorn, a professor of genetics at Children's Hospital Boston. "We were trying to figure out what's the underlying genetics of height and things like it, and this is a class of variation less well studied."

The study is published in the December issue of the American Journal of Human Genetics.

Common gene variants linked to height explain only about 10 percent of the variation in adult height, Hirschhorn said, but perhaps half of such variation might eventually be explained by some of the differences his team studied.

First analyzing the DNA of more than 4,400 children whose genetic material was collected for other purposes, the researchers observed that many more CNVs or "copy-number variants" -- in this case, fewer copies of a gene -- were present in those of short stature.

Extending the findings to a larger, population-based group of nearly 6,900 African Americans, the scientists again found that shorter participants had an excess of such missing gene copies. These deletions would typically be inherited from one's parents, but not always, Hirschhorn said.

"Usually [researchers] look at variants one at a time, but this is a cumulative-effect type of variation," said Hirschhorn, also a senior associate at the Broad Institute, a biomedical research organization in Cambridge, Mass.

Several limitations might affect the validity of the study results, the authors acknowledged. One is the fact that children whose DNA was evaluated had initially undergone genetic analysis for other reasons such as developmental delays, autism spectrum disorders and multiple birth defects. So it's possible that those with many missing gene copies are likelier to have conditions leading to poor growth, the study said, but the replication of results in a more representative population suggests the findings can be generalized to others.

More information

Stanford University School of Medicine has more about inherited traits.

SOURCES: Joel N. Hirschhorn, M.D., Ph.D., professor of genetics, Children's Hospital Boston, senior associate, Broad Institute, Cambridge, Mass.; December 2011, American Journal of Human Genetics


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