Survey of the fragile X syndrome CGG repeat and the short-tandem-repeat and single-nucleotide-polymorphism haplotypes in an African American population.

Crawford DC, Schwartz CE, Meadows KL, Newman JL, Taft LF, Gunter C, Brown WT, Carpenter NJ, Howard-Peebles PN, Monaghan KG, Nolin SL, Reiss AL, Feldman GL, Rohlfs EM, Warren ST, Sherman SL
Am J Hum Genet. 2000 66 (2): 480-93

PMID: 10677308 · PMCID: PMC1288101 · DOI:10.1086/302762

Previous studies have shown that specific short-tandem-repeat (STR) and single-nucleotide-polymorphism (SNP)-based haplotypes within and among unaffected and fragile X white populations are found to be associated with specific CGG-repeat patterns. It has been hypothesized that these associations result from different mutational mechanisms, possibly influenced by the CGG structure and/or cis-acting factors. Alternatively, haplotype associations may result from the long mutational history of increasing instability. To understand the basis of the mutational process, we examined the CGG-repeat size, three flanking STR markers (DXS548-FRAXAC1-FRAXAC2), and one SNP (ATL1) spanning 150 kb around the CGG repeat in unaffected (n=637) and fragile X (n=63) African American populations and compared them with unaffected (n=721) and fragile X (n=102) white populations. Several important differences were found between the two ethnic groups. First, in contrast to that seen in the white population, no associations were observed among the African American intermediate or "predisposed" alleles (41-60 repeats). Second, two previously undescribed haplotypes accounted for the majority of the African American fragile X population. Third, a putative "protective" haplotype was not found among African Americans, whereas it was found among whites. Fourth, in contrast to that seen in whites, the SNP ATL1 was in linkage equilibrium among African Americans, and it did not add new information to the STR haplotypes. These data indicate that the STR- and SNP-based haplotype associations identified in whites probably reflect the mutational history of the expansion, rather than a mutational mechanism or pathway.

MeSH Terms (19)

African Americans African Continental Ancestry Group Alleles Child European Continental Ancestry Group Fragile X Syndrome Gene Frequency Genetic Linkage Genetic Markers Genetic Testing Haplotypes Heterozygote Humans Male Mutagenesis Polymorphism, Single Nucleotide Tandem Repeat Sequences Trinucleotide Repeat Expansion United States

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