Small deletions of the short arm of the Y chromosome in 46,XY females

Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/1986; 83(20):7841-4. DOI: 10.1073/pnas.83.20.7841
Source: PubMed


Structural anomalies of the sex chromosomes provide a means to study the location of genes responsible for sex determination. Recently, a type of sex reversal in humans, the 46,XX male, was shown to result in some cases from translocation of Y chromosome material to the X chromosome. In the present report, another type of sex reversal, the 46,XY female, is shown to result, in two cases, from small deletions of the short arm of the Y chromosome. Prometaphase chromosome analysis showed a 46,X,Yp- karyotype. Several Y chromosome-specific DNA probes were found to be deleted in the two female patients. DNA analysis showed that the two deletions were different but included a common overlapping region likely to be essential for male determination.

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    • "Molecular studies surveying the copy number of Y-specific loci similarly discovered general population duplications and deletions of segments of the chromosome that could be hundreds of kilobases or megabases in size (Jobling et al. 1996; Santos et al. 1998; Saxena et al. 2000; Bosch and Jobling 2003; Fernandes et al. 2004; Repping et al. 2004; Murphy et al. 2007; Balaresque et al. 2008, 2009). Rare pathological CNVs have also been identified , including cytogenetically visible deletions associated with spermatogenetic failure (Tiepolo and Zuffardi 1976) and anomalies of sex determination (Disteche et al. 1986) and three distinct cytogenetically undetectable deletions leading to spermatogenetic failure (Vogt et al. 1996), as well as insertions causing hearing impairment (Wang et al. 2013). In addition, CNVs with milder medically relevant effects have been identified: the gr/gr deletion in the AZFc region of Yq (Repping et al. 2003; Machev et al. 2004) and low TSPY copy number (Giachini et al. 2009), which both slightly increase the risk of spermatogenetic failure, while deletions that remove AMELY have no apparent phenotypic consequences, but confound DNA-based sex tests in forensic analyses (Santos et al. 1998). "
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    ABSTRACT: We have assessed copy number variation (CNV) in the male-specific part of the human Y chromosome discovered by array comparative genomic hybridization (array-CGH) in 411 apparently healthy UK males, and validated the findings using SNP genotype intensity data available for 149 of them. After manual curation taking account of the complex duplicated structure of Y-chromosomal sequences, we discovered 22 curated CNV events considered validated or likely, mean 0.93 (range 0–4) per individual. 16 of these were novel. Curated CNV events ranged in size from <1 kb to >3 Mb, and in frequency from 1/411 to 107/411. Of the 24 protein-coding genes or gene families tested, nine showed CNV. These included a large duplication encompassing the AMELY and TBL1Y genes that probably has no phenotypic effect, partial deletions of the TSPY cluster and AZFc region that may influence spermatogenesis, and other variants with unknown functional implications, including abundant variation in the number of RBMY genes and/or pseudogenes, and a novel complex duplication of two segments overlapping the AZFa region and including the 3′ end of the UTY gene. Electronic supplementary material The online version of this article (doi:10.1007/s00439-015-1562-5) contains supplementary material, which is available to authorized users.
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    • "Germ cell tumors (GCT) are more common in whom the Y-chromosome retains the normally intense florescence of distal Yq. Gonadal dysgenesis is due to the presence of Y-chromosome lacking the male determining region (SRY).[19] SRY is suggested to be functional in spermatogenesis[20] and is the structural gene for H-Y antigen. "
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    ABSTRACT: We report a 17-year-old girl evaluated for primary amenorrhea. Cytogenetic analysis of the peripheral blood lymphocytes revealed normal autosomes with 46X inv (Y) confirming the diagnosis of Turner's syndrome with Y cell line. Treatment was initiated with conjugated estrogen while recommending bilateral prophylactic oophorectomy to the patient. One year later the patient presented with abdominal mass, biopsy of the specimen following resection confirmed dysgerminoma originating from right ovary with no invasion or metastasis. The literature is reviewed with regard to the various pathogenetic mechanisms proposed for the development of germ cell tumors in ovary, the cytogenetic findings and recommendations to handle such scenario.
    No preview · Article · May 2012
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    • "Generating genetic diversity: recombination mechanisms in AZFc Since the mid 1980s, that polymorphisms in the Yq region later identified as AZFc have been appreciated (Lucotte and Ngo, 1985; Disteche et al., 1986). Yet, a more extensive measure of AZFc genetic diversity in the Y chromosome population was only established in 2006 (Repping et al., 2006). "
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    ABSTRACT: The three azoospermia factor (AZF) regions of the Y chromosome represent genomic niches for spermatogenesis genes. Yet, the most distal region, AZFc, is a major generator of large-scale variation in the human genome. Determining to what extent this variability affects spermatogenesis is a highly contentious topic in human reproduction. In this review, an extensive characterization of the molecular mechanisms responsible for AZFc genotypical variation is undertaken. Such data are complemented with the assessment of the clinical consequences for male fertility imputable to the different AZFc variants. For this, a critical re-evaluation of 23 association studies was performed in order to extract unifying conclusions by curtailing methodological heterogeneities. Intrachromosomal homologous recombination mechanisms, either crossover or non-crossover based, are the main drivers for AZFc genetic diversity. In particular, rearrangements affecting gene dosage are the most likely to introduce phenotypical disruptions in the spermatogenic profile. In the specific cases of partial AZFc deletions, both the actual existence and the severity of the spermatogenic defect are dependent on the evolutionary background of the Y chromosome. AZFc is one of the most genetically dynamic regions in the human genome. This property may serve as counter against the genetic degeneracy associated with the lack of a meiotic partner. However, such strategy comes at a price: some rearrangements represent a risk factor or a de-facto causative agent of spermatogenic disruption. Interestingly, this precarious balance is modulated, among other yet unknown factors, by the evolutionary history of the Y chromosome.
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