Features of constitutive gr/gr deletion in a Japanese population
Features of constitutive gr/gr deletion in a Japanese population
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日本人群中结构性 gr/gr 缺失的特征
DOI：
10.1093/humrep/deq191
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发表时间：
2010
期刊：
影响因子：
6.1
通讯作者：
Namiki M
中科院分区：
文献类型：
--
作者：
Sin HS;Koh E;Shigehara K;Sugimoto K;Maeda Y;Yoshida A;Kyono K;Namiki M
男性不育与gr/gr缺失（去除Y染色体的多个基因）之间的关系因国家和人群而异。本研究的目的是探讨gr/gr缺失和生精表型之间的关联在生育和不育的日本men. METHODS的主题进行了筛选序列标记位点（STS）分析，以检测gr/gr缺失，和单倍型群分配使用8个高度信息化的标记。共有395名不育男性和377名生育男性（对照组）参与了我们的研究。在772名受试者中，260名个体携带确认的gr/gr缺失，并用于进一步分析缺失亚型和基因拷贝数，特别是CDY 1和DAZ拷贝的丢失和获得。这260名受试者被分为对照组（n= 131），均为正常精子，不育组（n= 129），89例不育受试者表现为无精子症（无精子）和40例表现为少精子症在所有受试者中有33.7%（260/772）的人存在gr/gr缺失，缺失在单倍型D中广泛存在（86.2%）。不育组和对照组的gr/gr缺失频率无显著差异。gr/gr缺失亚型在单倍群中的分布不是随机的，96.9%（217/224）的单倍群个体缺失CDY 1a + DAZ 1/2基因，而O家系存在多种gr/gr缺失类型。CD Y 1a + DAZ 1/2的缺失与单倍型D的生精障碍无关（P= 0.33）。需要进一步的研究来确定AZF区外的Y连锁代偿因子是否可以抵消D谱系中gr/gr缺失的致病作用。
BACKGROUNDThe relationship between male infertility and gr/gr deletions that remove multiple genes of the Y chromosome varies among countries and populations. The aim of this study was to investigate the association between gr/gr deletions and spermatogenic phenotype in fertile and infertile Japanese men.METHODSThe subjects were screened by sequence-tagged site (STS) analysis to detect gr/gr deletions, and haplogroups were assigned using eight highly informative markers. In total, 395 infertile men and 377 fertile men (controls) participated in our study. Of the 772 subjects, 260 individuals carried confirmed gr/gr deletions and were used in further analysis of deletion subtype and gene copy number, specifically loss and gain of CDY1 and DAZ copies. These 260 subjects were divided into a control group (n= 131) all with normozoospermia, and an infertile group (n= 129) with 89 infertile subjects exhibiting azoospermia (absence of sperm) and 40 exhibiting oligozoospermia (reduced sperm concentration).RESULTSThere were gr/gr deletions in 33.7% (260/772) of all subjects and the deletions were widespread in haplogroup D (86.2%). There were no significant differences in the frequency of gr/gr deletions between the infertile and control groups. The gr/gr deletion subtypes were not distributed randomly among haplogroups; theCDY1a+ DAZ1/2genes were deleted in 96.9% (217/224) of haplogroup D individuals, whereas the O lineage had a variety of gr/gr deletion types. The loss ofCDY1a+ DAZ1/2was not associated with spermatogenic impairment in haplogroup D (P= 0.33).CONCLUSIONSTaken together, gr/gr deletions in haplogroup D occur constitutively, are associated with the loss ofCDY1a + DAZ1/2and are phenotypically neutral. Further studies are needed to establish whether Y-linked compensatory factors outside theAZFcregion can counteract the pathogenic effect of a gr/gr deletion in the D lineage.