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Expanding carrier screening: beyond the genes, to include underrepresented ancestries

Year: 2025

Type: article

Abstract: Reproductive carrier screening has evolved beyond ethnic-specific testing to include diverse populations, yet gene selection varies considerably. In Singapore, genomic data analysis identified severe paediatric conditions amongst Chinese, Indian and Malay populations absent from existing screening panels. We developed a model leveraging data from 9051 participants to guide gene selection for carrier screening representative of Asian genetic diversity, focusing on severe paediatric-onset conditions prevalent in these populations. After evaluating severity, genotype-phenotype variability, clinical utility and technical feasibility, we identified 88 genes associated with recessive severe paediatric onset prevalent amongst Chinese, Indian and Malay populations, irrespective of carrier frequency. Including 24 additional genes from our registry resulted in a 105-gene panel, predicted to identify 0.44% at-risk couples, with 86 genes overlapping existing panels. Broadening criteria to include moderate severity conditions while limiting carrier frequencies to less than 1 in 200 reduced the panel to 59 genes, increasing predicted at-risk couples to 0.47%, due to higher carrier frequencies, yet introducing counselling complexities from greater clinical variability. Using local genomic data, we identified genetic conditions relevant to Asian populations for carrier screening. Expanding national genomic sequencing initiatives provides an opportunity to assess genetic condition prevalence across diverse ancestries, improving equity in carrier screening programmes.

Source: npj Genomic Medicine

DOI: 10.1038/s41525-025-00545-w