Reference genomes used to direct the gene editor fail to account for human diversity
By Jocelyn Kaiser – Science
The 10-year-old gene-editing tool known as CRISPR is indispensable for engineering plants, tailoring lab animals, and probing basic biology. But there’s a caveat when it is used to tweak human genes: Unlike lab mice, which are usually inbred and genetically identical, people’s genomes differ individually and by ancestry.
These ancestry differences mean CRISPR doesn’t always edit some genomes as intended, particularly in people of African descent, whose genomes are most likely to differ from those used to steer CRISPR to a specific gene. A new analysis finds that failing to account for ancestry slightly skewed a massive sweep for cancer genes, causing it to miss genes important as drug targets in those of recent African descent.
The study, posted online, “shows a clear example of this [ancestry] problem,” says computational biologist Luca Pinello of the Harvard University–affiliated Massachusetts General Hospital, who has also studied the issue. He and the scientists behind the new work propose tools to avoid it.