It became clear nearly a century ago that a number of genes likely influence how tall a person grows, though little progress, if any, has followed in defining the myriad genes. Now an international research team brings light to this age-old question by pinpointing a genetic variant linked to human height -- the first consistent genetic link to be reported.

The findings, reported in the September 2 advance online edition of Nature Genetics, stem from a large-scale effort led by researchers at the Broad Institute of MIT and Harvard, Children's Hospital Boston, the University of Oxford and Peninsula Medical School, Exeter.

In addition to being a textbook example of a complex trait, height is a common reason children are referred to medical specialists. Eventhough short stature by itself typically does not signal cause for concern, delayed growth can sometimes reflect a serious underlying health condition. "By defining the genes that normally affect stature, we might someday be able to better reassure parents that their child's height is within the range predicted by DNA, rather than a consequence of disease," said co-senior author Joel Hirschhorn, an associate member of the Broad Institute also affiliated with Children's Hospital Boston and Harvard Medical School.

Using a new "genome-wide association" method, the research team searched the human genome for single-letter differences in the genetic code that appear more often in tall individuals in comparison to shorter individuals. By analyzing DNA from nearly 35,000 people, the scientists zeroed in on a difference in the HMGA2 gene -- a 'C' written in the DNA code instead of a 'T'. Inheriting the 'C'-containing copy of the gene often makes people taller: one copy can add about a half centimeter in height while two copies can add almost a full centimeter.

"This is the first convincing result that explains how DNA can affect normal variation in human height," said Hirschhorn. "Because height is a complex trait, involving a variety of genetic and non-genetic factors, it can teach us valuable lessons about the genetic framework of other complex traits -- such as diabetes, cancer and other common human diseases".

Nearly 90 percent of the variation in height among most human populations can be attributed to DNA. The remainder is due to environmental and lifestyle factors, such as nutrition. Eventhough a few genes have been uncovered through studies of rare, single-gene stature disorders, most do not seem to be linked to height in the general population. Recent advances, including the completion of the HapMap project and the availability of large-scale research tools, enabled the researchers to take a systematic approach to understand how common genetic differences can impact a person's height.


Posted by: Emily    Source

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