Zhong N, Dobkin C, Brown W T
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Nat Genet. 1993 Nov;5(3):248-53. doi: 10.1038/ng1193-248.
While studying founder chromosomes in the fragile X syndrome, we have unexpectedly found linkage equilibrium to FRAXAC2, an Alu-associated microsatellite within the defective gene, FMR-1. DNA sequencing of 265 chromosomes revealed 39 alleles and a complex microsatellite of form (GT)x-C-(TA)y-(T)z. A mutation rate of 3.3% was observed but only among fragile X maternally derived meioses. Finding a second mutable locus within FMR-1 suggests that the target for tandem repeat instability may not be confined to the (CGG)n repeat alone and raises the possibility of an FMR-1 mutation mechanism involving microsatellites.
在研究脆性X综合征的奠基者染色体时，我们意外地发现与FRAXAC2处于连锁平衡状态，FRAXAC2是缺陷基因FMR-1内一个与Alu相关的微卫星。对265条染色体进行DNA测序，发现了39个等位基因以及一个形式为(GT)x-C-(TA)y-(T)z的复杂微卫星。观察到突变率为3.3%，但仅在脆性X母系来源的减数分裂中。在FMR-1内发现第二个可变位点表明，串联重复不稳定性的靶点可能不仅限于单独的(CGG)n重复，这增加了一种涉及微卫星的FMR-1突变机制的可能性。
