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Query: UNIPROT:P06889 (Mol)
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Five couples at risk of producing offspring with X-linked recessive disease underwent in vitro fertilisation with a view to preimplantation determination of embryo sex and selective transfer of females. On day three postinsemination, one or two blastomeres were removed by embryo biopsy, and used for dual fluorescent in situ hybridisation with X and Y chromosome-specific DNA probes. In two cases, two female embryos were transferred and one pregnancy, (sex confirmed), is ongoing at 19 weeks. All eight embryos from one couple were of such poor quality that diagnosis was possible in one only. In the remaining two cases no embryos were transferred due to the detection of an abnormal number of X chromosome signals. Investigation of the biopsied embryos that were not transferred revealed evidence of mitotic non-disjunction in one and of complete X monosomy in a second. A surviving fetus with this latter constitution would have developed Turner syndrome and would also have been at high risk of X-linked disease. The use of fluorescent in situ hybridisation rather than the polymerase chain reaction allowed the detection of abnormal copy numbers of X chromosomes thus preventing the transfer of potentially abnormal zygotes.
Hum Mol Genet 1993 Aug
PMID:Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation, (FISH). 840 99

We have determined the orientation of the major centromeric alphoid array on the human Y chromosome. A PCR assay was used to analyse the vector-insert junctions of seven YAC clones previously positioned on two independent Y chromosomes. The orientation is the same at all 10 positions measured. This suggests that the alphoid array is a simple unidirectional repeat throughout and that human centromere structure thus differs from the palindromic organisation found in Schizosaccharomyces pombe.
Hum Mol Genet 1993 Aug
PMID:The major centromeric array of alphoid satellite DNA on the human Y chromosome is non-palindromic. 840 8

The much larger number of cell divisions between zygote and sperm than between zygote and egg, the increased age of fathers of children with new dominant mutations, and the greater evolution rate of pseudogenes of the Y chromosome than of those on autosomes all point to a much higher mutation rate in human males than in females, as first pointed out by Haldane [Ann Eugen 13:262-271, 1947] in his classical study of X-linked hemophilia. The age of the father is the main factor determining the human spontaneous mutation rate, and probably the total mutation rate. The total mutation rate in Drosophila males of genes causing minor reduction in viability is at least 0.4 per sperm, and may be considerably higher. The great mutation load implied by a rate of approximately 1 per zygote can be greatly ameliorated by quasi-truncation selection. Corresponding data are not available for the human population. The evolution rate of pseudogenes in primates suggests some 10(2) new mutations per zygote. Presumably the overwhelming majority of these are neutral, but even the approximate fraction is not known. Statistical evidence in Drosophila shows that mutations with minor effects cause about the same heterozygous impairment of fitness as those that are lethal when homozygous. The magnitude of heterozygous effect is such that almost all mutant genes are eliminated as heterozygotes before ever becoming homozygous. Although quantitative data in the human species are lacking, anecdotal information supports the conclusion that partial dominance is the rule here as well. This suggests that if the human mutation rate were increased or decreased, the effects would be spread over a period of 50-100 generations.
Environ Mol Mutagen 1993
PMID:How much do we know about spontaneous human mutation rates? 844 42

The human MIC2 gene is pseudoautosomal and in females it escapes X inactivation. At the 5' end of the gene a 1.2-kb-long CpG island has been identified that is unmethylated on the active X, the inactive X, and on the Y chromosome. We have demonstrated by 5' RACE experiments that this region contains the transcription start site of the gene. To better characterize this CpG island, we have investigated the interaction between this region and nuclear proteins in vitro by using DNA gel mobility shift and DNase I footprinting techniques. Band shift experiments with HeLa cell nuclear extract have indicated that all the island is involved in multiple interactions with nuclear proteins. Experiments with a eukaryotic purified Sp1 protein have shown that this factor specifically binds to several sites of the island. Three DNase I protected footprints have been identified in the region between nucleotides -122 and +34 with respect to the transcription initiation site. By using a recombinant Sp1 protein, we have shown that all the footprints are due to the binding of Sp1. The sequences of two footprints correspond to the decanucleotide binding site for Sp1, the sequence of the third one does not contain any published Sp1 recognition site.
Somat Cell Mol Genet 1993 Jan
PMID:Multiple DNA-protein interactions at the CpG island of the human pseudoautosomal gene MIC2. 846 Mar 98

Double fluorescence in situ hybridization (FISH) was used to detect sex chromosomes in decondensed human sperm nuclei. Biotinylated X chromosome specific (TRX) and digoxigenin-labeled Y chromosome specific (HRY) probes were simultaneously hybridized to sperm preparations from 12 normal healthy donors. After the hybridization, the probes were detected immunocytochemically, using two different and independent affinity systems. Ninety-six percent of the 12,636 sperm showed fluorescent labeling, of which 47.4% were haploid X and 46.8% were haploid Y. A frequency of 0.46% of XX-bearing sperm (0.28% disomic, 0.18% diploid) and 0.38% YY-bearing sperm (0.21% disomic, 0.17% diploid) was found. The overall proportions of X- and Y-bearing sperm in the ejaculates were 47.9% and 47.2%, respectively, which was not significantly different from the expected 50:50 ratio. In addition 0.21% of cells appeared to be haploid XY-bearing sperm, 0.62% were diploid XY-bearing cells, and 0.05% of cells were considered to be tetraploid cells. The application of double FISH to human sperm using X-chromosome and Y-chromosome probes has allowed a more accurate assessment of the sex chromosal complements in sperm than single FISH method and quinacrine staining for Y-bodies.
Mol Reprod Dev 1993 Mar
PMID:Simultaneous detection of X- and Y-bearing human sperm by double fluorescence in situ hybridization. 847 Dec 53

Aqueous two-phase partition involving thin-layer counter current distribution (TLCCD) has been used to assess surface heterogeneity of ejaculated bovine sperm. When partitioned in charge-insensitive aqueous two-phase systems, which detect non-charge associated surface properties, the sperm fractionates into two distinct populations. Using a Y-chromosome-specific DNA marker, it has been shown that one of these populations is enriched in Y chromosome bearing sperm. However, this population is not pure--it consists of 80% Y sperm, with the other 20% being X sperm. All the sperm in the original population that had begun to undergo the acrosome reaction were separated into this same peak; the sex chromosome composition of these sperm is unknown. Since the aqueous partition of sperm is based on surface properties these results suggest that two populations of Y sperm exist that have different surface characteristics.
Mol Reprod Dev 1993 Mar
PMID:Separation of bovine X and Y sperm based on surface differences. 847 Dec 55

Eighteen yeast artificial chromosome (YAC) clones containing alphoid satellite DNA and adjacent sequences from the human Y chromosome have been identified from three different YAC libraries. Restriction site mapping of the genomic alphoid arrays and the YACs has allowed seven of the alphoid clones to be positioned on the arrays. Three clones extend into flanking sequences. At one edge the alphoid DNA is highly diverged and is flanked by a small block of the 48 base-pair satellite, dispersed moderately repeated sequences and a separate short alphoid array. More distal sequences are Y-specific. At the other edge there is much less divergence and the alphoid DNA is flanked by an Alu sequence and the five base-pair satellite.
J Mol Biol 1993 Apr 05
PMID:Structure of the sequences adjacent to the centromeric alphoid satellite DNA array on the human Y chromosome. 847 34

When the mouse Y chromosome of Mus musculus domesticus is placed onto the C57BL/6J genetic background, half of the XY progeny develop bilateral ovaries and the female phenotype, but lack regular estrous cyclicity and lose embryos after fertilization. In the present study, we compared the endocrinological activity of XY ovaries with XX ovaries during postnatal development by measuring steroids in the incubation medium by radioimmunoassay. At 1 day postpartum (d.p.p.), production of progesterone and estradiol was significant while testosterone was undetectable in both ovaries. At 14 and 35 d.p.p., amounts of testosterone and estradiol produced by XY ovaries were half of those by XX ovaries. Production of progesterone by XY ovaries was slightly higher than XX ovaries at 14 d.p.p., but only half of that at 35 d.p.p. Addition of gonadotropins increased testosterone production by XX ovaries but not by XY ovaries at either 14 or 35 d.p.p. Progesterone production in XY ovaries at 35 d.p.p. was increased by gonadotropins to a much lesser extent than in XX ovaries. Gonadotropins increased estradiol production similarly in both ovaries at 35 d.p.p. Striking differences were found in the histochemical distribution of 3 beta-hydroxysteroid dehydrogenase between XY and XX ovaries at 14, but not at 35 d.p.p. In conclusion, the XY ovary develops abnormal endocrine features during the postnatal period, which likely lead to the fertility problems at puberty.
J Steroid Biochem Mol Biol 1993 Apr
PMID:Endocrine differentiation of the XY sex-reversed mouse ovary during postnatal development. 849 34

Melandrium album, a dioecious plant species, has two heteromorphic sex chromosomes with the XY constitution typical for male and the XX for female plants. This plant represents an experimental model system of sex determination in which the Y chromosome plays a strongly dominant male role. We present data on the overall transcriptional activities of M. album sex chromosomes. DNA methylation patterns were analysed directly at the level of chromosomes using in situ nick-translation of fixed root mitotic chromosomes after nuclease digestion and in vivo labelling with S-adenosyl-L-[methyl-3H] methionine as donor of methyl groups. Both techniques revealed that the two X chromosomes of female plants had different levels of DNA methylation. Cell treatment with a DNA hypomethylating drug, 5-azacytidine, significantly influenced the labelling densities. These results imply that in female M. album plants, one of the two X chromosomes may be hypermethylated and inactive as described for mammalian cells (Lyon hypothesis). A similar analysis made on male cells displayed a similar relative levels of methylation in autosomes and sex chromosomes, thus indicating the transcriptional activity of both Y and X male chromosomes.
Mol Gen Genet 1993 May
PMID:DNA methylation of sex chromosomes in a dioecious plant, Melandrium album. 851 Jun 48

The classical conception of the chromosomal mechanism of sex determination presumes a chromosome unique for and determining the heterogametic sex. On the basis of recent evidence, however, this picture is becoming increasingly complex, with a multitude of genes appearing to interact simultaneously or successively to bring about the gonadal phenotype. The genes identified so far that are thought to be involved in the process of human sex determination are distributed on various chromosomes, but the consecution of their function remains to be elucidated. To the Y chromosome only a relative role can be ascribed, and it has not yet been established which gene is on top of the cascade. All of the genes under discussion are involved in transcriptional control, and at least the majority of them appear to exert pleiotropic effects. The regulation of their expression must still be defined, and it will be a long way before a link to gonadal morphogenesis is ultimately found.
J Mol Med (Berl) 1995 Jul
PMID:The molecular genetics of human sex determination. 852 Sep 65


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