Common gene variants change how a rare cleft palate mutation plays out
Researchers, including a team at the University of Texas Health Science Center, studied a three-generation family with non-syndromic cleft lip and palate. Whole-genome sequencing, genotyping, polygenic risk score analysis and linkage analysis turned up a rare PDGFRA missense variant (p.R914W) tied to the condition. Family members who carried the variant but showed no cleft had lower polygenic risk scores than those who did. In lab tests the variant lost its signaling activity, and disrupting pdgfra in zebrafish embryos produced unilateral orofacial clefting.
The study, based on cell and zebrafish experiments, backs a model in which common genetic variants modify how a rare mutation plays out.
Source: Polygenic risk impacts PDGFRA mutation penetrance in non-syndromic cleft lip and palate. (doi.org).
Written by the Genomes desk from the primary source linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].
- UK Biobank expands genetic analysis to diverse ancestry groups September 18, 2025
- FinnGen study finds 30 new disease associations in Finnish population January 18, 2023
- GWAS Catalog adds sequencing data, links to Polygenic Score Catalog January 1, 2023
- Polygenic scores lose accuracy fast across UK Biobank ancestry groups January 1, 2022
- Diabetes subtypes traced to different genetic drivers November 4, 2021