Multicolor fluorescence in situ hybridization analysis of meiotic chromosome segregation in a 47,XYY male and a review of the literature

Shi, Qinghua; Martin, Renée H.

doi:10.1002/1096-8628(20000703)93:1<40::aid-ajmg7>3.0.co;2-k

Cited by 57 publications

(33 citation statements)

References 33 publications

(46 reference statements)

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“…Results from this larger sperm sample suggested that the additional chromosome is eliminated during spermatogenesis in the majority of cells, but that there may be a small but significant increase in the frequency of aneuploid sperm in these men. A recent study of another 47,XYY male in our laboratory yielded similar results, with a small but significant increase in the frequency of sex chromosomal aneuploidy (0.6%; Shi and Martin 2000). Twelve other 47,XYY males have been studied by FISH analysis with a frequency of sex chromosomal aneuploidy ranging from 0.3% to 15% (reviewed by Shi and Martin 2000).…”

Section: Introductionsupporting

confidence: 70%

Recombination in the pseudoautosomal region in a 47,XYY male

Martin

Shi

Field³

2001

Human Genetics

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Males with a 47,XYY karyotype generally have chromosomally normal children, despite the high theoretical risk of aneuploidy. Studies of sperm karyotypes or FISH analysis of sperm have demonstrated that the majority of sperm are chromosomally normal in 47,XYY men. There have been a number of meiotic studies of XYY males attempting to determine whether the additional Y chromosome is eliminated during spermatogenesis, with conflicting results regarding the pairing of the sex chromosomes and the presence of an additional Y. We analyzed recombination in the pseudoautosomal region of the XY bivalent to determine whether this is perturbed in a 47,XYY male. A recombination frequency similar to normal 46,XY men would indicate normal pairing within the XY bivalent, whereas a significantly altered frequency would suggest other types of pairing such as a YY bivalent or an XYY trivalent. Two DNA markers, STS/STS pseudogene and DXYS15, were typed in sperm from a heterozygous 47,XYY male. Individual sperm (23,X or Y) were isolated into PCR tubes using a FACStarPlus flow cytometer. Hemi-nested PCR analysis of the two DNA markers was performed to determine the frequency of recombination. A total of 108 sperm was typed with a 38% recombination frequency between the two DNA markers. This is very similar to the frequency of 38.3% that we have observed in 329 sperm from a normal 46,XY male. Thus our results suggest that XY pairing and recombination occur normally in this 47,XYY male. This could occur by the production of an XY bivalent and Y univalent (which is then lost in most cells) or by loss of the additional Y chromosome in some primitive germ cells or spermatogonia and a proliferative advantage of the normal XY cells.

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Section: Introductionsupporting

confidence: 70%

Recombination in the pseudoautosomal region in a 47,XYY male

Martin

Shi

Field³

2001

Human Genetics

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“…However, a high incidence of sex chromosomal aneuploidies has been observed repeatedly in sperm samples also when the patient´s sperm sample had a low morphological quality and the karyotype in lymphocytes was normal [27][28][29][30][31][32][33][34]. This is because paternal nondisjunction of the meiotic chromosomes includes much more the sex chromosomes (X and Y) than the autosomes, whereas aneuploidies of chromosome 13, 16, 18, 21 occur more frequently by maternal errors during the first and second meiotic division of the maturing oocyte [35].…”

Section: Fig (2)mentioning

confidence: 98%

“…However, all chromosome abnormalities are generally counter-selected by the meiotic segregation mechanisms [26], and translocation chromosomes are expected with a variable frequency in the postmeiotic germ cells. Robertsonian translocation chromosomes were found with a frequency between 3-27% for an unbalanced karyotype in postmeiotic germ cells by FISH and karyotype sperm analyses [32]. Therefore, although there is a general risk for an unbalanced karyotype in the patientsó ffspring, its individual frequency can only be identified by FISH in the germ cells of the patient directly.…”

Section: Fig (2)mentioning

confidence: 99%

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Vogt¹

2004

CPD

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Genetic lesions causing human male infertility are manifold. Besides gross chromosomal aneuploidies and rearrangements, microdeletions and single gene defects can interfere with male fertility. Male fertility is not only dependent on genes controlling the male germ line but also on genes of the networks functional for male gonad development and male somatic development, respectively. It is popular to unravel these netweorks with mouse gene knock-out mutants displaying reproductive defects. However, substantial arguments can be given for more functional studies directly on the human genes, because multiple reproductive proteins evolve quickly most likely for adopting to the specific needs of the species class. Prominent examples are mutations of the FSHR gene causing different pathologies in mouse and human and the DAZ gene family not found in the mouse genome but in the human genome with an essential male fertility function. Therefore this review is focussed on a comprehensive overview of human genes known with mutations causing male infertility (AR; AZF gene families; CFTR, DM-1, DNAH gene family, FGFR1, FSHR, INSL3, KAL-1, LGR8-GREAT, LHR, POLG). Then some human genes are described well recognised as functional in spermatogenesis and male fertility although gene specific mutations causing infertility were not yet identified (CREM, CDY1, DAZL1, PHGPx, PRM-1, PRM-2). They are designated as "spermatogenesis phase marker" or "male fertility index" genes, because they are useful tools for diagnosing the patient´s´ spermatogenesis disruption phase and for predicting the presence and quality of his mature sperms. Current therapeutic protocols for human male infertility do usually not cure the specific gene defect but try to bypass it using Artificial Reproductive Technology (ART). Putative imprinting defects in the early embryo probably associated with the used ART protocol and an increase of chromosome abnormalities in the ART offspring now strongly asks for a significant improvement of this outcome requesting urgently more basic research on the genes functioning in the human male germ line and during early human embryogenesis.

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“…Klinefelter men and mice are usually sterile with a block occurring before meiosis, during the early spermatogonial divisions (Ferguson-Smith 1959;Mroz et al 1999;Lue et al 2001). For Double Y syndrome men, the reproductive outlook varies; the extra Y chromosome is often lost during the early spermatogonial stages and this generates XY (euploid) cell lines that can complete spermatogenesis and support fertility (Chandley 1997;Shi and Martin 2000). In XYY men and mice in which XY cell lines do not arise, infertility results, with germ cell losses occurring during pachytene and the meiotic divisions (Speed et al 1991;Solari and Rey Valzacchi 1997;Mahadevaiah et al 2000;Rodriguez et al 2000).…”

Section: Overview Of Sex Chromosome Infertilitymentioning

confidence: 99%

Function of the Sex Chromosomes in Mammalian Fertility

Heard

Turner²

2011

Cold Spring Harbor Perspectives in Biology

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The sex chromosomes play a highly specialized role in germ cell development in mammals, being enriched in genes expressed in the testis and ovary. Sex chromosome abnormalities (e.g., Klinefelter [XXY] and Turner [XO] syndrome) constitute the largest class of chromosome abnormalities and the commonest genetic cause of infertility in humans. Understanding how sex-gene expression is regulated is therefore critical to our understanding of human reproduction. Here, we describe how the expression of sex-linked genes varies during germ cell development; in females, the inactive X chromosome is reactivated before meiosis, whereas in males the X and Y chromosomes are inactivated at this stage. We discuss the epigenetics of sex chromosome inactivation and how this process has influenced the gene content of the mammalian X and Y chromosomes. We also present working models for how perturbations in sex chromosome inactivation or reactivation result in subfertility in the major classes of sex chromosome abnormalities.T he evolution of sex chromosomes from a pair of autosomes is clearly advantageous to species in enabling sexual reproduction and the genetic fitness that results, but also necessitates the coevolution of strategies to deal with unique situations that arise. These include the lack of homology between the X and Y chromosomes in the male germline in which autosomal homologs must pair and the imbalance in Xlinked gene dosage between males and females. In mammals, this sex chromosome imbalance is dealt with by inactivating one of the two X chromosomes during early female development. In the female germline, the inactive X chromosome is reactivated before meiosis. In the male germline, the X and Y chromosomes undergo meiotic inactivation that is linked to their unique unpaired status. This is a conserved process and has important implications for the evolution of sex chromosome gene content. In this article, we will cover these different aspects of sex chromosome behavior and function in mammals, including the role of sex chromosomes in sex determination and the behavior of the sex chromosomes during gametogenetesis, particularly in the male germline.

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Multicolor fluorescence in situ hybridization analysis of meiotic chromosome segregation in a 47,XYY male and a review of the literature

Cited by 57 publications

References 33 publications

Recombination in the pseudoautosomal region in a 47,XYY male

Recombination in the pseudoautosomal region in a 47,XYY male

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Function of the Sex Chromosomes in Mammalian Fertility

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