Texas Children’s researchers create groundbreaking tool to improve accuracy of genetic testing

(Press-News.org) HOUSTON (Oct. 6, 2025) – Researchers at Texas Children’s Neurological Research Institute (NRI) and Baylor College of Medicine have developed a powerful new tool within the Genome Aggregation Database (gnomAD) to sharpen the accuracy of genetic testing – a breakthrough with direct implications for patient diagnoses and care worldwide.

The work, published in Nature Communications, applies a method called local ancestry inference (LAI), which breaks the genome into ancestry-specific segments to provide more accurate insights into 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 called Improved Allele Frequencies in gnomAD through Local Ancestry Inference, represents a major step forward in the field of genetic testing and personalized medicine. Dr. Atkinson is the senior author of the study, and Pragati Kore and Michael Wilson are co-first authors.

Genetic testing is a powerful tool for diagnosing disease. If genetic variants are common in the general population, they are more likely to be benign. However, estimates for most population frequencies are based on averages across large groups. For people whose genetic background reflects ancestry from multiple continents, such as those classified as African/African American or Latino/Admixed American in gnomAD, this aggregate approach can mask important differences between their ancestral components.

Dr. Atkinson’s team applied local ancestry inference (LAI) to address this problem. Instead of looking at the genome as a whole, LAI breaks it down into segments tracing back to different continental ancestries (for example, African, European, or Indigenous American). The team then calculated how common each variant is within each ancestry segment. This revealed that many variants thought to be rare in global data are actually common in certain ancestry backgrounds.

“These differences are not just academic,” said Dr. Atkinson. “They have clinical consequences.”

Researchers found that in the African/African American and Latino/Admixed American groups, more than 80% of genetic sites had a higher frequency in at least one ancestry-specific tract than previously reported. In some cases, this pushes the variant above a key clinical threshold used by the American College of Medical Genetics and Genomics (ACMG) to classify a variant as benign. This could lead to a more accurate reclassification of variants that might otherwise be misinterpreted.

The new ancestry-specific data is now publicly available through gnomAD, providing researchers, clinicians and genetic testing laboratories all over the world with a more precise tool for interpreting genetic variation.

“Ancestry is a 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.”

About Texas Children’s

Texas Children's, a nonprofit health care organization, is committed to creating a healthier future for children and women throughout the global community by leading in patient care, education and research. Consistently ranked as the best children's hospital in Texas and among the top in the nation, Texas Children's has garnered widespread recognition for its expertise and breakthroughs in pediatric and women's health. The system includes the Texas Children's Duncan NRI; the Feigin Tower for pediatric research; Texas Children's Pavilion for Women, a comprehensive obstetrics/gynecology facility focusing on high-risk births; Texas Children's Hospital West Campus, a community hospital in suburban West Houston; Texas Children's Hospital The Woodlands, the first hospital devoted to children's care for communities north of Houston and Texas Children's Hospital North Austin, the new state-of-the-art facility providing world-class pediatric and maternal care to Austin families. The organization also created Texas Children's Health Plan, the nation's first HMO focused on children; Texas Children's Pediatrics, the largest pediatric primary care network in the country; Texas Children's Urgent Care clinics that specialize in after-hours care tailored specifically for children; and a global health program that is channeling care to children and women all over the world. Texas Children's Hospital is affiliated with Baylor College of Medicine. For more information, visit www.texaschildrens.org. 

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