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J Weissenbach

Publications and source records attributed to J Weissenbach.

At least 307 records · Page 17Linked to original sources
PubMed1990

[The Y chromosome and sex determination].

The structure and function of the human Y chromosome have been approached by molecular genetics. The use of Y-derived DNA probes to analyze the Y chromosome of patients with sexual differentiation abnormalities allowed the construction of a deletion map localizing TDF (testis determining factor) in the terminal part of the short arm. These studies culminated recently in the isolation of a candidate gene for the TDF locus. Nevertheless, the existence of a related locus on the X chromosome does not fit with the simple hypothesis of a single Y-located gene for testis differentiation. The finding of a strictly homologous region at the tip of the short arms of X and Y chromosomes allowed the characterization of another major property of the sex chromosomes. These so called pseudoautosomal DNA sequences show only a partial sex linkage and can be exchanged between X and Y chromosomes during male meiosis. Genetic analysis and determination of the physical length of the pseudoautosomal region show that it is subjected in male meiosis, to a recombination rate about 20 times higher than the mean value of the human genome. In 1966, Ferguson-Smith proposed that an abnormal cross-over was responsible for both types of sex inversions in humans: XX males and XY females. Segregation analysis of the pseudoautosomal loci in these patients has demonstrated the validity of this hypothesis and shown the existence of sex inversions unrelated to the TDF locus. The construction of a detailed map of the human Y chromosome enables the search for new genes (H-Y antigen, fertility gene(s]. The finding of several homologous regions on the sex chromosomes confirms the hypothesis of a common origin and should help to understand the establishment of sex determination and X inactivation mechanisms during mammalian evolution.

Chromosome Deletion↗
PubMed1989

Exchange of terminal portions of X- and Y-chromosomal short arms in human XY females.

Human Y(+) XX maleness has been shown to result from an abnormal terminal Xp-Yp interchange that can occur during paternal meiosis. To test whether human XY females are produced by the same mechanism, we followed the inheritance of paternal pseudoautosomal loci and Xp22.3-specific loci in two XY female patients. Y-specific sequences and the whole pseudoautosomal region of the Y chromosome of their fathers were absent in these patients. However, the entire pseudoautosomal region and the X-specific part of Xp22.3 distal to the STS locus had been inherited from the X chromosome of the respective father. This Xp transfer to Yp was established by in situ hybridization experiments showing an Xp22.3-specific locus on Yp in both cases. Such results demonstrate that an abnormal and terminal X-Y interchange generated the rearranged Y chromosome of these two XY females; they appear to be the true countertype of Y(+) XX males. In these patients, who also display some Turner stigmata, the Y gene(s) involved in this phenotype is (are) localized to interval 1 or 2. If the loss of such gene(s) affects fetal viability, their proximity to TDF would account for the underrepresentation of interchange 46,XY females compared with Y(+) XX males.

Blotting, Southern↗
PubMed1988

Mapping the human Y chromosome.

This paper reviews past and present trends in mapping the human Y chromosome. So far, mapping has essentially used a combination of cytogenetic and molecular analyses of Y-chromosomal anomalies and sex reversal syndromes. This deletion mapping culminated recently in the isolation of the putative sex-determining locus TDF. With the availability of new separation and cloning techniques suited for large size fragments (over 100 kilobases), the next step will consist rather in the establishment of a physical map of fragments of known physical sizes. This may allow the definition of several variants of the human Y chromosome differing by the order or location of DNA sequences along the molecule.

Chromosome Deletion↗
PubMed1988

Physical mapping of the human pseudo-autosomal region; comparison with genetic linkage map.

A long-range restriction map of the pseudo-autosomal or exchange pairing region (corresponding to the terminal parts of the short arms of the human sex chromosomes) has been established using pulsed field gel electrophoresis. A total of seven loci have been located on this physical map based essentially on the analysis of 45,X Turner genomes. The region spans a total of 2600 kb. The 5' end of the MIC2 gene maps at less than 80 kb from the proximal pseudo-autosomal boundary. Since the total pseudo-autosomal linkage interval represents approximately 50% of recombination at male meiosis, 1 cM corresponds to 50-60 kb. This is consistent with the almost 20-fold increase in recombination frequency observed in male versus female meiosis in this region. The present data show no distortion between both physical and linkage maps. The distribution of the CpG-rich restriction sites is notably disequilibrated. A large subset of these sites is concentrated within the 500 kb closest to the telomere whereas others appear in clusters (probably HTF islands) scattered in the rest of the pseudo-autosomal region.

Blotting, Southern↗
PubMed1988

X-Y crossing over in the chimpanzee.

Single-copy DNA sequences defining several pseudoautosomal loci on the human sex chromosomes are shown to be highly conserved in the genome of the chimpanzee. Segregation analysis of polymorphic pseudoautosomal probes in a chimpanzee pedigree revealed that the transmission of the paternal alleles was not strictly sex-linked. In situ hybridization localized the pseudoautosomal probe 29C1 specifically to Xp22-Xpter and to Yq12.2-Yqter on the chimpanzee sex chromosomes. Thus, our results demonstrate the existence of homologous segments on the chimpanzee X and Y chromosomes, which regularly undergo recombinatory exchange in male meiosis. The chimpanzee is now the third mammalian species, besides man and mouse, in which there is genetic evidence for a pseudoautosomal segment on the sex chromosomes.

Animals↗
PubMed1987

A sex chromosome rearrangement in a human XX male caused by Alu-Alu recombination.

Human XX maleness is often due to the presence of Y-specific DNA, resulting from abnormal interchange of terminal parts of the short arms of the X and Y chromosomes. In an XX male, a rearrangement is observed at locus DXYS5, the most proximal Yp locus detected in this patient. Cloning and analysis of the rearranged DNA fragment revealed pseudoautosomal sequences located beyond the breakpoint. We propose that this XX male arose by abnormal crossing over between DXYS5 on the Y chromosome and a pseudoautosomal locus on the X chromosome during paternal meiosis. Sequence analysis of the junction shows that homologous recombination occurred between two Alu sequences from these otherwise nonhomologous regions. The site of recombination is localized to the putative transcription promoter region of the Alu sequences.

Cells, Cultured↗
PubMed1987

An abnormal terminal X-Y interchange accounts for most but not all cases of human XX maleness.

To determine if human XX maleness results from an abnormal chromosomal X-Y interchange, we studied the inheritance of the paternal pseudoautosomal region in nine patients. Those six patients in whom Y-specific DNA was found (Y(+)) inherited the entire pseudoautosomal region from the paternal Y chromosome and lost that of the paternal X chromosome. Moreover, in three Y(+) cases, we observed the deletion of a paternal Xp locus tightly linked to the pseudoautosomal region. These results definitively show that an abnormal and terminal X-Y interchange during paternal meiosis causes Y(+)XX maleness. In contrast, no abnormal X-Y interchange was observed in any of the three Y(-) cases analyzed, suggesting that maleness can occur in the absence of any Y-specific DNA.

Alleles↗
PubMed1987

Two highly polymorphic minisatellites from the pseudoautosomal region of the human sex chromosomes.

Two pseudoautosomal loci DXYS15 and DXYS17 from the pairing region of the human sex chromosomes display a high variability with at least eight alleles each. The structural elements responsible for the polymorphisms have been isolated and sequenced. In both cases the variations result from DNA rearrangements occurring in tandemly repeated sequences (minisatellites) of 21-29 nucleotides for DXYS15 and 28-33 nucleotides for DXYS17. At reduced stringency, the DXYS15 minisatellite detects other hypervariable sequences located in other parts of the genome and hence represents a new family of minisatellites. In contrast to most other known hypervariable families, the DXYS15 hypervariable sequence displays a very high AT content.

Alleles↗
PubMed1987

Absence of Y-specific DNA sequences in human 46,XX true hermaphrodites and in 45,X mixed gonadal dysgenesis.

A search for Y-specific DNA sequences has been performed in a sample of seven 46,XX true hermaphrodites and one 45,X mixed gonadal dysgenesis case and compared with a sample of 11 XX males. Using six Y-specific DNA probes no hybridization signal was obtained in the hermaphrodite group; in contrast, all XX males gave a positive signal with at least one probe. This difference is statistically highly significant. We conclude that the aetiology of true hermaphroditism is different from that of the XX male syndrome. As all cases of the hermaphrodite group are positive for the serological sex-specific antigen (Sxs) it is concluded that this antigen can be present even in the absence of Y-specific DNA.

DNA↗
PubMed1987

Conservation of human-derived pseudoautosomal sequences on the sex chromosomes of the great apes.

In situ hybridization using a repeated element specific for the human pseudoautosomal region, DXYZ2, revealed the presence of this repeat in the early replicating portion of the sex chromosomes of the great apes. This segment, as well as the DXYZ2 repeats, are located in band Xp22.3 and in a telomeric or subtelomeric region of the Y chromosome. These segments may therefore represent pseudoautosomal regions, as in man.

Animals↗
PubMed1987

Normal and abnormal interchanges between the human X and Y chromosomes.

A single obligatory recombination event takes place at male meiosis in the tips of the X- and Y-chromosome short arms (i.e. the pseudoautosomal region). The crossover point is at variable locations and thus allows recombination mapping of the pseudoautosomal loci along a gradient of sex linkage. Recombination at male meiosis in the terminal regions of the short arms of the X and Y chromosomes is 10- to 20-fold higher than between the same regions of the X chromosomes during female meiosis. The human pseudoautosomal region is rich in highly polymorphic loci associated with minisatellites. However, these minisatellites are unrelated to those resembling the bacterial Chi sequence and which possibly represent recombination hotspots. The high recombination activity of the pseudoautosomal region at male meiosis sometimes results in unequal crossover which can generate various sex-reversal syndromes.

Base Sequence↗
PubMed1986

Complete cDNA-derived amino acid sequence of rat brown fat uncoupling protein.

Cloned cDNAs corresponding to the mitochondrial uncoupling protein of rat brown adipose tissue have been sequenced and the complete amino acid sequence of this unique membranous component is given. The N-terminal sequence of this protein is almost identical to the 14-residue N-terminal sequence previously determined by others for the hamster uncoupling protein. The uncoupling protein has no N-terminal signal extension. We found a significant sequence homology between the uncoupling protein and the ADP/ATP carrier and propose that the nucleotide binding site of the uncoupling protein is localized at the C-terminal end.

Adipose Tissue, Brown↗
PubMed1986

A 45,X male with a Yp/18 translocation.

A patient described as a 45,X male (Forabosco et al. 1977) was examined for the presence of Y-specific DNA by using various probes detecting restriction fragments from different regions of the Y chromosome. Positive hybridization signals were obtained for Yp fragments only. In situ hybridization with two different probes, pDP31 and the pseudoautosomal probe 113F, led to a clear assignment of the Yp sequences to the short arm of one chromosome 18. Cytogenetically, the presence of all of Yp including the Y centromere on 18p could be demonstrated replacing a segment of similar size of 18p. Thus, the Y/18 translocation chromosome is dicentric structurally, but it was shown to be monocentric functionally with the no. 18 centromere active. Gene dosage studies with the probe B74 defining a sequence at 18p11.3 demonstrated a single dose of this sequence in the patient. In agreement with these observations, the patient shows clinical signs of the 18p-syndrome. It is concluded that in XO males in general, the X is of maternal origin while the maleness is due to a de novo Y/autosome translocation derived from the father. Depending on the nature of the autosomal deficiency caused by the Y/autosome translocation, the patient may have congenital malformations.

Child↗
PubMed1986

Regulation of human gamma-interferon and beta-interferon gene expression in PHA-activated lymphocytes.

Two interferon (IFN) messengers were synthesized in phytohemagglutinin (PHA)-activated lymphocytes: IFN-gamma mRNA and a messenger hybridizing with the IFN-beta 2 probe. They were induced rapidly and declined at a stage when overall RNA was still efficiently transcribed. The IFN-beta 2 mRNA (15S) present in the lymphocytes was slightly different from its fibroblastic counterpart (14S). The kinetics of the accumulation and decay of both lymphocyte IFN messengers differed when assessed by hybridization with the two IFN probes, IFN-gamma mRNA was not detected before mitogenic activation and accumulated for up to 15 h postactivation, while IFN-beta 2 mRNA accumulated even in the absence of PHA activation for up to 5 h, even though the activation raised the IFN-beta 2 mRNA level at 5 h. The disappearance of IFN messengers was prevented when cycloheximide was added 5 h after PHA activation, when the transcription of both messengers had already been turned on, suggesting the presence of the repressor mechanism proposed for IFN-beta 1 and IFN-beta 2 mRNAs in fibroblasts. In the absence of PHA activation, cycloheximide did not induce IFN-beta 2 mRNA transcription as it did in fibroblasts and moreover prevented the accumulation of the messenger observed in the control cells. In contrast to IFN-beta 2 mRNA, cycloheximide treatment of lymphocytes produced a slight accumulation of IFN-gamma mRNA. This accumulation was already detectable 6 h posttreatment and its level remained unchanged for up to 24 h. Addition of actinomycin D, 5 h after PHA activation, did not impair the shut off and accelerated the decay of IFN messengers.

Cells, Cultured↗