Y Chromosome and Mitochondrial DNA Variation in Lithuanians

The genetic composition of the Lithuanian population was investigated by analysing mitochondrial DNA hypervariable region 1, RFLP polymorphisms and Y chromosomal biallelic and STR markers in six ethnolinguistic groups of Lithuanians, to address questions about the origin and genetic structure of the present day population. There were no significant genetic differences among ethnolinguistic groups, and an analysis of molecular variance confirmed the homogeneity of the Lithuanian population. MtDNA diversity revealed that Lithuanians are close to both Slavic (Indo‐European) and Finno‐Ugric speaking populations of Northern and Eastern Europe. Y‐chromosome SNP haplogroup analysis showed Lithuanians to be closest to Latvians and Estonians. Significant differences between Lithuanian and Estonian Y chromosome STR haplotypes suggested that these populations have had different demographic histories. We suggest that the observed pattern of Y chromosome diversity in Lithuanians may be explained by a population bottleneck associated with Indo‐European contact. Different Y chromosome STR distributions in Lithuanians and Estonians might be explained by different origins or, alternatively, be the result of some period of isolation and genetic drift after the population split.     

Localization of 24 cosmid clones on the human Y chromosome

Summary Twenty-four novel cosmid clones were cloned and mapped on the human Y chromosome using a panel consisting of DNA from seven individuals each having a different segment of the Y chromosome. Eight were assigned to the short arm, 15 to the long arm and 1 to the both short and long arms.     

Mutation rates at Y chromosome specific microsatellites

A collaborative work was carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG) to estimate Y-STR mutation rates. Seventeen Y chromosome STR loci (DYS19, DYS385, DYS389I and II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS460, DYS461, DYS635 [GATA C4], GATA H4, and GATA A10) were analyzed in a sample of 3,026 father/son pairs. Among 27,029 allele transfers, 54 mutations were observed, with an overall mutation rate across the 17 loci of 1.998 x 10(-3) (95% CI, 1.501 x 10(-3) to 2.606 x 10(-3)). With just one exception, all of the mutations were single-step, and they were observed only once per gametogenesis. Repeat gains were more frequent than losses, longer alleles were found to be more mutable, and the mutation rate seemed to increase with the father's age. Hum Mutat 26(6), 520-528, 2005. (c) 2005 Wiley-Liss, Inc.     

人类Y染色体微缺失与精子生成障碍的研究进展

本文就人类Y染色体的结构及其与精子生成相关的主要功能基因的研究进展作了综述,重点对AZF区的USP9Y.RBM. DAZ. CDY等基因的缺失与精子生成障碍的关系进行了探讨。为临床实施辅助生育技术治疗前对精子质量的筛查.无精症患者的诊断及遗传咨询提供理论依据。     

TSPY, the Candidate Gonadoblastoma Gene on the Human Y Chromosome, has a Widely Expressed Homologue on the X - Implications for Y Chromosome Evolution

TSPY, a candidate gene for a factor that promotes gonadoblastoma formation (GBY), is a testis-specific multicopy gene family in the male-specific region of the human Y (MSY) chromosome. Although it was originally proposed that male-specific genes on the Y originated from a transposed copy of an autosomal gene (Lahn & Page 1999b), at least two male-specific genes (RBMY and SRY) descended from a formerly recombining X-Y identical gene pair. Here we show that a TSPY homologue with similar gene structure lies in conserved positions, close to SMCX, on the X chromosome in human (TSPX ) and mouse (Tspx). TSPX is widely expressed and subject to X inactivation. TSPX and TSPY therefore evolved from an identical gene pair on the original mammalian sex chromosomes. This supports the hypothesis that even male-specific genes on the Y chromosome may have their origin in ubiquitously expressed genes on the X. It also strengthens the case for TSPY as a candidate for GBY, since independent functional studies link TSPX to cell cycle regulation.     

人类Y染色体STR位点在群体遗传学中的应用

Y染色体STR位点在群体遗传学研究中是线粒体DNA的有益补充,是研究男性进化历史的绝好工具.本文介绍了Y-STR位点的遗传学特点以及多态性研究进展;总结了应用Y-STR位点进行群体遗传学研究的常用方法:直接比较法、分子变异分析构建系统树、分层聚类分析、主成分分析等;同时指出了应用Y-STR位点用于群体遗传学研究存在的问题和今后的发展方向.     

Dynamic nature of the proximal AZFc region of the human Y chromosome: multiple independent deletion and duplication events revealed by microsatellite analysis

The human Y chromosome shows frequent structural variants, some of which are selectively neutral, while others cause impaired fertility due to the loss of spermatogenic genes. The large-scale use of multiple Y-chromosomal microsatellites in forensic and population genetic studies can reveal such variants, through the absence or duplication of specific markers in haplotypes. We describe Y chromosomes in apparently normal males carrying null and duplicated alleles at the microsatellite DYS448, which lies in the proximal part of the azoospermia factor c (AZFc) region, important in spermatogenesis, and made up of "ampliconic" repeats that act as substrates for nonallelic homologous recombination (NAHR). Physical mapping in 26 DYS448 deletion chromosomes reveals that only three cases belong to a previously described class, representing independent occurrences of an approximately 1.5-Mb deletion mediated by recombination between the b1 and b3 repeat units. The remainder belong to five novel classes; none appears to be mediated through homologous recombination, and all remove some genes, but are likely to be compatible with normal fertility. A combination of deletion analysis with binary-marker and microsatellite haplotyping shows that the 26 deletions represent nine independent events. Nine DYS448 duplication chromosomes can be explained by four independent events. Some lineages have risen to high frequency in particular populations, in particular a deletion within haplogroup (hg) C(*)(xC3a,C3c) found in 18 Asian males. The nonrandom phylogenetic distribution of duplication and deletion events suggests possible structural predisposition to such mutations in hgs C and G.     

Population Structure in the Mediterranean Basin: A Y Chromosome Perspective

The Mediterranean region has been characterised by a number of pre‐historical and historical demographic events whose legacy on the current genetic landscape is still a matter of debate. In order to investigate the degree of population structure across the Mediterranean, we have investigated Y chromosome variation in a large dataset of Mediterranean populations, 11 of which are first described here. Our analyses identify four main clusters in the Mediterranean that can be labelled as North Africa, Arab, Central‐East and West Mediterranean. In particular, Near Eastern samples tend to separate according to the presence of Arab Y chromosome lineages, suggesting that the Arab expansion played a major role in shaping the current genetic structuring within the Fertile Crescent.     

PCR and FISH analysis of a ring Y chromosome

A newborn male infant presented with midshaft hypospadias, chordee, and undescended left testis. Both gonads lacked the tunica albuginea and appeared to be adjacent to structures resembling fallopian tubes. On biopsy, there was marked dysgenesis of both gonads, with a paucity of testicular tubules and foci of ovarian-like stroma. Peripheral blood karyotype was 46,X,mar(Y) [39]/45,X [5]. Right gonadal biopsy material showed the same mosaicism but with a higher proportion of 45,X cells (46%). PCR and FISH analyses with primers/probes from different Yp, Yq, and Ycen loci defined the structure of the marker Y as a probable complex ring with breakpoints in Yq11.21 (very close to the centromere) and in Yp11.32 (the pseudoautosomal region). Based on the phenotype and the laboratory findings, the prognosis given to the patient was for short stature and azoospermia without an increased risk for gonadoblastomas. Am. J. Med. Genet. 69:171–176, 1997. © 1997 Wiley-Liss, Inc.     

Seeing the Wood for the Trees: A Minimal Reference Phylogeny for the Human Y Chromosome

During the last few decades, a wealth of studies dedicated to the human Y chromosome and its DNA variation, in particular Y‐chromosome single‐nucleotide polymorphisms (Y‐SNPs), has led to the construction of a well‐established Y‐chromosome phylogeny. Since the recent advent of new sequencing technologies, the discovery of additional Y‐SNPs is exploding and their continuous incorporation in the phylogenetic tree is leading to an ever higher resolution. However, the large and increasing amount of information included in the “complete” Y‐chromosome phylogeny, which now already includes many thousands of identified Y‐SNPs, can be overwhelming and complicates its understanding as well as the task of selecting suitable markers for genotyping purposes in evolutionary, demographic, anthropological, genealogical, medical, and forensic studies. As a solution, we introduce a concise reference phylogeny whereby we do not aim to provide an exhaustive tree that includes all known Y‐SNPs but, rather, a quite stable reference tree aiming for optimal global discrimination capacity based on a strongly reduced set that includes only the most resolving Y‐SNPs. Furthermore, with this reference tree, we wish to propose a common standard for Y‐marker as well as Y‐haplogroup nomenclature. The current version of our tree is based on a core set of 417 branch‐defining Y‐SNPs and is available online at http://www.phylotree.org/Y .     

一种新型通用引物多重PCR技术可特异性检测Y染色体序列标签位点

目的:建立通用引物多重PCR(UP-M-PCR)技术,检测Y染色体微缺失。方法:选取50例健康男性,针对Y染色体AZFa,AZFb,AZFc和AZFd区15个标签位点(STS),选择15对特异性引物和1对UP,将UP加在特异性引物对的5’端,按扩增片段大小组建4组稳定可靠的UP-M-PCR体系,分析其扩增效率和特异性。结果:UP引入M-PCR对检测体系无影响。UP-M-PCR可特异性扩增AZF区15个STS,且较M-PCR特异性更好,条带更清晰。结论:UP-M-PCR体系较M-PCR操作方便,扩增效率均衡,特异性高,是男性不育患者Y染色体微缺失筛查的新方法。     

Y染色体异常的细胞遗传学研究及其临床效应分析

分析了68例Y染色体异常(除外数目异常)与各种临床表现的相关性。结果 Yp-14例，占20．59％；Yp 2例；占2．94％；Yq-19例，占27．94％；大Y32例，占47．06％。结论 Y染色体异常与不育、精子异常、流产、智力低下等临床效应有关。     

Y染色体AZF微缺失在男性不育患者中的临床研究

目的研究男性不育患者的Y染色体AZF微缺失情况,分析Y染色体AZF微缺失与性激素水平及男性不育之间的关系。方法选取医院2017年1月至2018年7月收治的120例男性不育患者(其中包含98例非梗阻无精子症患者和22例严重少精症患者),和40例同期体检精液参数正常的体检人员作为研究对象,分别设为A组、B组和对照组,对比分析3组受试者的Y染色体AZF微缺失情况以及性激素指标水平。结果120例男性不育患者中共检出16例Y染色体AZF微缺失,A组的缺失率为14.29%,B组为9.09%,对照组未发现缺失,A组的缺失率显著高于对照组(P<0.05)。16例Y染色体AZF微缺失的患者中,共包含12个位点缺失,其中单纯AZFb型、AZFb+c型、AZFc+d型和AZFb+c+d型分别3例、2例、10例和1例;3组的睾酮水平无明显差别(P>0.05),A组的黄体生成素和促卵泡生成素水平显著高于对照组(P<0.05);AZFb+c+d型基因缺失患者的FSH指标水平显著高于无AZF基因缺失和AZFb型、AZFb+c型、AZFc+d型缺失患者(P<0.05)。结论Y染色体AZF基因微缺失可能是影响非梗阻性无精子症的重要因素之一,男性不育症患者的Y染色体AZF微缺失与患者的FSH水平具有密切关系,在临床诊治中,Y染色体AZF基因检测能够为男性不育症诊断提供更加科学的依据。     

In situ fluorescence hybridization of Y translations: cytogenetic analysis using probes Y190 and Y431

Two moderately repetitive DNA probes (Y190 and Y431) and a fluorescent in situ hybridization technique, using a biotin, avidin, anti-avidin system, were employed to investigate a group of patients with Y chromosome abnormalities. In normal male subjects, a bright fluorescent spot could be detected in cells in interphase and on the short arm of the Y chromosome in metaphase spreads. Translocations of DNA fragments of the short arm of the Y chromosome to autosomes 10, 13 and 15 were observed in five patients. In a 45,XX male subject the translocation involved one of the X chromosomes. With this in situ hybridization procedure, bright fluorescent spots were also noticed in uncultured amniotic cells and chorionic cellular elements from male fetuses, thus allowing a rapid and reproducible approach to prenatal fetal sexing.     

Location of the handedness gene on the X and Y chromosomes

Accumulated data from five handedness surveys show that concordance for sex is slightly but reliably higher among siblings of the same handedness than among those of opposite handedness. This is consistent with Crow's theory that the genetic locus for handedness is in an X-Y homologous region of the sex chromosomes. The small size of the effect is predicted from genetic models in which there is a substantial random component underlying phenotypic left handedness. The findings are relevant to the putative role of cerebral asymmetry in the aetiology of psychosis. © 1996 Wiley-Liss, Inc.     

长沙地区大Y染色体核型98例临床效应

目的探讨大Y染色体核型的临床意义。方法常规外周血细胞培养和染色体标本制备,并对染色体核型进行分析。结果98例大Y染色体核型中,其妻曾生育出生缺陷儿者27例,占36%;不明原因不育者22例,占29.3%;其妻有自然流产史者10例,占13.3%;无精症7例,占9.3%;少精症4例,占5.3%;弱精症3例,占4%;23例无临床症状,占23.5%。结论大Y染色体核型可能有一定的临床效应。     

Characterization of an Alphoid Subfamily Located Near P-arm Sequences on Human Chromosome 22

The centromeric heterochromatin of all human chromosomes is composed of tandemly repeated alpha satellite DNA. Here we describe another alphoid subfamily that maps to human chromosome 22 as determined by FISH. The alphoid sequences were isolated from three YAC-clones carrying DNA from the pericentromeric region of the short arm of human chromosome 22 and limited amounts of alphoid DNA. This property enabled us to map the members of the subfamily to the border of the centromeric region and the short arm of the chromosome. The new alphoid subfamily may contribute to the closure of the gap remaining between the centromeric and short-arm maps of human chromosome 22. This revised version was published online in August 2006 with corrections to the Cover Date.     

Presence of Y chromosome sequences and their effect on the phenotype of six patients with Y chromosome anomalies

The extent of Y chromosome material was determined in 6 southern African subjects with sex chromosome anomalies. Four of the subjects were phenotypically female, and 2 were phenotypically male. Molecular and cytogenetic findings were correlated with phenotypic expression. An X;Y translocation was found in both male subjects, and in one female subject. The remaining female subjects were characterized by an isodicentric Y, an isochromosome Yq, and a micromarker of undetermined origin, respectively. The individuals were tested for the presence of a number of Y-specific DNA sequences. Molecular findings were generally compatible with the cytogenetic findings, and also with the phenotypic sex of the patients. All the female subjects had Y material and all but one were negative for the sex determining region of the Y (SRY). The somatic Ullrich-Turner-like findings present in 3 of the females were attributed to either the presence of a 45,X cell line and/or a single copy of Xp. The males both showed X;Y translocations without any detectable loss of Y DNA. Although molecularly very similar, the disparate clinical findings in these 2 subjects could have been accounted for by different X inactivation patterns. © 1995 Wiley-Liss, Inc.     

Chemosensory identity and the Y chromosome

Genes in the extended major histocompatibility complex (MHC) of the mouse (H-2 QaT1a) impart to each mouse an odor that reflects its genetic constitution at this region of chromosome 17. Sensory recognition of these differential odors influences reproductive behavior and evokes neuroendocrine responses critical to the maintenance of pregnancy. To determine whether other parts of the mouse genome contribute to individual odor, and so may similarly exert a selective force on loci other than the MHC, mice differing genetically only in their X and/or Y chromosomes were tested for individuality of scent in the Y-maze system previously employed to investigate MHC-related scent distinctions. It was found that the X and Y chromosomes each confer individuality of scent related to genotype, but differences at the H-2 locus are considerably more salient. Never-theless, chemosensory cues controlled by differences on the Y chromosome could play a role in individual recognition, mate selection, aggressive interactions, and perhaps other aspects of mouse chemosensory behavior.This work was supported in part by Grants CA-39827 and GMCA-30296 from the National Institutes of Health. E.A.B. is an American Cancer Society Research Professor of Cell Surface Immunogenetics.     

Buccal cell FISH and blood PCR-Y detect high rates of X chromosomal mosaicism and Y chromosomal derivatives in patients with Turner syndrome

Turner syndrome (TS) is the result of (partial) X chromosome monosomy. In general, the diagnosis is based on karyotyping of 30 blood lymphocytes. This technique, however, does not rule out tissue mosaicism or low grade mosaicism in the blood. Because of the associated risk of gonadoblastoma, mosaicism is especially important in case this involves a Y chromosome. We investigated different approaches to improve the detection of mosaicisms in 162 adult women with TS (mean age 29.9 ± 10.3). Standard karyotyping identified 75 patients (46.3%) with a non-mosaic monosomy 45,X. Of these 75 patients, 63 underwent additional investigations including FISH on buccal cells with X- and Y-specific probes and PCR-Y on blood. FISH analysis of buccal cells revealed a mosaicism in 19 of the 63 patients (30.2%). In five patients the additional cell lines contained a (derivative) Y chromosome. With sensitive real-time PCR we confirmed the presence of this Y chromosome in blood in three of the five cases. Although Y chromosome material was established in ovarian tissue in two patients, no gonadoblastoma was found. Our results confirm the notion that TS patients with 45,X on conventional karyotyping often have tissue specific mosaicisms, some of which include a Y chromosome. Although further investigations are needed to estimate the risk of gonadoblastoma in patients with Y chromosome material in buccal cells, we conclude that FISH or real-time PCR on buccal cells should be considered in TS patients with 45,X on standard karyotyping.