Allamand V, Broux O, Richard I, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Pereira de Souza A
CNRS URA 1922, Généthon, Evry, France.
Am J Hum Genet. 1995 Jun;56(6):1417-30.
A gene for a recessive form of limb-girdle muscular dystrophy (LGMD2A) has been localized to chromosome 15. A physical map of the 7-cM candidate 15q15.1-q21.1 region has been constructed by means of a 10-12-Mb continuum of overlapping YAC clones. New microsatellite markers developed from these YACs were genotyped on large, consanguineous LGMD2A pedigrees from different origins. The identification of recombination events in these families allowed the restriction of the LGMD2A region to an estimated 1-cM interval, equivalent to approximately 3-4 Mb. Linkage disequilibrium data on genetic isolates from the island of Réunion and from the Amish community suggest a preferential location of the LGMD2A gene in the proximal part of this region. Analysis of the interrelated pedigrees from Réunion revealed the existence of at least six different carrier haplotypes. This allelic heterogeneity is incompatible with the presumed existence of a founder effect and suggests that multiple LGMD2A mutations may segregate in this population.
一种隐性肢带型肌营养不良（LGMD2A）的基因已被定位到15号染色体。通过10 - 12Mb的重叠酵母人工染色体（YAC）克隆连续群构建了15q15.1 - q21.1区域7厘摩（cM）候选区域的物理图谱。从这些YAC中开发的新微卫星标记在来自不同来源的大型近亲LGMD2A家系中进行了基因分型。这些家族中重组事件的鉴定使得LGMD2A区域被限定在估计1cM的区间内，相当于大约3 - 4Mb。来自留尼汪岛和阿米什社区遗传隔离人群的连锁不平衡数据表明LGMD2A基因在该区域近端的优先定位。对来自留尼汪岛相关家系的分析揭示了至少六种不同的携带者单倍型。这种等位基因异质性与假定的奠基者效应的存在不相符，表明多个LGMD2A突变可能在该人群中分离。
