There’s no such thing as the human genome. Every person’s genome is unique (even identical twins aren’t really identical genetically). So, it’s no surprise that each of us carries a unique combination of alleles and mutations. And, so new study shows, we all carry a unique set of flaws in our genes.
46 chromosomes making up the genome of a human male. (Wikimedia Commons, National Human Genome Research Institute)
The study took a look at the genomes of 179 people who participated in the 1000 Genomes Project and put their sequenced genomes next to a database of known disease-causing genetic variants. Due to annotation errors and unknown functions of genes, exact numbers are, of course, hard to determine. However, the current best estimates of the authors suggest that each of us provides a home for roughly 400 damaging gene variants and about 2 genuine disease mutations (For more information, check the open access article, reference below).
Then why aren’t we all diseased (for the moment neglecting the issue that health and disease aren’t necessarily part of a clear dichotomy)? Well, there probably are a number of reason for that.
First, ‘one gene one function’, and the reverse ‘one function one gene’, rarely holds. It’s more like ‘many genes many functions’ and its reverse. One gene often influences many functions, and one function is, in the majority of cases, influenced by many genes. It’s an astoundingly complex network. The failure, or bad influence, of one gene can thus be potentially compensated for by other genes.
Inheritance of an autosomal recessive trait. (Wikimedia Commons, GFDL)
Secondly, sometimes traits (including diseases) are recessive, which means that you need more than one bad gene version (or allele) to make the effects noticeable. Otherwise the dominant variant makes up for it.
Thirdly, the ill effects of the flawed gene variant might manifest late in life, or require additional stimuli in order to develop.
Lastly, as I wrote earlier, the effects can be relatively mild, leading to a ‘healthy’ classification, since health and disease are more like points on a continuum than clearly separated categories.
There are probably more reasons. Feel free to add one or more in the comments.
Besides the numbers (400 and 2) aren’t that bad considering that each of us probably carries a few millions of mutations. However, the authors state:
“…our current best mean estimates of ∼400 damaging variants and ∼2 bona fide disease mutations per individual are likely to increase rather than decrease as sequencing studies ascertain rare variants more effectively and as additional disease alleles are discovered.”
The new plan of the NHS looks like it can make significant contributions here.
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Xue, Y., Chen, Y., Ayub, Q., Huang, N., Ball, E., Mort, M., Phillips, A., Shaw, K., Stenson, P., Cooper, D., & Tyler-Smith, C. (2012). Deleterious- and Disease-Allele Prevalence in Healthy Individuals: Insights from Current Predictions, Mutation Databases, and Population-Scale Resequencing The American Journal of Human Genetics, 91 (6), 1022-1032 DOI: 10.1016/j.ajhg.2012.10.015
Great post – it’s been included in the 55th Carnival of Evolution on Genome Engineering at http://tinyurl.com/55thCoE