Bartoloni L, Horrigan S K, Viles K D, Gilchrist J M, Stajich J M, Vance J M, Yamaoka L H, Pericak-Vance M A, Westbrook C A, Speer M C
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60607, USA.
Genomics. 1998 Dec 1;54(2):250-5. doi: 10.1006/geno.1998.5579.
Limb-girdle muscular dystrophy type 1A (LGMD1A) is an autosomal dominant disease characterized by progressive weakness of the hip and shoulder girdle. The gene for LGMD1A had been localized to a 7-cM interval at 5q31 in a single large family (Family 39). To refine the localization of LGMD1A further and to aid in its identification, a high-resolution physical map of the locus was used to identify and provisionally localize 25 polymorphic markers. A subset of these markers was then ordered genetically, using a CEPH meiotic breakpoint panel, resulting in an integrated physical-genetic map of the locus. Relevant markers were genotyped on the members of Family 39 who contained informative recombination events, resulting in a further narrowing of LGMD1A to an interval bounded by D5S479 and D5S594, estimated to be 2 Mb in size. Integration of the genetic and physical map permits the identification of several transcription units from within the narrowed LGMD1A interval, including one that is muscle specific, representing candidate genes for this familial dystrophy.
1A型肢带型肌营养不良症（LGMD1A）是一种常染色体显性疾病，其特征为髋部和肩胛带进行性肌无力。在一个大家族（39号家族）中，LGMD1A基因已被定位于5q31上一个7厘摩的区间。为了进一步精确LGMD1A的定位并协助其鉴定，利用该基因座的高分辨率物理图谱来鉴定并初步定位25个多态性标记。然后使用CEPH减数分裂断点面板对这些标记中的一部分进行遗传排序，从而得到该基因座的综合物理-遗传图谱。对39号家族中发生信息性重组事件的成员进行相关标记的基因分型，结果使LGMD1A进一步缩小至由D5S479和D5S594界定的区间，估计大小为2兆碱基。遗传图谱和物理图谱的整合使得能够在缩小的LGMD1A区间内鉴定出几个转录单位，包括一个肌肉特异性的转录单位，这代表了这种家族性肌营养不良症的候选基因。
