TALL STORY Tiny gene variation influences height
By Richard Ingham, Agence France-Presse
PARIS Scientists have uncovered the first gene that helps explain common differences in height among humans. Just a single change in the gene's dna code determines whether people will be taller or shorter by up to one centimeter, they said, adding that hundreds of other genes are also likely to play a role in height. Genetic heritage has long been known as the driver of height-everyone knows that a child whose parents are both tall is also likely to grow up tall. Unlike obesity, where genes and environmental factors (nutrition and exercise, for example) play a joint role, around 90 percent of the determinants for height are genetic. Even though the link is clearly there, finding "height" genes that are common across the population has been strangely elusive. Until now, the only evidence has been spotted among a small group of people with a rare condition that affects their stature. In a paper published by Nature Genetics, British and US researchers analyzed dna from nearly 5,000 white people of European descent, mainly individuals living in Britain, Sweden, and Finland. The exhaustive trawl threw up a gene called hmga2. The change of just a single base "letter" in hmga2's genetic code-a "C" (for cytosine) instead of a "T" (for thymine)-adds nearly a centimeter in height to individuals who inherited this variant from both parents. Those who got the "C" variant from only one of their parents were about half a centimeter taller than their "T" counterparts. After comparing this discovery with further studies of nearly 30,000 other people, the team believes around a quarter of white Europeans carry the double "C" variant. Around a quarter have the double "T" version, thus leaving them about a centimeter shorter than their double "C" counterparts. Many more other genes remain to be uncovered, for hmga2 explains only 0.3 percent of the variability in human stature. "Height is a typical 'polygenic' trait, in other words many genes contribute towards making us taller or shorter," said lead researcher Tim Frayling of the Peninsula Medical School in Exeter, southwestern England. "Clearly, our results do not explain why one person will be six feet, five inches, and another only four feet, 10 inches. This is just the first of many that will be found, possibly as many as several hundred." Another step is to explain why hmga2 has this effect. Researchers believe it plays a role in growth through regulating cell growth. Interest in "height" genes is spurred by more than idle curiosity, for there could also be a windfall in knowledge about disease. Taller people are statistically more likely to be at risk from some kinds of cancer (prostate, bladder, and lung, for instance), which implies that genes that regulate cell multiplication may also play some part in letting cancer cells proliferate. Statistics also throw up an association between shortness and heart disease. "This is the first convincing result that explains how dna can affect normal variation in human height," said US researcher Joel Hirschhorn of the Broad Institute, Massachusetts, and a professor of genetics at Harvard Medical School. "Because height is a complex trait, involving a variety of genetic and nongenetic factors, it can teach us valuable lessons about the genetic framework of other complex traits, such as diabetes, cancer, and other common human diseases." M
Marlowe Hood, Agence France-Presse
PARIS The first individual genome ever sequenced-a complete dna blueprint of celebrity scientist Craig Venter-has revealed genetic variation among humans far richer than previously imagined. Published in the online open-access journal PLoS Biology, the 2.8 billion contiguous bits of genetic code will also hasten advances in preventive medicine, said Venter, who is both an author and the object of the study. Within five years, faster and cheaper sequencing techniques could produce complete genomes for 10,000 people, laying the foundation for "an era of individualized genomics," he predicted. "Once we have those, we will basically be able to sort out every fundamental question about nature versus nurture, what's genetic and what's environment," he said. The findings overturn what had in a few short years become genetic gospel: that all human beings are, genetically speaking, 99.9 identical. Venter himself trumpeted this idea in 2000 when his biotech firm Celera, which he left in 2003, and a team of US-government scientists simultaneously unveiled-after a bruising race to the finish line-the first complete human genome. Both of these earlier efforts were flawed and greatly underestimated genetic diversity, he and his colleagues now say, because the whole had been assembled from a hodgepodge of dna taken from several individuals. The variations revealed in the new genome, dubbed "HuRef," go far beyond previously identified single-nucleotide polymorphisms (snps), once thought to be the key to differences in human traits and disease susceptibility. Snps are dna sequence variations that occur when a single nucleotide-the basic building blocks, composed in pairs, of dna-in the genome sequence is altered. Also important, however, are previously overlooked variations in stretches of genetic code that were once dismissed as useless "junk dna." "This dispels the notion we had in 2000 and 2001 that we all have exactly the same genes in the human population," said Venter. "It would have been very disturbing if the range of characteristics that we see all came down to a few simple snp variations." The new data show that in an individual genome upwards of 44 percent of genes are variable in sequence. "This is a number that geneticists and biologists have been wondering about for 50 to 100 years," commented coauthor Stephen Scherer, a geneticist at The Hospital for Sick Children in Toronto. "HuRef" was built on the foundation of Venter's earlier project, which was already 60 percent composed of his own dna. But it still took an additional US$10 million and three years to complete. To spur more efficient technologies, Venter has contributed US$500,000 dollars to the US$10 million Archon X Prize for scientists who come up with genome-sequencing techniques that are rapid, accurate, and inexpensive. Some ethicists have expressed concerns about the possible abuse of personal health information that may be easily accessible once coding individual genomes becomes routine. The study itself raises the issue, if only indirectly: a table listing some of the traits commonly associated with certain gene expressions found in Venter's genome reveals more than some people might care to. A genetic propensity toward Alzheimer's and cardiovascular disease, for example, prompted Venter to take statins, a compound thought to help forestall both conditions. But that same information-or the fact that one tends toward tobacco addiction or alcoholism, other traits identified in the study-could be seen in another light by potential insurers or employers, critics point out. For Venter, the possible advantages far outweigh such concerns. "We have all been taught that we should fear this information. We hope to teach people they should welcome it as a breath of fresh air that gives them opportunities in their lives." He did, however, allow for the possibility that anybody's genome information "is relatively easy to get." Other researchers who worked on the three-year project at Venter's eponymous institute came from the University of Barcelona and the University of California at San Diego. M |
