Science and sensibility

Quantitative traits like height are usually the result of several genes interacting to produce one phenotype, changing one gene usually only slightly alters the end result but all the genes that effect height combined with environmental effects provide enough variation to make Yao Ming and Danny DeVito. It had proved very difficult for geneticist to untangle the effect of individual genes in the milieu of genes an environment that make up these complex traits. Recently a team of Dutch scientists have completed a scan of the entire genome of a number of siblings in an attempt to do some untangling and isolate areas of the genome that contribute to height in humans.

It can prove difficult to map genes for quantitative traits onto chromosomes so instead something called a quantitative traits locus (QTL) is used. A QTL can be defined as area of the genome containing a gene that contributes to a phenotype being studied. In this study the researchers scanned the genomes of siblings not for known genes but for markers that the human genome project has set out more or less evenly spaced across the genome. By the wonders (and mysteries) of modern statistics the team could show which of these markers is associated with differences in height amongst the siblings. That is not to say that the markers themselves (which are very short stretches of DNA indeed) are causing the variation, rather the markers are close enough to genes that effect height that they aren’t often split up during crossing over as part of meiosis. With the whole genome scanned each marker can be can be assigned something called a LOD (log of the odds) score which is a measure of the probability that that marker is linked with a gene effecting that trait. A LOD score of 2 means that it is one hundred times more likely to be linked to such a gene than not. The results of the whole genome scan are summarised in the graph below.

The strongest linkage for any marker was found on chromosome 6, a number of similar studies have found similar results strongly suggesting there is something in this region influencing height. Further support to that claim comes from the fact that area of the genome contains the oestrogen receptor alpha gene, which has been suggested to effect height. An area on chromosome 18 with a high LOD score also correlates to other studies, all told the Dutch team found a total of seven areas in the genome that might effect height. If these QTLs are supported by other studies then scientists can start looking at sequence of these areas provided by the Human Genome Project and start determining which individual genes are playing major roles in influencing one of the more complex of human traits.

(Willemsen et al (2004), QTLs for height: results of a full genome scan in Dutch sibling pairs, European Journal of Human Genetics, 820-8)