The size difference between towering basketball star Shaquille O'Neal and diminutive horse jockey Jorge Chavez is predominantly due to differences in their genes--but which genes has been a mystery. Now three teams have made a major leap, identifying dozens of genes and regions of our DNA that influence height. The find could lead to a better understanding of growth disorders and other diseases, such as cancer.
Height is an inherited trait, so variations in genes should explain why some people are tall and some are short. But other than rare mutations that result in dwarfism or gigantism, scientists have had little success identifying genes that govern stature. A strategy called genome-wide association is changing the tide: By rapidly scanning a sample of a person's entire genome for variations in DNA associated with common disorders, researchers have found novel genes behind diabetes and heart disease (ScienceNOW, 3 May 2007). The strategy has also previously identified the first two DNA regions linked to normal height differences, and now three teams have added dozens more.
In separate efforts, each team pooled genetic and height data collected from other studies to amass information on 13,000 to 31,000 people. The teams then scanned their respective databases for single-nucleotide polymorphisms--regions where the DNA differs by one base--that were associated with being either taller or shorter than average. Researchers led by Kári Stefánsson, a geneticist with deCODE Genetics in Reykjavik, Iceland, identified 27 such regions, and the other two groups, led by geneticist Timothy Frayling at Peninsula Medical School in Exeter in the U.K., and Joel Hirschhorn, a geneticist at the Broad Institute in Cambridge, Massachusetts, spotted 20 and 10 regions, respectively. (The teams have not yet had a chance to compare their findings, so it's not yet clear how much overlap there is.) People who carried mostly "tall" versions of these genetic variations were 3.5 to 5 cm taller on average than people carrying mostly short versions, the teams report online this week in three papers in Nature Genetics.
The researchers don't yet know how these genetic variations influence height. Some occur in genes that play a role in skeletal growth and development, which makes sense, but others lie in genes that trigger cancer or in undeciphered regions of DNA. What's more, the genetic variations account for less than 4% of the height variation found in the general population, so the researchers think numerous more regions remain to be identified.
The genome-wide association strategy may not be the best approach for identifying these remaining variations, says Justine Ellis, a geneticist at the University of Melbourne in Australia. She notes that the approach could overlook genes that affect height only when triggered by certain circumstances, such as a poor diet. Geneticist Peter Visscher of Queensland Institute of Medical Research in Brisbane, Australia, thinks that as researchers discover more variations linked to height they may one day be used to analyze DNA left at the scene of a crime to determine the height of a suspect.