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Newly discovered height gene has disease link

By Steve Connor

Scientists believe they have uncovered the genetic link to height – explaining for the first time why some children are smaller than their friends.

The slightest genetic mutation can knock a centimetre off a child's eventual height, according to a study analysing the DNA of nearly 5,000 people.

The discovery means that it may soon be possible to reassure the anxious parents of unusually short children or explain why tall people run a greater risk of certain diseases such as cancers of the bladder, prostate and lungs.

Height varies widely in men and women but in modern, western societies the variation between people is almost entirely due to genes because important environmental factors, such as diet, tend to be uniform enough not to affect the overall growth of the bones. Finding any of the many different genetic factors that influence height has proved to be difficult. Large-scale genetic studies set up in the wake of the human genome project have now allowed a detailed investigation at the level of mutations within the DNA molecule.

The latest study, published in the journal Nature Genetics, has identified a single switch in just one letter of the genetic code in a gene called HMGA2. People who inherit both changes can be a centimetre (a third of an inch) shorter than those who inherit both of the alternative versions of the gene.

One of the study's leaders, Dr Tim Frayling of the Peninsula Medical School in Exeter, said that everyone carries two copies of the HMGA2 gene and that about 25 per cent of white Europeans will carry both versions of the "tall" gene and another 25 per cent will carry both versions of the "short" gene.

He said: "Height is a typical 'polygenic' trait. In other words many genes contribute towards making us taller or shorter. Clearly our results do not explain why one person will be 6ft 5ins and another only 4ft 10ins. This is just the first of many – possibly as many as several hundred – that will be found. Even though improved nutrition means that each generation is getting successively taller, variation in height within a population is almost entirely influenced by our genes."

There seems to be a definite link between height and the risk of developing certain diseases, according to Mike Weedon also of the Peninsula Medical School.

He said: "For example, there are associations between shortness and slightly increased risks of conditions such as heart disease. Similarly, tall people are more at risk from certain cancers and possibly osteoporosis."

The scientists believe one possibility is that the "tallness" mutation in the HMGA2 gene affects cell division within the body, which may influence the probability of developing cancer in some people.

Other team leaders were Professor Mark McCarthy of Oxford University and Dr Joel Hirschhorn, a geneticist at Harvard Medical School.

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