Researchers at Texas Children’s Duncan Neurological Research Institute and Baylor College of Medicine have introduced a new tool in the Genome Aggregation Database (gnomAD) that aims to improve the accuracy of genetic testing. The method, called local ancestry inference (LAI), divides the genome into segments based on specific ancestries to provide more precise information about genetic differences.
“This research updates our genomic resources to better reflect the full spectrum of genetic variation,” said Dr. Elizabeth Atkinson, Assistant Professor in the Department of Molecular and Human Genetics at Baylor College of Medicine and principal investigator at the NRI at Texas Children’s. “By refining allele frequency estimates for admixed populations, we can improve the accuracy of genetic diagnoses and reduce the risk of misclassification — ultimately benefitting patients across all backgrounds.”
The study, published in Nature Communications, is titled “Improved Allele Frequencies in gnomAD through Local Ancestry Inference.” Dr. Atkinson is listed as senior author, with Pragati Kore and Michael Wilson as co-first authors.
Genetic testing often relies on average frequencies across large population groups. This approach can miss important distinctions for individuals whose backgrounds include multiple continental ancestries, such as those identified as African/African American or Latino/Admixed American in gnomAD.
To address this issue, Dr. Atkinson’s team used LAI to break down genomes into ancestry-specific segments—such as African, European, or Indigenous American—and then calculated variant frequencies within each segment. They found that many variants previously considered rare globally are actually common within certain ancestry backgrounds.
“These differences are not just academic,” said Dr. Atkinson. “They have clinical consequences.”
The research revealed that over 80% of genetic sites in African/African American and Latino/Admixed American groups had higher frequencies in at least one ancestry-specific tract than earlier reported data suggested. In some cases, these findings shift a variant above a key clinical threshold set by the American College of Medical Genetics and Genomics (ACMG) for classifying variants as benign, which could lead to more accurate reclassification.
Ancestry-specific data from this study is now available through gnomAD for use by researchers and clinicians worldwide.
“Ancestry is complex, and putting a single label on patients is not the most accurate way to diagnose them,” said Dr. Atkinson. “With this research, we are moving toward a more nuanced consideration of ancestry.”
Texas Children’s Hospital continues its focus on advancing pediatric care through patient services, education, and research efforts alongside its partnership with Baylor College of Medicine.
