Brightwell Gale, Wycherley Rachel, Potts Gemma, Waghorn Andrew
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK.
J Hum Genet. 2002;47(11):567-75. doi: 10.1007/s100380200087.
Single-nucleotide polymorphisms (SNPs) are the most common type of genetic variation within the human genome, occurring approximately once every kilobase. However, for association studies, SNPs are not as informative as microsatellite markers and a large number of SNPs and substantial population sizes are required for linkage and mapping studies. A SNP map was generated for the FRAX region of the X chromosome, approximately 0.8 Mb proximal and 1.8 Mb distal to the FRAXA repeat, at a density of at least 1 SNP every 100 kb. SNPs were identified in a population of 28 women with a FRAXA expan-sion (including three women with a FRAXE expansion) on a background of different DXS548, CA1 and CA2 haplotypes, and a normal X chromosome with a different microsatellite haplotype. Fifty-four polymorphisms were identified in a total of 52 257 bp distributed over 2.6 Mb. This represented about 1 SNP every 1024 bp, which was consistent with a nondesert region (1 : 1000 bp). Because the SNPs identified in this study have haplotype and frequency data from an affected population, they should provide a useful resource for researchers to investigate the genetic mechanisms behind instability and expansion of both FRAXA and FRAXE triplet repeats.
单核苷酸多态性（SNPs）是人类基因组中最常见的遗传变异类型，大约每千碱基出现一次。然而，对于关联研究而言，SNPs的信息量不如微卫星标记，连锁和定位研究需要大量的SNPs和足够大的群体规模。在X染色体的FRAX区域生成了一个SNP图谱，该区域位于FRAXA重复序列近端约0.8 Mb和远端约1.8 Mb处，密度至少为每100 kb有1个SNP。在28名携带FRAXA扩增（包括3名携带FRAXE扩增）的女性群体中，背景为不同的DXS548、CA1和CA2单倍型，以及一条具有不同微卫星单倍型的正常X染色体，鉴定出了SNPs。在分布于2.6 Mb的总共52257 bp中鉴定出了54个多态性位点。这相当于大约每1024 bp有1个SNP，与非荒漠区域（1:1000 bp）一致。由于本研究中鉴定出的SNPs具有来自患病群体的单倍型和频率数据，它们应为研究人员提供有用的资源，以研究FRAXA和FRAXE三联体重复序列不稳定和扩增背后的遗传机制。
