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Published online 5 November 2008 | Nature 456, 18-21 (2008) | doi:10.1038/456018a
News Feature
Personal genomes: The case of the missing heritability
When scientists opened up the human genome, they expected to find the genetic components of common traits and diseases. But they were nowhere to be seen. Brendan Maher shines a light on six places where the missing loot could be stashed away.
If you want to predict how tall your children might one day be, a good bet would be to look in the mirror, and at your mate. Studies going back almost a century have estimated that height is 80–90% heritable.
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Deep resequencing of positional candidate genes (coding as well as non-coding parts) may be valuable. These candidate genes should be selected in a rigorous manner. A systems approach encompassing transcriptome, proteome and lietarture mining, for example, may help select promising candidates in linkage and/or association regions. In brief, a system-wide sequencing startegy may prove valuable.
The idea that the investigator has "controlled" for environment in twin or sibling studies is mythology. Environmental factors are complex, variable, interactive and dynamic--even more so than the genome.
"Studies going back almost a century have estimated that height is 80?90% heritable. So if 29 centimetres separate the tallest 5% of a population from the shortest, then genetics would account for as many as 27 of them." This should say height is 80-90% heritable...with all other factors being equal. Genetics doesn't explain anything close to 27 centimeters of the short/tall gap, given variability in diet, disease, and other environmental factors that influence metabolism (and can never be adequately controlled for). The increase in mean height between my generation and that of my grandparents is almost certainly 0% genetic. And you'd be hard pressed to find a biologist under 40 who has ever been "surprised" by pleiotropism.
One key concern this article raises is that NIH and NSF have pushed relentlessly toward unproven science that concentrates resources in the hands of a few universities and business enterprises. If this research tack doesn't pan out we have wasted billions of dollars on a shift toward "big science" while literally thousands of new, young, small labs never had a chance to get going. I am happy to see Nature at least raise a few critical points; but to me this highlights the need for more honest, open and critical discussions about the course of science. NIH's hounding of critics under Zerhouni (Andy Marks' sincere comments really needed to be replied to by all 28 NIH institute heads? yikes..)and dictatorial/"Bushian" decision making processes have set science back in the U.S. I hope we can do better in future.