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‘Ancestry problem’ Sends CRISPR Astray in Some People

Reference genomes used to direct the gene editor fail to account for human diversity in those of African descent

Jocelyn Kaiser

Science, 2022

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CRISPR has amazing promise – the ability to edit any gene. But it needs an RNA “guide sequence” to direct it to the gene it is supposed to edit (and ideally, only to that gene). Such guide sequences are usually made by looking at a set of reference genomes. However, these reference genomes come from only a few people, and do not capture the genetic diversity of much of humanity. CRISPR techniques will thus not work as well in populations whose genomes are not included, especially people with African ancestry, whose genomes are more diverse than those of other populations. Scientists are now working on tools that can include those who have previously been left out.

Summary

CRISPR needs a specific RNA sequence to guide it to its target.

CRISPR has made it technically feasible to edit genes in animals, plants and people. When scientists want to design CRISPR to edit a certain gene, they start by designing an RNA sequence that matches part of that gene’s DNA sequence. This “guide RNA” is essential, as it brings CRISPR’s DNA-cutting enzyme to the proper place in the genome to cut.

These guide RNA sequences are usually generated by looking at reference genomes to find appropriate sequences near the target gene. But these reference genomes come from only a small, relatively homogenous group of people. People from...

About the Author

Jocelyn Kaiser is a staff writer for Science magazine.

‘Ancestry problem’ Sends CRISPR Astray in Some People

Reference genomes used to direct the gene editor fail to account for human diversity in those of African descent

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CRISPR needs a specific RNA sequence to guide it to its target.

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