An innovative analysis of shared segments within the genome—an indication of distant "relatedness"—has identified undiagnosed cases of Long QT syndrome, a rare disorder that can lead to abnormal heart rhythms, fainting and sudden cardiac death. The findings, reported in the journal Nature Communications , illustrate the feasibility of the new approach developed by researchers at Vanderbilt University Medical Center to detect undiagnosed carriers of rare disease-causing genetic variants. "Rare genetic diseases are usually studied in referral populations—people who have been referred to specialty clinics for evaluation—but this approach often overestimates the true population impact, which would be better assessed in large non-referral populations, such as biobanks," said Jennifer (Piper) Below, Ph.
D., professor of Medicine in the Division of Genetic Medicine and senior corresponding author of the new study. Because most biobanks recruit participants from the same region, there is often significant undocumented relatedness among the participants, resulting in genomic segments that are shared due to common ancestry—"identical-by-descent" segments, Below explained.
"Identical-by-descent segments give us an opportunity to cluster related people to find rare variants that were present in a common ancestor," she said. To do this, the researchers developed a genetic inference method called DRIVE (Distant Relatedness for Identification and Variant Evaluation). The studies we.
