Clermont O, Burlet P, Burglen L, Lefebvre S, Pascal F, McPherson J, Wasmuth J J, Cohen D, Le Paslier D, Weissenbach J
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-12, Hôpital des Enfants-Malades, Paris, France.
Am J Hum Genet. 1994 Apr;54(4):687-94.
The gene for autosomal recessive forms of spinal muscular atrophy (SMA) has recently been mapped to chromosome 5q13, within a 4-cM region between the blocks D5S465/D5S125 and MAP-1B/D5S112. We identified two new highly polymorphic microsatellite DNA markers--namely, AFM265wf5 (D5S629) and AFM281yh9 (D5S637)--which are the closest markers to the SMA locus. Multilocus analysis by the location-score method was used to establish the best estimate of the SMA gene location. Our data suggest that the most likely location for SMA is between locus D5S629 and the block D5S637/D5S351/MAP-1B/D5S112/D5S357. Genetic analysis of inbred SMA families, based on homozygosity by descent and physical mapping using mega-YACs, gave additional information for the loci order as follows: cen-D5S6-D5S125/D5S465-D5S435-D5S629-SMA-+ ++D5S637-D5S351-MAP-1B/D5S112-D5S357- D5S39-tel. These data give the direction for bidirectional walking in order to clone this interval and isolate the SMA gene.
常染色体隐性脊髓性肌萎缩症（SMA）的基因最近已被定位到5号染色体的5q13区域，位于D5S465/D5S125和MAP - 1B/D5S112两个区域之间4厘摩的范围内。我们鉴定出两个新的高度多态性微卫星DNA标记——即AFM265wf5（D5S629）和AFM281yh9（D5S637），它们是最靠近SMA基因座的标记。采用定位评分法进行多位点分析以确定SMA基因位置的最佳估计值。我们的数据表明，SMA最可能的位置在基因座D5S629与D5S637/D5S351/MAP - 1B/D5S112/D5S357区域之间。对近亲繁殖的SMA家系进行基于同源纯合性的遗传分析，并使用大型酵母人工染色体（mega - YAC）进行物理图谱分析，得出了如下基因座顺序的更多信息：着丝粒 - D5S6 - D5S125/D5S465 - D5S435 - D5S629 - SMA - +++D5S637 - D5S351 - MAP - 1B/D5S112 - D5S357 - D5S39 - 端粒。这些数据为双向步移提供了方向，以便克隆该区间并分离出SMA基因。
