Assessing risk for Mendelian disorders in a Bronx population

Area of Science:

• Genetics
• Medical Genomics

Background:

• Mendelian disorders affect diverse ethnic groups, necessitating population-specific genetic variant identification.
• Understanding variant prevalence is crucial for developing targeted genetic screening and diagnostic tools.

Purpose of the Study:

• To identify genetic variants linked to Mendelian disorders in African American, Puerto Rican, and Dominican populations in the Bronx.
• To assess the utility of these variants for genetic screening panels and whole exome sequencing filters.
• To estimate the prevalence of these variants within the studied populations.

Main Methods:

• High-density oligonucleotide screening of 192 individuals from each of the three ethnic groups.
• Cross-referencing identified variants with next-generation sequencing data.
• Manual curation of variants for clinical validity and utility using the American College of Medical Genetics (ACMG) scoring system.
• Literature review to identify additional relevant variants.

Main Results:

• A panel of 75 variants was identified, representing 39 Mendelian disorders.
• These variants encompass various inheritance patterns, including autosomal dominant, autosomal recessive, digenic recessive, X-linked recessive, and X-linked dominant.
• The identified variants are relevant to the genetic landscape of the studied Bronx populations.

Conclusions:

• The developed variant panel can enhance genetic screening and diagnostic capabilities for Mendelian disorders.
• Broader screening for a wider range of disorders facilitates early or presymptomatic diagnosis.
• Informed genetic screening empowers reproductive choices for individuals and families.