Hillermann R, See C G, Pook M, Wilkes D, Carvajal J, Doudney K, Williamson R, Chamberlain S
Department of Biochemistry and Molecular Genetics, St. Mary's Hospital Medical School, Imperial College of Science and Technology, London, UK.
Cytogenet Cell Genet. 1995;71(3):214-6. doi: 10.1159/000134112.
Orientation of the Friedreich's ataxia locus (FRDA) with respect to D9S15 and D9S5 has proved critical to the design of subsequent cloning strategies. The rarity of recombination events between FRDA and these markers, originally used to determine assignment to human chromosome region 9q13-->q21.1, has necessitated the instigation of physical mapping studies to determine order and, hence, the precise location of the disease gene. Simultaneous fluorescence in situ hybridisation using cosmid clones located in close proximity to the ends of a 1.2-Mb yeast artificial chromosome clone extending into the FRDA candidate region provides physical evidence for the order of the marker loci to be cen-D9S202-D9S5-D9S15-qter. The possibility that a pericentric inversion, occurring naturally in approximately 1% of the normal population, may affect the order of markers within this region has been eliminated. Considered in association with the interpretation of a recombination event detected in a single affected individual, these data indicate that the FRDA locus is located proximal to D9S5.
事实证明，弗里德赖希共济失调基因座（FRDA）相对于D9S15和D9S5的定位对于后续克隆策略的设计至关重要。最初用于确定其定位于人类染色体区域9q13→q21.1的FRDA与这些标记之间重组事件的罕见性，使得必须开展物理图谱研究以确定顺序，进而确定疾病基因的精确位置。使用位于延伸至FRDA候选区域的1.2兆碱基酵母人工染色体克隆末端附近的黏粒克隆进行同步荧光原位杂交，为标记位点的顺序cen-D9S202-D9S5-D9S15-qter提供了物理证据。在大约1%的正常人群中自然发生的着丝粒周围倒位可能影响该区域内标记顺序的可能性已被排除。结合对在一名受影响个体中检测到的重组事件的解释来看，这些数据表明FRDA基因座位于D9S5的近端。
