Date of Award

5-2024

Document Type

Thesis - Closed Access

Degree Name

MS in Human Genetics

First Advisor

Claire Davis

Abstract

Carrier screening is used to identify individuals who are at-risk of having a child with a genetic condition. The goal of carrier screening is to allow individuals or couples without a known personal or family history of autosomal recessive (AR) conditions to learn about potential risks that may affect their offspring and to take the steps needed to mitigate such risk. Many countries define preconception and reproductive screening in different terms and screen for different conditions. In 2021, ACMG released its carrier screening practice resource for AR conditions and recommended offering carrier screening during pregnancy and preconception for 97 conditions with a carrier frequency of 1/200 and above in the Genome aggregation database (gnomAD) v2; however, the Middle Eastern population was not represented in the gnomAD v2. Furthermore, genome data from only 158 individuals were included in the 2021 updated version of gnomAD v3. This study aimed to interrogate the rate of carrier frequency for AR conditions based on the genome data from 14,392 individuals included in the Qatar Genome Project. Carrier frequency for pathogenic/likely pathogenic variants in 2,987 genes associated with AR conditions obtained from ClinVar were calculated in the Qatari genomes. Genes with carrier frequency of ≥1/200 were subject to further curation for being associated with moderate to severe clinical presentations. We identified 69 genes with a carrier frequency of ≥1/200 and moderate to severe presentation, of which only 16 genes were shared with the ACMG list of suggested genes for carrier screening. The study also discovered certain genetic conditions with high carrier frequency within the Qatari population, such as immunodeficiency due to CD25 deficiency, spinocerebellar ataxia, combined deafness and blindness, congenital adrenal hyperplasia, and Niemann-Pick disease. This study highlights the importance of incorporating population-specific data into the development of carrier screening programs. Our findings in the Qatari population emphasize the limitations of relying on generalized, global datasets and the need for targeted, population-specific research to accurately identify the genetic diversity and disease prevalence within specific ethnic and regional populations. We propose further research on the implementation of a population-specific carrier screening panel for the Qatari population based on the results of this study that could have a significant impact on reproductive health and care in the Middle East region.

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