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Updated: May 3, 2026
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FISH for Pre-implantation Genetic Diagnosis
Published on: February 23, 2011
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Optimizing gene panels for equitable reproductive carrier screening: The Goldilocks approach
Mia J Gruzin1, Matthew Hobbs2, Rachel E Ellsworth3
1Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; School of Clinical Medicine, UNSW Medicine and Health, St Vincent's Clinical Healthcare Campus, Darlinghurst, NSW, Australia.
Summary
Optimizing carrier screening panels with more genes improves detection rates for autosomal recessive and X-linked conditions across diverse populations. This ensures equitable genetic testing by aligning with updated genomic data.
Area of Science:
- Genomics
- Genetic screening
- Population genetics
Background:
- Professional guidelines recommend pan-ancestry carrier screening for genetic conditions.
- The optimal number of genes for carrier screening is not well-defined.
- The American College of Medical Genetics and Genomics (ACMG) proposed 113 genes for screening.
Purpose of the Study:
- To optimize gene content for carrier screening panels considering diverse genetic ancestries.
- To evaluate carrier screening performance using updated population genomic data.
- To ensure equity in genetic carrier screening across different populations.
Main Methods:
- Analyzed ClinVar and gnomAD v4.1.0 data for autosomal recessive and X-linked conditions.
- Modeled carrier screening performance with varying gene panel sizes and compositions.
- Reevaluated the ACMG gene list using updated gnomAD data.
Main Results:
- Identified inconsistencies in ACMG gene lists affecting carrier test performance in underrepresented groups.
- Screening 152, 248, 531, and 725 genes achieved 90%, 95%, 99%, and 99.7% positive yields in couples, respectively.
- Validated models using real-world data from over 60,000 couples.
Conclusions:
- Developed a methodology to optimize carrier screening panels for diverse ancestries.
- Established a framework for continuously updating screening guidelines based on population data.
- Improved equity in genetic carrier screening by ensuring consistency with genomic data.
