AZF缺失患者Y染色体断裂点定位分析

Breakpoint localization of Y-chromosome massive deletions in 49 spermatogenesis dysfunction patients

目的分析导致无精子因子区域（azoospermiafactor，AZF）缺失的Y染色体断裂的特点。方法在272例无精子症、240例严重少精子症患者进行Y染色体AZF微缺失筛查基础上，对筛查发现大片段缺失的49例患者，选择AZFa、AZFb、AZFc区23个序列标签位点（sequencetaggedsite，STS），对断裂点进行定位分析。颖有无精子症缺失基因家族（deletedinazoospermia，DAz）、基因部分拷贝缺失病例进行单核苷酸多态性（singlenuecleotidevarians，SNV）缺失分析以确定DAZ基因的拷贝数。结果6例AZFb＋c缺失患者，1例为sY98／sY1206缺失，4例为P5／P1远端重组，1例为P4／P1远端重组。3例筛查发现AZFb区缺失患者，1例为P5／P3缺失，2例为PS／P1近端重组，伴有DA幼、DAZ2拷贝缺失。40例AZFc区全缺失患者，均为b2／b4同源重组。部份AZFb、AZFb＋c缺失患者，睾丸穿刺活检发现精子生成减少或精子成熟障碍。结论对Y染色体AZF大片段缺失断裂点的大致定位有利于判断缺失发生机制，进而分析丢失的生精相关基因拷贝性质与数量，以评价其与生精障碍表型之间的关联。

Objective To analyze the characteristics of azoospermia factor （AZF） deletions in Y chromosome. Methods Based on the AZF microdeletion screening on 272 cases of azoospermia and 240 cases of severe oligozoo spermia, 49 cases were investigated using 23 sequence-tagged sites （STS） in AZFa, AZFb and AZFc. For some cases, single nucleotide rarians（SNV） method was applied to identify the single nucleotide polymorphism（SNPs） in four DAZ gene copies and to determine the copy number of the DAZ gene. Results In 6 cases with deletions of AZFb＋c, there was 1 case with sY98/sY1206 deletion, 4 cases with P5/distal-P1 recombination and 1 with P4/distal-P1 recombination. In 3 cases with deletions in AZFb, 1 case showed P5/P3 deletion and 2 cases showed P5/proximal P1 recombination with DAZl and DAZ2 deletions, b2/b4 recombination was observed in all the 40 cases with deletions in AZFc. A fraction of patients with AZFh and AZFb＋e deletions showed oligospermia and spermatogenic failure by testicular biopsy. Conclusion Breakpoint localization of deletions in AZF regions may help elucidating the mechanisms of microdeletions, and analysis of the characteristics and quantity of deleted genes essential for normal spermatogenesis may evaluate the association of phenotype with spermatogenic failure.