Resources for Genetics Professionals — Genetic Disorders Associated with Founder Variants Common in the Yup'ik Population
Stephanie E Wallace, MD and Lora JH Bean, PhD.
Author Information and AffiliationsInitial Posting: January 10, 2019; Last Revision: June 30, 2022.
Estimated reading time: 2 minutes
A founder variant is a pathogenic variant observed at high frequency in a specific population due to the presence of the variant in a single ancestor or small number of ancestors. The presence of a founder variant can affect the approach to molecular genetic testing. When one or more founder variants account for a large percentage of all pathogenic variants found in a population, testing for the founder variant(s) may be performed first. The table below includes common founder variants — here defined as three or fewer variants that account for >50% of the pathogenic variants identified in a single gene in individuals of a specific ancestry – in individuals of Yup'ik ancestry. Note: Pathogenic variants that are common worldwide due to a DNA sequence hot spot are not considered founder variants and thus are not included.
Table.
Genetic Disorders Associated with Founder Variants Common in the Yup'ik Population
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- 1.
This percentage does not account for the possibility of rare de novo pathogenic variants occurring in this population.
- 2.
To date, no additional pathogenic variants in this gene have been reported in individuals of Yup'ik descent.
- 3.
Calculated carrier frequency based on the incidence of the disorder in individuals of Yup'ik ancestry; estimated carrier frequency is not based on molecular testing of the population.
- 4.
Analysis of CYP21A2 is complicated by the presence of a highly homologous pseudogene, CYP21A1P. Common pathogenic variants (including c.293-13C>G) in the active CYP21A2 arose from recombination and gene conversion with the pseudogene.
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