Genome-sequencing work has suggested that even healthy humans carry hundreds of 'loss of function' (LoF) mutations that seriously disrupt protein-coding genes. Daniel MacArthur at the Wellcome Trust Sanger Institute in Hinxton, UK, and his colleagues performed extensive analysis on 185 genomes and determined that a typical individual carries around 100 LoF variants, of which about 20 inactivate both copies of a gene.
Most of the common mutations occurred in non-essential genes and didn't seem to affect health. The team also identified many rare LoF variants found in less than 1% of the population, including 47 serious disease mutations in one copy of a gene. By studying differences between the harmful and neutral variants, the scientists developed an algorithm to prioritize mutations found in medical genome sequencing for further investigation.
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Loss-of-function found in droves. Nature 482, 443 (2012). https://doi.org/10.1038/482443a
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DOI: https://doi.org/10.1038/482443a
