Genetic Diversity of the Fragile X Syndrome Gene (FMR1) in a Large Sub-Saharan West African Population

• Authors: Emmanuel K. Peprah, Emory University; Emily Allen, Emory University; Scott M. Williams, Vanderbilt University; Laresa M. Woodard, Emory University; Stephanie Sherman, Emory University
• Journal Title: Annals of Human Genetics
• Volume: Volume 74, Number 4
• Publisher: Wiley: 12 months | 2010-07-01, Pages 316-325
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/j.1469-1809.2010.00582.x
• Subjects: Biology, Genetics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Genetics & Heredity; FMR1; african population; haplotype; trinucleotide repeat; SINGLE-NUCLEOTIDE-POLYMORPHISM; CGG-REPEAT; LINKAGE DISEQUILIBRIUM; FOUNDER CHROMOSOMES; HELLENIC POPULATION; MENTAL-RETARDATION; CA REPEATS; EXPANSION; HAPLOTYPES; LOCUS

Abstract

Summary: Fragile X syndrome (OMIM #300624) is caused by the expansion of a CGG trinucleotide repeat found in the 5′ untranslated region of the X-linked FMR1 gene. Although examinations of characteristics associated with repeat instability and expansion of the CGG repeat upon transmission from parent to offspring has occurred in various world populations, none has been conducted in large Sub-Saharan African populations. We have examined the FMR1 CGG repeat structure in a sample of 350 males drawn from the general population of Ghana. We found that Ghanaians and African Americans have similar allele frequency distributions of CGG repeat and its flanking STR markers, DXS548 and FRAXAC1. However, the distribution of the more complex marker, FRAXAC2, is significantly different. The haplotype structure of the FMR1 locus indicated that Ghanaians share several haplotypes with African Americans and Caucasians that are associated with the expanded full mutation. In Ghanaians, the majority of repeat structures contained two AGG interruptions, however, the majority of intermediate alleles (35-49) lacked AGG interruptions. Overall, we demonstrate that allelic diversity of the FMR1 locus among Ghanaians is comparable to African Americans, but includes a minority of CGG array structures not found in other populations.