男性不育人群17个Y染色体短串联重复基因座无效等位基因分析

Analysis of null alleles for 17 Y chromosome-short tandem repeat loci in infertile males

目的探讨17个Y染色体短串联重复（Y—shorttandemrepeat，Y—STR）在遗传缺陷相关的男性不育群体中基因座分型时无效等位基因现象。方法应用改良多重PCR体系进行序列标签位点（sequencetaggedsites，STS）检测，对236例非梗阻性无精、严重少精男性个体进行Y染色体无精子症因子（azoospermiafactor，AZF）微缺失检测及分型；应用AmpFISTR0YfilerTM体系在上述人群中进行17Y—STR（DYS19、DYS389I、DYS389II、DYS390、DYS391、DYS392、DYS393、DYS437、DY$438、DYS439、DYS385a／b、DYS448、DYS456、DYS458、DYS635、Y—GATA-H4）基因分型。结果上述人群中AZF的总缺失率为16．95％（40／236）：非梗阻性无精症患者存在13例AZFc缺失，6例AZFb＋C缺失，2例AZFa缺失，1例AZFb缺失。严重少精子症患者存在17例AZFc缺失，1例AZFb缺失。未发现AZFa＋b＋e缺失。40例不育个体通过17Y—STR检测在DYS438、DYS439、DYS437、DYS389I、DYS389II、DYS392、DYS385a／b、DYS448基因座发现了无效等位基因。2例AZFa缺失个体具有DYS438、DYS439、DYS437、DYS389I、DYS389II等位基因缺失；2例AZFb缺失个体具有DYS392、DYS385a／b等位基因缺失；30例AZFc缺失个体具有DYS448等位基因缺失；6例AZFb＋C缺失个体具有DYS392、DYS385a／b、DYS448等位基因缺失。在其他男性不育个体中未见Y—STR缺失。结论Y染色体AZF微缺失是无精症、严重少精子症的主要遗传因素，这种缺失造成法医学相关的Y染色体短串联重复基因座缺失，在性侵犯案件中可导致错误的解释。阐明Y-STR在男性不育人群中的异质性在法医DNA鉴定中可以更好地完善Y—STR数据库和提高STR数据的解释能力。

Objective To investigate the characteristics of null allele for 17 Y-chromosomal short tandem repeats （Y-STR） loci in a group of infertile males. Methods Two hundred thirty six infertile males featuring non-obstructive azoospermia and severe oligozoospermia were analyzed with an AmpFISTR YfilerTM kit. Deletions of azoospermia factor （AZF） fragments were confirmed with Y chromosome sequence-tagged sites （STSs） analysis using modified multiplex PCR. Results The overall prevalence of AZF microdeletions was 16.95% （40/236）. In the non-obstructive azoospermia group, 13 cases had AZFc deletion, 6 cases had AZFb ＋ c deletion, 2 cases had AZFa deletion, 1 case had AZFb deletion. In the severe oligozoospermia group, 17 cases had AZFc deletion and 1 had AZFh deletion. No AZFa＋b＋cdeletion was detected. Forty cases showed null alleles by scanning of the 17 STR loci. Deletions of DYS438, DYS439, DYS437, DYS389I and DYS389II were found in the 2 cases with AZFa deletion. In patients with AZFb deletion, DYS392 and DYS385a/b were found deleted. Deletions of DYS448 were detected in all of the 30 cases with AZFc deletion. Deletions of DYS392, DYS385a/b, and DYS448 were found in 6 cases with AZFb ~ c deletion. Conclusion Deletions of the Y chromosome AZF regions are associated with azoospermia and severe oligozoospermia. Null allele due to complete absence of AZFa, AZFb and AZFc regions may lead to misinterpretation in the sexual assault cases. Revealing the locus heterogeneity in male infertility population can enrich the Y-STR database and facilitate interpretation STR data in forensic DNA testing.