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

Area of Science:

• Genetics
• Reproductive Health
• Genomic Medicine

Background:

• Reproductive carrier screening has shifted from ethnic-specific to broader population inclusion.
• Gene selection for carrier screening panels remains inconsistent across diverse populations.
• Genomic data from Singapore revealed severe pediatric conditions in Chinese, Indian, and Malay populations not covered by existing panels.

Purpose of the Study:

• To develop a gene selection model for carrier screening that reflects Asian genetic diversity.
• To identify genes associated with severe pediatric-onset conditions prevalent in Chinese, Indian, and Malay populations.
• To enhance equity in carrier screening programs by incorporating local genomic data.

Main Methods:

• Leveraged genomic data from 9051 participants to guide gene selection.
• Evaluated genes based on severity, genotype-phenotype variability, clinical utility, and technical feasibility.
• Developed a 105-gene panel focusing on severe recessive pediatric-onset conditions.

Main Results:

• Identified 88 genes associated with severe pediatric-onset recessive conditions prevalent in Asian populations.
• A 105-gene panel was created, with 86 genes overlapping existing panels.
• A 59-gene panel focusing on moderate severity conditions identified 0.47% at-risk couples, but introduced counseling complexities.

Conclusions:

• Local genomic data identified genetic conditions relevant for carrier screening in Asian populations.
• Expanding national genomic sequencing can improve carrier screening equity across diverse ancestries.
• The developed gene panel enhances reproductive carrier screening for Asian populations.