Geneticists tap human knockouts

Geneticists tap human knockouts

Sequenced genomes reveal mutations that disable single genes and can point to new drugs. (http://www.nature.com/news/geneticists-tap-human-knockouts-1.16239)

For decades, biologists have studied gene function by inactivating the gene in question in mice and other lab animals, and then observing how it affects the organism. Now researchers studying such gene ‘knockouts’ have another, ideal model at their disposal: humans.

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His group and others had been focusing on genome data, but they are now also starting to mine patient-health records to determine the — sometimes subtle — effects of the mutations. In a study of more than 36,000 Finnish people, published in July (E. T. Lim et al. PLoS Genet. 10, e1004494; 2014), a team that included MacArthur discovered that people lacking a gene called LPA might be protected from heart disease, and that another knockout mutation, carried in one copy of a gene by up to 2.4% of Finns, may cause fetuses to miscarry if it is present in both copies.

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The poster child for human-knockout efforts is a new class of drugs that block a gene known as PCSK9 (see Nature 496, 152–155; 2013). The gene was discovered in French families with extremely high cholesterol levels in the early 2000s. But researchers soon found that people with rare mutations that inactivate one copy of PCSK9 have low cholesterol and rarely develop heart disease. The first PCSK9-blocking drugs should hit pharmacies next year, with manufacturers jostling for a share of a market that could reach US$25 billion in five years.