Journal Article

Fragile X CGG repeat structures among African-Americans: identification of a novel factor responsible for repeat instability

Dana C. Crawford, Fuping Zhang, Beth Wilson, Stephen T. Warren and Stephanie L. Sherman

in Human Molecular Genetics

Volume 9, issue 12, pages 1759-1769
Published in print July 2000 | ISSN: 0964-6906
Published online July 2000 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/9.12.1759
Fragile X CGG repeat structures among African-Americans: identification of a novel factor responsible for repeat instability

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The cryptic CGG repeat responsible for the fragile X syndrome, located in the 5′-UTR of FMR1, is unique compared with the many other triplet repeat-causing diseases, making it ideal for identifying factors involved in repeat expansion that may be common to other triplet repeat diseases. To date, a number of factors have been identified which may influence repeat instability, including the number and position of interspersed AGGs, length of the 3′ pure CGG repeat and haplotype background. However, nearly all such data were derived from studies of Caucasians. Using a large African-American population, we present the only comprehensive examination of factors associated with CGG repeat instability in a non-Caucasian population. Among Caucasians, susceptible alleles were thought to come from those in the intermediate repeat range (41–60 repeats); however, we find that susceptible alleles may come from a larger repeat pool (35–60 repeats) and are better defined by their pure CGG repeat and/or ­presence of only one AGG interruption. These results demonstrate the existence of different susceptible alleles among world populations and may account for the similar prevalence of the fragile X syndrome in African-Americans compared with Caucasians despite the lower frequency of inter­mediate sized alleles in the African-American population. Finally, we show that repeat structures among unaffected African-Americans with the most frequent fragile X haplotype background are either pure or contain a single distal interruption. We propose that the lack of a proximal most interruption is a novel factor involved in CGG repeat instability.

Journal Article.  8361 words.  Illustrated.

Subjects: Genetics and Genomics

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