Resources for Genetics Professionals — Genetic Disorders Associated with Founder Variants Common in the Choctaw Population
Stephanie E Wallace, MD and Lora JH Bean, PhD.
Author Information and AffiliationsInitial Posting: February 6, 2020; Last Revision: June 1, 2023.
Estimated reading time: 1 minute
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 Choctaw 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 Choctaw Population
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| Gene | Disorder | MOI | DNA
Nucleotide
Change | Predicted
Protein
Change | % of Pathogenic
Variants in Gene | Carrier
Frequency | Ethnicity
(Specific Region) | Reference
Sequences | References |
|---|
|
MPL
| Congenital amegakaryocytic thrombocytopenia (OMIM 604498) | AR | c.268C>T | p.Arg90Ter | 40% | Unknown | Choctaw
(Mississippi) |
NM_005373.3
NP_005364.1
|
Newman et al [2017]
|
| c.1609C>T | p.Arg537Trp | 60% |
Included if ≤3 pathogenic variants account for ≥50% of variants identified in a specific ethnic group
AR = autosomal recessive; MOI = mode of inheritance
References
Newman LA, Luter MA, Davis DB, Abdul-Rahman OA, Johnson JM, Megason GC. Congenital amegakaryocytic thrombocytopenia: a case series indicating 2 founder variants in the Mississippi band of Choctaw Indians.
J Pediatr Hematol Oncol. 2017;39:573–5. [
PubMed: 28697167]
