Tuesday, September 4, 2007

Genome Study Shines Light On Genetic Link To Height

Finding: Inheriting the 'C'-containing copy of the HMGA2 gene -- a 'C' written in the DNA code instead of a 'T' often makes people taller: one copy can add about a half centimeter in height while two copies can add almost a full centimeter.

Why do tall people get to be tall?
Nearly a century ago it was thought that many genes likely influence how tall a person grows, but little progress was made to find the genes, until now.

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 compared to shorter individuals. By analyzing DNA from nearly 35,000 people, the researchers zeroed in on a difference in the HMGA2 gene -- a 'C' written in the DNA code instead of a 'T'. This gene change can account for the difference in tallnes.

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

In addition to being a textbook example of a complex trait, height is a common reason children are referred to medical specialists. Although short stature by itself typically does not signal cause for concern, delayed growth can sometimes reflect a serious underlying health condition.

DNA accounts for 90% of growth
Nearly 90% 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. Although a few genes have been uncovered through studies of rare, single-gene stature disorders, most do not seem to be associated with height in the general population. Recent advances, including the completion of the HapMap project and the availability of large-scale research tools, enabled the scientists to take a systematic approach to understand how common genetic differences can impact a person's height.

After scrutinizing the initial data, the scientists identified a single letter change -- known as a single nucleotide polymorphism or SNP -- in the HMGA2 gene as the most promising result. They collaborated with additional researchers to study this SNP through a second phase of analysis that encompassed nearly 30,000 individuals: adults and children from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Exeter Family Study of Childhood Health (EFSOCH),

Unlike most other complex traits, height is something that can be easily defined and measured in very large numbers of people. Soon the scientific community will have access to many more large-scale genomic data sets, making it feasible to identify additional genes involved in height."

What the Gene does
While surprisingly little is known about how genes hardwire humans for growth, some initial clues have already surfaced as a result of the HMGA2 discovery. The gene is active in the first months of fetal growth and shuts off shortly before birth, suggesting it orchestrates growth-related events early in human development. Moreover, it appears to influence the overall longitudinal growth of the skeleton, as scientists found that the T-to-C change in the gene's DNA sequence correlates with an increased length of both the limbs and spine in young children. HMGA2 has also been implicated in certain forms of cancer. Thus, further studies may help dissect the relationship between normal growth and the deranged growth central to cancer.

No comments: