Expansion mutation frequency and CGG/GCC repeat polymorphism inFMR1 andFMR2 genes in an Indian population

Abstract

Based on molecular screening, we estimated the frequencies of fragile X syndrome and FRAXE syndrome in an institutionalized population (n = 130) in New Delhi, India. Eligibility criteria for inclusion of subjects in the study were mild/moderate mental retardation, with/without family history, and the fragile X clinical phenotype. Screening by Southern hybridization revealed an overall frequency of 0.077 of the syndrome in the sample population. The disorder was observed with a high frequency (0.1) among males as compared to females (0.027). No expansions of FMR2 allele were observed in the same study sample. CGG/GCC allelic polymorphism of FMR1 and FMR2 were established from a total of 392 X chromosomes, using the radioactive polymerase chain reaction–polyacrylamide gel electrophoresis method. Distinct repeat sizes, repeat ranges, and repeat modes characterised the FMR1 and FMR2 alleles. In the X chromosomes of both MR individuals and unaffected controls, unimodal values of 29 and 15 repeats in FMR1 and FMR2 genes, respectively, were observed. Allele frequency distribution was symmetrical at the FMR1 locus whereas a significant positive skew was observed for the FMR2 alleles. The observed heterozygosity of the FMR1 gene was 0.772 compared to 0.839 of FMR2. Correlation of CGG/GCC repeats of FMR1 and FMR2 did not show any association of repeat sizes at these two loci (correlation coefficient, ρ = 0.09). CGG/GCC repeat variation at FMR1 and FMR2 loci observed in this study sample are different from that reported for the other Caucasian and Asian populations. Genet. Epidemiol. 20:129–144, 2001. © 2001 Wiley‐Liss, Inc.

Distribution of CGG repeat sizes within the fragile X mental retardation 1 ( FMR1 ) homologue in a non-human primate population

“…(Arinami et al 1993;Brown et al 1996;Pang et al 1999). The breadth of the allele size distribution in macaques, ranging from 16 -54 CGG repeats, is also quite similar to the previously reported human allele distributions (Faradz et al 2000;Sharma et al 2001). Both the allele distribution and estimated (lower bound) heterozygosity (111/265= 0.419) for the FMR1 gene in female macaques is strikingly similar to the corresponding values reported by Pang et al (1999), who studied 999 human X chromosomes.…”

Analysis of FMR1 (CGG)n alleles and DXS548-FRAXAC1 haplotypes in three European circumpolar populations: traces of genetic relationship with Asia

“…The distribution of Norwegian (CGG) n repeats were similar to distributions reported in Caucasian populations, 11 while the Nenets population had a higher (P50.05) proportion of 29 CGG alleles compared to the Norwegian and Saami population and the Saami allele distribution displayed a broader peak around 30 CGG.…”

Fragile X screening for FRAXA and FRAXE mutations using PCR based studies: Results of a five year study

“…For FRAXA mutation using double digestion of genomic DNA with Eco RI and EagI and Southern blots were hybridized with probe pp2 [5] . Southern blotting was carried out in Dr. B.K.…”

“…[2] Few studies in Indian population show the frequency of Fragile X (A) syndrome among idiopathic mentally retarded (MR) males as approximately 7%. [3][4][5] Fragile X syndrome is caused by mutation of the FMR 1 gene on the X chromosome. This site is present at Xq27.3 and the gene spans 39 Kb containing 17 exons.…”