男性不育与Y染色体

目的：观察精子数目异常与小Y染色体及内分泌性腺激素水平。方法：对262名少精及无精症患者检测染色体,并对其中11例小Y染色体及随机抽取的15例Y染色体正常的患者运用磁性分离酶免疫测定法分别检测性腺激素。结果：小Y染色体检出率为4.19％（11／262）,其内分泌性腺激素均呈高卵泡刺激素、高黄体生成素和低睾酮水平,与Y染色体正常的无精及少精症患者相比较．差异有显著性（P〈0．05）。而小Y染色体不同精子数组各内分泌性腺激素比较,差异无显著性（P〉0．05）。结论：精子数目畀常可能与小Y染色体有关,小Y染色体基因改变可能是导致其内分泌性腺激素的变化因素。     

无精和严重少精症患者的遗传缺陷分析——-附2例世界首报染色体异常核型

对217例无精和严重少精症患者外周血淋巴细胞染色体核型进行分析,并采用聚合酶链反应对7例Y染色体结构异常患者的AZFc区进行检测。发现187例无精症患者中检出异常核型77例（41.18%）（其中46,XY,t(6;14)(p21;p13),46,XY,t(8;12)(p21;q24)为世界首报核型）,主要涉及染色体异常（数目异常和结构异常）;染色体异态（Y染色体异态和9号染色体臂间倒位）及46,XX性反转;30例严重少精症患者中检出异常核型4例（13.33%）（结构异常和46,XX性反转）。由此可见,性染色体数目和结构异常是精子发生障碍的主要原因,其次常染色体的某些断裂点也可能影响精子发生。AZFc区的缺失与否与精子发生也有直接关系。     

Y染色体单倍群与西南地区男性生精障碍的相关性

男性不育中, 原发无精、少精是最为重要的因素之一, 核型异常和无精子症因子(Azoospermia factor, AZF)微缺失能解释部分原发无精、少精的原因, 然而还有许多致病因素尚不清楚。Y染色体作为男性特有的染色体, 与男性生殖系统的正常功能密切相关。文章主要对Y染色体单倍群这一分子遗传背景与男性原发无精、严重少精症之间是否存在相关性进行探讨, 为进一步探索原发无精、严重少精症的遗传学致病原因提供依据和可行的方向。采集265名生精障碍患者(原发无精症患者193名, 原发严重少精症患者72名)以及193名正常男性样本的外周血, 进行核型分析和AZF缺失分析, 以排除有此两类异常的样本。将经过筛选的样本进行Y染色体单倍群分析, 并对其单倍群分布情况进行统计分析。分析显示, 生精障碍组和对照组分别在D1*、F*、K*、N1*和O3* 上有显著性差异(P=0.032, 0.022, 0.009, 0.009, 0.017, <0.05)。Y染色体单倍群, 这一Y染色体遗传背景与男性原发生精障碍的发生有相关性。     

中国无精症、严重寡精症患者的染色体异常和Y染色体微缺失

染色体异常和Y染色体微缺失被认为是两个白种人群中常见的生精障碍相关遗传因素。为了解中国无精症、严重寡精症患者中的染色体异常和Y染色体微缺失,运用染色体G显带技术,在358个原发无精症（256人）和严重寡精症（102人）不育患者中进行染色体核型分析;同时运用多重PCR技术,在核型正常的患者和100个正常生育男性中,对Y染色体AZF区微缺失进行筛查。在358个患者中,39人（10．9％）发现有染色体异常,Klinefelter（47,XYY）最为常见。无精症患者性染色体异常频率明显高于严重寡精症患者（12．1％VS1％）。在319个核型正常的患者中,46（14．4％）发现有AZF区微缺失,无精症和寡精症患者中Y染色体微缺失频率分别为15％和13．1％,AZFc区的微缺失最为常见,AZFa区的微缺失只见于无精症患者,正常生育男性中未发现AZF区的微缺失。结果显示,在中国无精症、严重寡精症患者中,大约25％的患者有染色体异常或Y染色体AZF区微缺失,提示这两种遗传异常是中国人群生精障碍的重要相关遗传病因,有必要在男性不育的诊断以及利用细胞浆内精子注射技术进行辅助生育时,对患者的这些遗传异常进行筛查。     

无精子症和严重少精子症患者Y染色体微缺失研究

目的：研究Y染色体微缺失与男性不育的关系。方法：采用多重PCR技术,研究正常男性、无精子症和严重少精子症男性不育患者Y染色体无精子因子（AZF）区域3个序列标志位点（STS）的缺失情况。结果：在93例无精子症或严重少精子症患者中,15例有Y染色体微缺失,缺失率为16%。其中,42例无精子症患者中,6例为AZFc区SY255位点缺失,2例为AZFb区SY134位点缺失;51例严重少精子症患者中,7例为AZFc区SY255位点缺失。40例正常男性无Y染色体微缺失。结论：多重PCR技术是简便而有效的对男性不育患者进行Y染色体微缺失筛查的方法;Y染色体微缺失是造成男性不育的一个重要原因,对男性不育患者进行辅助生育技术治疗前应常规进行Y染色体微缺失的检测。     

癌基因与性腺功能

癌基因存在于正常的卵巢和睾丸中,在卵巢的生卵,睾丸的生精过程及两者的内分泌功能中均起重要作用。促性腺激素,甾体激素和多种生长因子对性腺功能的高控可能与癌基因的表达有关。     

用双色荧光愿位杂交和PCR技术鉴定无精症患者标记染色体的来源

目的：为了研究无精症患标记染色体的来源,对无精症患进行明确的遗传学诊断。方法：应用双色FISH技术和PCR技术对2例无精症患进行分子细胞遗传学和分子遗传学检测。结果：确定了两例特发性无精症患的标记染色体均来源于Y染色体,其核型为46,X,ishdel(Y)(q11)(DYZ3 ,DXZ1-)。结论：FISH技术结合PCR技术,是鉴定标记染色体来源的又一非常重要方法,对于无精症患在进行胞质内单精子注射（ICSI）或其它治疗之前,完成遗传咨询和明确的遗传学诊断也是特别必须的。     

QF-PCR筛查男性不育患者Y染色体无精子症因子微缺失

为评估定量荧光PCR(Quantitative fluorescent polymerase chain reaction, QF-PCR)技术在快速筛查无精子症因子(Azoospermia factor, AZF)微缺失中的应用, 文章对1218例非梗阻性无精子症、少精子症的男性不育患者, 采用多重QF-PCR结合毛细管电泳技术, 检测Y染色体长臂AZF区9个序列标签位点(Sequence tagged site, STS)以及性染色体短臂的AMEL(Amelogenin)和SRY(Sex-determining region of Y chromosome)位点, 辅以常规染色体G显带方法进行核型分析。结果显示, 1218例患者中105例可见AZF区微缺失(8.62%), 其中AZFc区缺失(67.62%)最常见, 其次为AZFb,c区缺失(20.95%); AZFb区缺失(7.62%)和AZFa区缺失(3.81%)则较少见; 另有5例患者为AZFa,b,c区缺失合并AMEL-Y缺失, 提示可能缺少Y染色体, 经核型分析验证为46,XX(性反转)。105例AZF区微缺失患者的染色体核型分析显示染色体异常16例, 其中“Yqh-”12例。根据AMEL-X/AMEL-Y比值, 可见1218例患者中86例可能存在性染色体异常, 经核型分析验证, 68例为性染色体非整倍体。多重QF-PCR技术, 一个反应即能检测样本的多个位点, 并可提示性染色体是否存在异常, 有助于男性不育患者尽早明确病因, 也为后续的检查和治疗提供依据。     

棕色田鼠XO雌体的减数分裂

采用诱导卵泡发育、卵母细胞培养、制备减数分裂染色体标本等技术 ,对棕色田鼠两种雌体 (XO、XX)的减数分裂进行了比较研究。研究结果表明 :棕色田鼠XO和XX雌体在表型和内外生殖器结构上无差异 ;在用孕马血清促性腺激素刺激XO雌体和XX雌体后 ,两者卵巢上的有腔卵泡数目相近 ;两者产生的卵母细胞数目、生发泡破裂数目以及第一极体排放数目 ,统计学分析差异都不显著。同时表明XO雌体的减数分裂过程正常 ,能得到卵母细胞中期Ⅱ分裂相。据此我们认为 :雌体 (XO)与雌体 (XX)的卵巢功能都正常 ,两者的卵母细胞均具有较强的成熟能力且无差异。因此 ,棕色田鼠XO个体是核型异常、育性正常的雌体。另外 ,具有三种遗传性别的棕色田鼠可能是处于XX/XY与XO/XY性别决定系统进化途径的中间类型 ,其性别决定系统仍处于变化之中     

用团头鲂精子诱导金鱼雌核发育研究

本文用紫外灭活的团头鲂(Megalobrama amblycephala)精子激活金鱼 (Carassius auratus Goldfish)卵子,用0－4℃冷水冷休克处理卵子使其染色体加倍,得到成活的雌核发育金鱼。使用与金鱼不同亚科的团头鲂精子做为激活源能极大提高雌核发育后代的鉴定效率,只需依据外形特征、染色体数目和性腺发育程度,就能容易地将雌核发育金鱼和与团头鲂杂交后代区分开。雌核发育金鱼有两种体色不同的后代,但都为双尾,体形似金鱼,染色体数目为2n=100,全雌,性腺发育正常;而杂交后代为单尾,体形似鲫鱼,染色体数目为3n=124,性腺发育滞后。本实验为证明金鱼的性别决定方式为XX/XY型提供了细胞遗传学证据。得到两种体色皆不同于母本体色的后代,体色不同可能是基因座位纯化导致后代性状分化,也可能是异精效应导致。     

Screening for microdeletions in human Y chromosome--AZF candidate genes and male infertility

About 30% of couple infertilities are of male origin, some of them caused by genetic abnormalities of the Y chromosome. Deletions in AZF region can cause severe spermatogenic defects ranging from non-obstructive azoospermia to oligospermia. The intracytoplasmatic sperm injection technique (ICSI) is rapidly becoming a versatile procedure for human assisted reproduction in case of male infertility. The use of ICSI allows Y chromosome defects to be passed from father. The goal of our study is to evaluate the frequency of microdeletions in the long arm of Y chromosome, within the AZF regions, in these cases of infertilities, using molecular genetics techniques. Thirty infertile men with azoospermia or oligozoospermia, determined by spermogram, were studied after exclusion of patients with endocrine or obstructive causes of infertility. Peripheral blood DNA was extracted from each patient, then amplified by multiplex PCR with STS genomic markers from the Y chromosome AZF zones. Each case was checked by multiplex PCR through coamplification with the SRY marker. Three men with microdeletions of the long arm of the Y chromosome were diagnosed among the 30 patients, corresponding to a proportion of 10%. The relatively high proportion of microdeletions found in our population suggest the need for strict patient selection to avoid unnecessary screening for long arm Y chromosome microdeletions. The molecular diagnostics was performed according to the current European Academy of Andrology laboratory guidelines for molecular diagnosis of Y chromosomal microdeletions.     

Sex chromosomes and human growth

Studies on tooth crown size and structure of individuals with various sex chromosome anomalies and their normal male and female relatives have demonstrated differential direct effects on growth of genes on the human X and Y chromosomes. The Y chromosome promotes growth of both tooth enamel and dentin, whereas the effect of the X chromosome on tooth growth seems to be restricted to enamel formation. Enamel growth is decisively influenced by cell secretory function and dentin growth by cell proliferation. It is suggested that these differential effects of the X and Y chromosomes on growth explain the expression of sexual dimorphism in various somatic features, such as the size, shape and number of teeth, and, under the assumption of genetic pleiotropy, torus mandibularis, statural growth, and sex ratio. Future questions concern, among other topics, the Y chromosome and the mineralization process, concentric control of enamel and dentin growth, and gene expression. Received: 11 March 1997 / Accepted: 10 June 1997     

Le risque chromosomique pour un patient porteur d'une translocation t(X;2) concerne non seulement la translocation mais aussi la ségrégation XY

In men, translocations involving sex chromosomes usually result in azoospermia or sometimes oligospermia. We report the case of a man with oligospermia with a 46,Y,t(X;2)(p21;p25.3) translocation and the specific modalities of management of the couple before ICSI. After genetic counselling, we proposed spermatozoa chromosomal analysis using FISH to evaluate the mode of segregation of the translocation and the risk for the embryo and descendants. This study showed that 34% of spermatozoa were normal or balanced for the chromosomes studied, and 66% of spermatozoa presented a chromosome imbalance related to the translocation and/or involving X and Y chromosome non-disjuction. In view of this result, we decided to perform another FISH analysis to define the increased risk related to the non-disjunction of X and Y chromosomes. Only 60% of 1,000 spermatozoa were normal for X and Y. The chromosome risk for the offspring is not limited to the translocation, as the risk of Klinefelter and Turner syndrome is also increased. In view of these results and the woman's age (42 years old), we advised the couple against ICSI at another genetic counselling session. This case illustrates the value of spermatozoa FISH analysis to evaluate the consequences of a translocation on spermatogenesis. The study should not be limited to the translocation alone, but should also evaluate anomalies of non-disjunction of sex chromosomes that are frequent during normal spermatogenesis, but the risk increases in the case of translocations, especially involving the sex chromosomes.     

Incidence of numerical chromosome aberrations in meningioma tumors as revealed by fluorescence in situ hybridization using 10 chromosome-specific probes

OBJECTIVE: Although information on the cytogenetic characteristics of meningioma tumors has accumulated progressively over the past few decades, information on the genetic heterogeneity of meningiomas is still scanty. The aim of the present study was to analyze by interphase fluorescence in situ hybridization (FISH) the incidence of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in a group of 70 consecutive meningioma tumors. Another goal was to establish the potential associations among the altered chromosomes, as a way to assess both intertumoral and intratumoral heterogeneity. METHODS: For the purpose of the study, 70 patients diagnosed with meningioma were analyzed. Interphase FISH for the detection of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y was applied to fresh tumor samples from each of the patients studied. RESULTS: The overall incidence of numerical abnormalities was 76%. Chromosome Y in males and chromosome 22 in the whole series were the most common abnormalities (46% and 61%, respectively). Despite the finding that monosomy of chromosome 22/22q(-) deletions are the most frequent individual abnormality (53%), we have observed that chromosome gains are significantly more common than chromosome losses (60% versus 40%). Chromosome gains corresponded to abnormalities of chromosomes 1 (27%), 9 (25%), 10 (23%), 11 (22%), 14 (33%), 15 (22%), 17 (23%), and X in females (35%) and males (23%) whereas chromosome losses apart from chromosome 22 frequently involved chromosomes 14 (19%), X in males (23%), and Y in males (32%). Although an association was found among most gained chromosomes on one side and chromosome losses on the other side, different association patterns were observed. Furthermore, in the latter group, monosomy 22/22q(-) was associated with monosomy X in females and monosomy 14/14q(-) was associated with nulisomy Y in males. In addition, chromosome losses usually involved a large proportion of the tumor cells whereas chromosome gains were restricted to small tumor cell clones, including tetraploid cells. CONCLUSIONS: Our results show that meningiomas are genetically heterogeneous tumors that display different patterns of numerical chromosome changes, as assessed by interphase FISH.     

615小鼠染色体组型与G带带型分析

目的建立615小鼠标准染色体组型与G带染色体核型,提供可靠的细胞遗传学背景资料。方法成年615小鼠8只,雌雄各半,提取骨髓细胞,制片,镜检。确立615小鼠体细胞染色体数目。选择10个典型细胞测量染色体基本数据。G带染色。结果615小鼠的染色体数目为40条,XX为雌性,XY为雄性。所有染色体均为中部着丝点。X染色体相对长度仅次于第1对染色体,Y染色体的相对长度在第4对染色体和第5对染色体之间。G显带条数与小鼠有很大差异,接近于大鼠。结论615小鼠的核型为2n=40=2×19m＋（x）m＋（y）m,G显带共262条。     

Size variation and orientation of the human Y chromosome

Summary The material consists of 84 metaphase plates from 17 individuals with clearly distinguishable Y chromosomes. The plates were obtained from leucocyte cultures. In making the preparations, exactly the same procedure was employed in all cases, including among other things, air-drying and light flaming.It was found that the size of the Y chromosome is subject to interindividual variation. The size of the Y chromosome has been expressed in relation to the mean length of the other small acrocentric chromosomes. The chromosomes have been tentatively classified into the following main groups:1. Y/G = 1.8; 2. Y/G =1.5; 3. Y/G is somewhat larger than G or 1.1, and 4. Y/G equals the mean of the small acrocentric chromosomes, or Y/G = 1. In the long Y chromosome two secondary constrictions have been observed.The location of the Y chromosome has been determined as peripheral or non-peripheral. The proband material has been divided into three main groups. The first comprises the individuals with a large Y chromosome (Y/G = 1.8). The second group includes individuals showing Down's syndrome and having 47 chromosomes, and the third comprises individuals with 46 chromosomes and possessing a Y/G sized 1 to 1.5. Preferential peripheral location of the Y chromosome has not been statistically verified in any one of these groups.