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New genomics study shows ancestry could help solve disease riddles

esearch for Scripps Health's genomic medicine program, and director of biostatistics and bioinformatics at STSI, "but it could be that they're still searching in the noise."

The new work offers a likely filter for much of that noise. The results show that comparing a person's DNA sequence against existing genomes for those whose ancestry is not sufficiently similar, as is typically the case, can cause serious problems. Countless differences that seem unique to a patient might instead be DNA variants carried by everyone with the same ancestry. A researcher might, for instance, identify hundreds of variants and not be able to zero in on the one responsible for a disease.

But the new results show that comparing closer ancestry matches will dramatically reduce the number of variants identified as potentially responsible for a disease, reducing a search to a workable number.

For the work, the team developed a tool called the Scripps Genome Adviser. This processing framework uses a supercomputer to incorporate a variety of databases and algorithms to identify DNA variants in a particular genome relative to reference genomes. It then uses algorithms to analyze these variants and predict whether they have any physiological effects, and if so what those might be.

The team began with nearly 60 whole human genome databases and ran three key types of computing experiments. First the researchers identified the number of variants in the reference human genomes and found that on average each has millions of variants, about 12,000 of which have functional effects. Then the scientists looked at the rates at which variants appeared in various ancestry lines.

Honoring Ancestry

Importantly, the scientists didn't stop there. They deliberately inserted a mutation known to cause disease into a genome, then ran this genome through the Adviser to see how effectively it could identify that known variant as unique.


Contact: Mika Ono
Scripps Research Institute

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