A SURVEY OF FRAXE ALLELE SIZES IN 3 POPULATIONS

FRAXE is a fragile site located at Xq27-8, which contains polymorphic triplet GCC repeats associated with a CpG island, Similar to FRAXA, ex pansion of the GCC repeats results in an abnormal methylation of the C pG island and is associated with a mild mental retardation syndrome (F RAXE-MR). We surveyed the GCC repeat alleles of FRAXE from 3 populatio ns. A total of 665 X chromosomes including 416 from a New York Euro-Am erican sample (259 normal and 157 with FRAXA mutations), 157 from a Ch inese sample (144 normal and 13 FRAXA), and 92 from a Finnish sample ( 56 normal and 36 FRAXA) were analyzed by polymerase chain reaction, Tw enty-seven alleles, ranging from 4 to 39 GCC repeats, were observed, T he modal repeat number was 16 in the New York and Finnish samples and accounted for 24% of all the chromosomes tested (162/665). The modal r epeat number in the Chinese sample was 18. A founder effect for FRAXA was suggested among the Finnish FRAXA samples in that 75% had the FRAX E 16 repeat allele versus only 30% of controls, Sequencing of the FRAX E region showed no imperfections within the GCC repeat region, such as those commonly seen in FRAXA, The smaller size and limited range of r epeats and the lack of imperfections suggests the molecular mechanisms underlying FRAXE triplet mutations may be different from those underl ying FRAXA. (C) 1998 Wiley-Liss, Inc.