title: Fragile X "gray zone" alleles: AGG patterns, expansion risks, and associated haplotypes.
abstract: The risk for fragile X "gray-zone" alleles to expand appears to depend on the absence of stabilizing AGGs, which interrupt the CGG repeat region. To characterize such alleles better, we analyzed a series of 101 chromosomes with triplet repeat lengths ranging from 35 to 59 for variations in their AGG interspersion patterns. Among these, 11.9% had 3 AGGs, 59.3% had 2, 24.8% had 1, and 4.0% had 0. An inverse relationship between FMR1 repeat length and the number of interrupting AGGs was observed. Within the range of 35-44 repeats, 98.7% of alleles were found to have a pure CGG repeat length (PCGG) of less than 33. However, among alleles with 45-59 repeats, 50% were found to have 0 or 1 AGG and a PCGG of more than 33. Thus, gray-zone alleles with 45-59 repeats frequently have a long stretch of pure CGGs and thus are more likely to be unstably inherited than alleles with 35-44 repeats. We found length associations of PCGG with 2 flanking microsatellites, DXS548 and FRAXAC1: a PCGG < or = 20 was strongly associated with haplotype 20-19, whereas a PCGG > 20 was more strongly associated with the haplotype 25-21. This result could reflect a founder effect or a generalized instability of CGGs and microsatellites.
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research, Staten Island 10314, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zhong
authors.forename: W
authors.initials: W
authors.lastname: Ju
authors.forename: J
authors.initials: J
authors.lastname: Pietrofesa
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Dobkin
authors.forename: W T
authors.initials: WT
authors.lastname: Brown
mesh_terms: D000483:Alleles; D005600:Fragile X Syndrome / Q000453:epidemiology / Q000235:genetics*; D005819:Genetic Markers; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D018570:Risk Assessment; D012307:Risk Factors; D018911:Trinucleotide Repeats
chemical_list: D005819:Genetic Markers