Sirugo G, Cocozza S, Brice A, Cavalcanti F, De Michele G, Dones I, Filla A, Koenig M, Lorenzetti D, Monticelli A
Institut de Chimie Biologique, INSERM U-184, CNRS-LGME, Strasbourg, France.
Eur J Hum Genet. 1993;1(2):133-43. doi: 10.1159/000472400.
We investigated linkage disequilibrium between Friedreich's ataxia (FRDA) and four tightly linked multi-allele markers in 140 families from France and Italy. These markers include three microsatellites (D9S111, D9S15 and D9S110) and one RFLP (D9S5). Their chromosomal order, D9S111-D9S15-D9S110-D9S5, had previously been established by physical mapping. Linkage disequilibrium was evaluated between each marker and FRDA and between markers. Extended haplotypes were obtained and their frequencies on FRDA and normal chromosomes were evaluated. We obtained evidence of strong allelic association of FRDA with D9S5 only. Analysis of linkage disequilibrium between markers revealed a significant decrease between D9S110 and D9S5, suggesting the presence of a recombination hot spot in the interval between these markers. Probably for this reason, no major FRDA-associated extended haplotype could be identified. Our data suggest the presence of a few common disease-causing mutations in the examined population, and indicate a putative localization for the FRDA gene. Transcribed sequences have been found in this candidate region.
我们在来自法国和意大利的140个家庭中研究了弗里德赖希共济失调（FRDA）与四个紧密连锁的多等位基因标记之间的连锁不平衡。这些标记包括三个微卫星（D9S111、D9S15和D9S110）和一个限制性片段长度多态性（RFLP，D9S5）。它们的染色体顺序D9S111-D9S15-D9S110-D9S5先前已通过物理图谱确定。评估了每个标记与FRDA之间以及标记之间的连锁不平衡。获得了扩展单倍型，并评估了它们在FRDA和正常染色体上的频率。我们仅获得了FRDA与D9S5之间存在强等位基因关联的证据。标记之间的连锁不平衡分析显示D9S110和D9S5之间有显著下降，表明在这些标记之间的区间存在一个重组热点。可能由于这个原因，未发现与FRDA相关的主要扩展单倍型。我们的数据表明在所研究的人群中存在一些常见的致病突变，并指出了FRDA基因的一个假定定位。在这个候选区域已发现转录序列。
