Showing papers on "X chromosome published in 1984"
TL;DR: Linkage analysis with four X chromosome loci indicates that mdx maps in the Hq Bpa region of the mouse X chromosome, which gives a gene order of mdx-Tfm-Pgk-1-Ags, the same as for the equivalent genes on the human X chromosome.
Abstract: An X chromosome-linked mouse mutant (gene symbol, mdx) has been found that has elevated plasma levels of muscle creatine kinase and pyruvate kinase and exhibits histological lesions characteristic of muscular dystrophy. The mutants show mild clinical symptoms and are viable and fertile. Linkage analysis with four X chromosome loci indicates that mdx maps in the Hq Bpa region of the mouse X chromosome. This gives a gene order of mdx-Tfm-Pgk-1-Ags, the same as for the equivalent genes on the human X chromosome.
1,677 citations
01 Sep 1984
TL;DR: The results suggest that the number of genes required zygotically for normal embryonic patterning is small and that most, if not all such loci, are represented by point mutations in the collection.
Abstract: In order to identify X-chromosomal genes required inDrosophila for early patterning and morphogenesis, we examined embryos hemizygous for EMS-induced lethal mutations to determine which of those mutations cause gross morphological defects. Embryos from 2711 lethal lines, corresponding to 3255 lethal point mutations were studied. Only 21% caused death during embryogenesis and of these, only one-sixth, or 3% of the total lethals, were associated with defects visible in the final cuticle pattern. Of the 114 point mutants causing visible cuticle defects, 76 could be assigned to 14 complementation groups. An additional 25 mutations mapping to regions of the X-chromosome not covered by male fertile duplications were assigned to six complementation groups based on similarities of map position and phenotype. Thirteen mutations could not be assigned to complementation groups. All mutations allowed normal development through the cellular blastoderm stage, the first defects associated with the earliest acting loci being observed shortly after the onset of gastrulation. The phenotypes of the various loci range from alterations in segment pattern or early morphogenetic movements to defects in final pigmentation and denticle morphology.Cuticle preparations were also examined for 63 deletions spanning in total 74% of the X-chromosome, as well as for 8 deletions and point mutations derived in saturation mutagenesis screens of the fourth chromosome (Hochman 1976). With the exception of defects in head morphology and defects in cuticle differentiation, none of the hemizygous deletions showed phenotypes other than those predicted by point mutations known to lie in those regions. No deletion caused new or unknown alterations in gastrulation, segmentation or cuticle pattern.These results suggest that the number of genes required zygotically for normal embryonic patterning is small and that most, if not all such loci, are represented by point mutations in our collection.
479 citations
TL;DR: The results of studies on structural and functional memthrane abnormalities in cells other than muscle tissue, e.g., erythrocytes, lymphocytes and cultured fibroblasts, indicate that the DMD mutation is probably demonstrable in these tissues, but most of the findings are still difficult to reproduce or even controversial.
Abstract: Duchenne muscular dystrophy (DMD) is the most common sex linked lethal disease in man (one case in about 4000 male live births). The patients are wheelchair bound around the age of 8-10 years and usually die before the age of 20 years. The mutation rate, estimated by different methods and from different population studies, is in the order of 7 X 10(-5), which is higher than for any other X-linked genetic disease. Moreover, unlike other X linked diseases such as hemophilia A or Lesh-Nyhan's disease, there seems to be no sex difference for the mutation rates in DMD. Several observations of DMD in girls bearing X-autosomal translocations and linkage studies on two X chromosomal DNA restriction fragment length polymorphisms indicate that the DMD locus is situated on the short arm of the X chromosome, between Xp11 and Xp22. It may be of considerable length, and perhaps consisting of actively coding and non-active intervening DNA sequences. Thus unequal crossing over during meiosis in females could theoretically account for a considerable proportion of new mutations. However, there is no structurally or functionally abnormal protein known that might represent the primary gene product, nor has any pathogenetic mechanism leading to the observed biochemical and histological alterations been elucidated. Among the numerous pathogenetic concepts the hypothesis of a structural or/and functional defect of the muscular plasma membrane is still the most attractive. It would explain both the excess of muscular constituents found in serum of patients and carriers, such as creatine kinase (CK), as well as the excessive calcium uptake by dystrophic muscle fibres, which, prior to necrosis, could lead to hypercontraction, rupture of myofilaments in adjacent sarcomeres and by excessive Ca uptake to mitochondrial damage causing crucial energy loss. The results of studies on structural and functional membrane abnormalities in cells other than muscle tissue, e.g., erythrocytes, lymphocytes and cultured fibroblasts, indicate that the DMD mutation is probably demonstrable in these tissues. However, most of the findings are still difficult to reproduce or even controversial. DMD is an incurable disease; therefore most effort, in research as well as in practical medicine, is concentrated upon its prevention.(ABSTRACT TRUNCATED AT 400 WORDS)
390 citations
TL;DR: The D. melanogaster DNA segment in the recombinant phage lambda Dm2L1 contains at least eight copies of a tandemly repeated 1250-base pair sequence (henceforth called the 2L1 sequence), which is present on both the X and Y chromosomes.
Abstract: The D. melanogaster DNA segment in the recombinant phage λDm2L1 contains at least eight copies of a tandemly repeated 1250-base pair (bp) sequence (henceforth called the 2L1 sequence). Testes from XO D. melanogaster males contain an abundant 800-base RNA species that is homologous to a 520-bp region of the 2L1 sequence. Blotting experiments show that the 2L1 sequence is repeated in the D. melanogaster genome and is present on both the X and Y chromosomes. With the use of X-Y translocations, the 2L1 sequence has been mapped to a region between kl-1 and kl-2 on the long arm of the Y chromosome. In Oregon-R wild type there are an estimated 200 copies of the 2L1 sequence on the X chromosome and probably at least 80 copies on the Y chromosome. In some other strains the repetition frequency on the Y chromosome is about the same, but the copy number on the X chromosome is much reduced. On the basis of the five strains investigated, there is a correlation between copy number of the 2L1 sequence on the X chromosome and the presence of a particular allele of the Stellate locus (Ste; 1-45.7). It seems that low copy number corresponds to Ste + and high copy number corresponds to Ste. The Ste locus determines whether single or star-shaped crystals are observed in the spermatocytes of XO males. Studies using D. simulans and D. mauritiana DNA show that the 2L1 sequence is homologous to restriction fragments in male DNA but not female DNA, indicating that this sequence is present only on the Y chromosome in these two species. In DNA derived from D. erecta, D. teissieri and D. yakuba, there is very little, if any, hybridization with the 2L1 sequence probe.
377 citations
Journal Article•
TL;DR: Fifteen human X-chromosome-specific DNA fragments, localized to particular regions of that chromosome, were used to search for restriction fragment length polymorphisms, which allowed identifying females, from pedigrees segregating three X-linked diseases, who were multiply heterozygous for polymorphic loci spread throughout the X chromosome.
Abstract: Fifteen human X-chromosome-specific DNA fragments, localized to particular regions of that chromosome, were used to search for restriction fragment length polymorphisms. A screening panel prepared by digesting DNA from only two females and one male with 24 restriction enzymes was sufficient to reveal two-allele polymorphisms among one-third of the probes tested. These polymorphisms, as theoretically anticipated, showed minor allele frequencies above 20%, as a rule. Such high-frequency polymorphism allowed identifying females, from pedigrees segregating three X-linked diseases, who were multiply heterozygous for polymorphic loci spread throughout the X chromosome. In addition, two of the 24 enzymes tested with these X-specific probes, Msp I and Taq I, generate fragment sizes in DNA-blotting experiments that, on average, are significantly larger than expected from nearest neighbor predicted recognition site frequencies.
300 citations
TL;DR: X chromosome-specific recombinant DNA probes which can detect restriction fragment length polymorphisms have been used to localize the XLRP gene(s) to a subregion of the X chromosome using linkage analysis, and one of the probes, L1.28, has been shown to be closely linked to XLRP in five kindreds, indicating that this probe is potentially useful for carrier detection and early diagnosis in about 40% of cases.
Abstract: Retinitis pigmentosa (RP) is a group of retinal degenerations characterized by progressive visual field loss, night blindness and pigmentary retinopathy1. Its prevalence is in the region of 1–2 in 5,000 of the general population, making it one of the commoner causes of blindness in early and middle life2,3. Although 36–48% of RP patients are isolated cases, the remainder show autosomal dominant, autosomal recessive or X-linked modes of inheritance4,5. The X-linked variety (XLRP) is found in 14–22% of RP families in the UK2,5. In the present study, X chromosome-specific recombinant DNA probes which can detect restriction fragment length polymorphisms have been used to localize the XLRP gene(s) to a subregion of the X chromosome using linkage analysis. One of the probes, L1.28, has been shown to be closely linked to XLRP in five kindreds,, with 95% confidence limits of 0–15 centimorgans (maximum LOD score of 7.89 at a distance of 3 centimorgans). This suggests that the XLRP locus lies on the proximal part of the short arm of the X chromosome. This probe is potentially useful for carrier detection and early diagnosis in about 40% of cases, provided that genetic heterogeneity can be excluded by analysis of further families.
276 citations
TL;DR: Observations indicate that methylation of housekeeping genes on the X chromosome is the same as that of autosomal ones and that the overall pattern andmethylation of multiple sites within a cluster may cooperate to facilitate transcription.
Abstract: To explore the role of DNA methylation in maintaining dosage compensation of X chromosome-linked genes and in regulating the transcriptional activity of "housekeeping" genes, we characterized DNA methylation of active, inactive, and derepressed alleles at the locus for hypoxanthine phosphoribosyltransferase (HPRT) on the human X chromosome. The methylation of Hpa II and Hha I sites in HPRT alleles on the active X chromosome was the same in all tissues. The consensus pattern includes hypomethylation of 5' clustered sites and extensive methylation of the 3' sequence. The striking feature of methylation of inactive X-chromosome alleles is nonuniformity and less extensive hypomethylation of the 5' cluster. Analysis of HPRT alleles reactivated in response to 5-azacytidine showed at least partial restoration of the consensus pattern. These observations indicate that methylation of housekeeping genes on the X chromosome is the same as that of autosomal ones and that the overall pattern and methylation of multiple sites within a cluster may cooperate to facilitate transcription. Furthermore, the fidelity of methylation of the active allele and the extensive drift in methylation of the inactive allele suggest that mechanisms involved in X-chromosome dosage compensation may be directed at the active rather than inactive X chromosome.
268 citations
TL;DR: DXYS1, a site showing greater than 99% DNA sequence homology between the human X and Y chromosomes, maps to the X long arm and to the Y short arm, suggesting an X–Y transposition during human evolution.
Abstract: DXYS1, a site showing greater than 99% DNA sequence homology between the human X and Y chromosomes, maps to the X long arm and to the Y short arm. In great apes, sequences homologous to DXYS1 are found only on the X chromosome. These findings suggest an X–Y transposition during human evolution.
223 citations
21 Jul 1984
198 citations
TL;DR: The data suggest that the overall pattern of methylation, rather than methylation of specific sites, plays a role in the maintenance of X chromosome inactivation.
Abstract: Previous theoretical considerations and some experimental data have suggested a role for DNA methylation in the maintenance of mammalian X chromosome inactivation. The isolation of specific X-encoded sequences makes it possible to investigate this hypothesis directly. We have used cloned fragments of the human hypoxanthine phosphoribosyltransferase (HPRT) gene and methylation-sensitive restriction enzymes to study methylation patterns in genomic DNA of individuals with different numbers of X chromosomes and in somatic cell hybrid lines containing human X chromosomes that are either active or inactive or have been reactivated by treatment with 5-azacytidine. The results of these analyses show that there is hypomethylation of active X chromosomes relative to inactive X chromosomes in the 5' region of this gene. In the middle region of the gene, however, a site that is consistently undermethylated on inactive X chromosomes was identified. Taken together, the data suggest that the overall pattern of methylation, rather than methylation of specific sites, plays a role in the maintenance of X chromosome inactivation.
195 citations
TL;DR: It has been shown that fem-1(+) is part of the sex-determination pathway and has two distinct functions: in the soma it prevents the action of tra-1, thereby allowing male development to occur, and in the germline it is necessary for spermatogenesis in both sexes.
TL;DR: Using several of these Y-specific single copy probes, this study definitively demonstrate the presence of Y-chromosomal material in the genome of some 46,XX human males, implying a genetic heterogeneity of these patients.
Abstract: In humans, XX maleness is the best known example of a sex reversal syndrome occurring with an incidence of one XX male among approximately 20,000 to 30,000 newborn boys. The karyotypes of the majority of these individuals are apparently normal, with respect to the numbers and structure of the chromosomes, but is in contradiction with the phenotypic sex which they display. XX maleness may be either a non Y-related mechanism triggered by a mutation on another chromosome or could be the result of the expression of some cytogenetically undetectable Y chromosome material present in the genome of such individuals. Recently, a number of human Y-specific single copy probes have been isolated. In this study, using several of these Y-specific probes we definitively demonstrate the presence of Y-chromosomal material in the genome of some 46,XX human males. These XX males carry only a fraction of the human Y chromosome. In the three positive cases reported here, presence of inclusive overlapping chromosomal fragments has been detected, implying a genetic heterogeneity of these patients.
TL;DR: The hybridization pattern suggests that this multiplicity has been generated by two different mechanisms: first the generation of approximately 40 different sequences, which were subsequently amplified (probably by tandem duplication), and secondly the generation and amplification of an intron‐less GAPD pseudogene, which is located in the p22‐p11 region of the human X chromosome.
Abstract: In an experiment designed to find sequences common to a skeletal muscle cDNA library and an X chromosome specific library, we have isolated cDNA clones corresponding to glyceraldehyde 3 phosphate dehydrogenase (GAPD), (whose gene is assigned to chromosome 12), and a DNA fragment from the X chromosome short arm which contains an intron-less GAPD pseudogene. A 1210-bp cDNA sequence has been established which covers all of the protein-coding region, most of the 5' non-coding region and part of the 3' non-coding region. It corresponds to the major (and possibly unique) GAPD mRNA present in skeletal muscle. Unexpectedly, the amino acid sequence derived from the cDNA clones differs at 10% of the residues from that established for the human protein purified from skeletal muscle. The X-linked pseudogene has been localised in the p22-p11 region of the human X chromosome. It has the structure of a complete retrotranscript of a processed mRNA, including the poly(A) tail and is 96% homologous to the cDNA sequence. The pseudogene is flanked by a 15-bp direct repeat, and an Alu-like sequence is found in the 3'-flanking region. About 25 GAPD sequences are found in the human genome, 12 of which have high homology to the cDNA probe. A similar complexity is found in hamster. In contrast, the mouse genome contains an amazing number of GAPD related fragments (at least 200). The hybridization pattern suggests that this multiplicity has been generated by two different mechanisms: first the generation of approximately 40 different sequences, which were subsequently amplified (probably by tandem duplication).
TL;DR: It is demonstrated that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance and have implications for the genetic organization of this portion of the human X chromosome.
Abstract: We studied two families with an inherited deletion of the short arm of an X chromosome (Xp) in which affected male offspring have epiphyseal stippling in infancy (chondrodysplasia punctata), nasal hypoplasia, ichthyosis, and mental retardation. The presence of ichthyosis and the apparent pattern of X-linked recessive inheritance prompted investigation of the short arm of the X chromosome through studies of genetic markers and focused cytogenetic analysis. Biochemical studies suggested that there was a deletion of three genes previously mapped to the X-chromosome short arm, including the steroid sulfatase locus, the Xg locus, and the M1C2X locus. Prometaphase chromosomes demonstrated a deletion of Xp at p22.32 in the affected boys, in their obligate-carrier mothers, and in 11 of 25 women at risk as potential carriers. The women carrying the Xp deletion had normal gonadal function and fertility but were shorter than the noncarriers in their families (P less than 0.00001). These findings have implications for the genetic organization of this portion of the human X chromosome and demonstrate that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance.
TL;DR: Evidence is presented that pairing between the human X and Y chromosomes could be more extensive at early pachytene than has previously been supposed and could involve even the entire euchromatic portion of the Y chromosome.
Abstract: Evidence is presented that pairing between the human X and Y chromosomes could be more extensive at early pachytene than has previously been supposed and could involve even the entire euchromatic portion of the Y chromosome. Following desynapsis over the major part of the X and Y axes, a small paired segment of Xp and Yp remains into late pachytene. Association between the distal tips of Xq and Yq can also be observed in about one half of the spermatocytes examined. A hypothesis linking meiotic pairing to early replicating sites along the chromosomes is proposed.
TL;DR: Using a human X chromosome-specific DNA library, arbitrary single-copy DNA sequences that reveal useful restriction fragment length polymorphisms are found that reveal parental phase and determination of recombination frequencies by counting recombinant and nonrecombinant chromosomes.
Abstract: Using a human X chromosome-specific DNA library, we have found arbitrary single-copy DNA sequences that reveal useful restriction fragment length polymorphisms. The inheritance of these and other available polymorphic DNA markers has been studied in a series of unrelated three-generation families with large sibships. These families reveal parental phase and allow determination of recombination frequencies by counting recombinant and nonrecombinant chromosomes. The resulting genetic map indicates that the minimal distance from Xp22 to Xqter is 215 recombination units. The spacing of the marker loci is such that the majority of the loci on the X chromosome, including disease loci, will lie within 20 centimorgans of at least one of these loci.
TL;DR: Genetic analysis of male sterility in hybrids between these species shows that at least five loci are responsible for this reproductive isolation, which implies that the true genetic divergence for sterility is even greater than previously thought.
Abstract: Drosophila simulans and Drosophila mauritiana are closely related sibling species, the former cosmopolitan and the latter restricted to the small oceanic island of Mauritius. Genetic analysis of male sterility in hybrids between these species shows that at least five loci (one on each chromosome arm) are responsible for this reproductive isolation. This is the most loci that could have been detected with the techniques used and implies that the true genetic divergence for sterility is even greater. The effects of chromosome segments on the character are roughly additive, with the X-linked segment making the largest contribution to sterility. The large effect of X chromosomes on male-limited reproductive isolation and the frequent limitation of hybrid sterility to males may be attributable to fertility interactions between X and Y chromosomes. These results parallel what has been found in other Drosophila species and relate to recent theories of how reproductive isolation evolves in small founder populations.
TL;DR: A cDNA clone corresponding to factor IX has been used to detect homologous sequences in the human genome and should be useful for the detection of carriers of the hemophilia B trait and for prenatal diagnosis in informative families and, more generally, for the establishment of a linkage map of the human X chromosome.
Abstract: Hemophilia B is an X-linked disease caused by a functional deficiency in coagulation factor IX. A cDNA clone corresponding to factor IX has been used to detect homologous sequences in the human genome. All DNA fragments hybridizing to the probe, under medium- or high-stringency conditions, are X-linked, and the patterns obtained suggest that a single large (greater than or equal to 20 kilobases) gene is detected. The gene has been mapped to the q26-q27 region of the long arm of the X chromosome by hybridization to DNA from a panel of human-mouse hybrid cell lines. A search for restriction fragment length polymorphisms using seven restriction enzymes has led to the detection of a Taq I polymorphism, with allelic frequencies of about 0.71 and 0.29. This genetic marker should be useful for the detection of carriers of the hemophilia B trait and for prenatal diagnosis in informative families and, more generally, for the establishment of a linkage map of the human X chromosome.
TL;DR: Using both [3H] thymidine autoradiography and the BrdU-Hoechst 33258-Giemsa technique, lymphocytes and fibroblasts were found to show a preferential inactivation of the normal X suggesting the presence of a single mutant gene on the translocated X.
Abstract: A young female was diagnosed as having X-linked muscular dystrophy of the Duchenne type. Chromosome studies, including trypsin-Giemsa banding, Quinacrine fluorescence, and nucleolus organizer region (NOR) silver staining revealed an X-autosome reciprocal translocation t(X;21) (p21;p12). Utilizing both [3H] thymidine autoradiography and the BrdU-Hoechst 33258-Giemsa technique, lymphocytes and fibroblasts were found to show a preferential inactivation of the normal X suggesting the presence of a single mutant gene on the translocated X. This patient is one of seven reported cases of an X-linked muscular dystrophy associated with an X-autosome translocation. In all seven cases the exchange point in the X chromosome is in band p21 at or near the site of the Duchenne gene.
TL;DR: Structural and numerical abnormalities involved almost all chromosomes, except no. 19 and the X chromosome, which provides added support for the proposal that a 14q rearrangement involving band q11-12, with or without an accompanying break in 14q32, may confer a proliferative advantage on lymphocytes, especially on those of T cell origin.
TL;DR: A conserved transcribed component of the snake W chromosome satellite DNA (Bkm) from Drosophila and male mouse libraries is recovered, and it appears to be transcribed in a sex-specific and developmentally regulated manner.
Journal Article•
TL;DR: To facilitate the search for closely linked RFLPs, 16 cloned DNA sequences are regionally assigned to various portions of the human X chromosome, employing a large panel of somatic cell hybrids.
Abstract: Closely linked restriction fragment length polymorphisms (RFLPs) are potentially useful as diagnostic markers of genetic defects, and, in principle, RFLPs can be employed to construct a complete linkage map of the human genome. On the X chromosome, linkage studies are particularly rewarding because in man more than 120 X-linked genes are known. Thus, it is probable that each X-specific RFLP will be of use as a genetic marker of one or several X-linked disorders. To facilitate the search for closely linked RFLPs, we have regionally assigned 16 cloned DNA sequences to various portions of the human X chromosome, employing a large panel of somatic cell hybrids. These probes have been used to correlate genetic and physical distances on Xp, and it can be extrapolated from these data that the number and distribution of available Xq sequences will also suffice to span the long arm of the X chromosome.
TL;DR: The gene for the mitochondrial enzyme ornithine transcarbamylase was mapped to the short arm of the X chromosome by in situ hybridization experiments, with DNA complementary to the human ornithines transcarb amylase gene used as a probe.
Abstract: The gene for the mitochondrial enzyme ornithine transcarbamylase was mapped to the short arm of the X chromosome by in situ hybridization experiments, with DNA complementary to the human ornithine transcarbamylase gene used as a probe. A series of cell lines with X chromosome abnormalities was used to localize the gene to band Xp21.1. Because the gene maps near the Duchenne muscular dystrophy locus, the ornithine transcarbamylase probe may be useful in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy as well as of ornithine transcarbamylase deficiency.
TL;DR: Ribosomal RNA gene probes may be used to identify a junction fragment from the translocation site, allowing access to cloned segments of the X at or near the dmd gene and presenting a new approach to the study of this disease.
Abstract: Duchenne muscular dystrophy (DMD) is a severe X-linked disorder leading to early death of affected males. Females with the disease are rare, but seven are known to be affected because of a chromosomal rearrangement involving a site at or near the dmd gene on the X chromosome. One of the seven has a translocation between the X and chromosome 21. The translocation-derived chromosomes from this patient have been isolated, and the translocation is shown to have split the block of genes encoding ribosomal RNA on the short arm of chromosome 21. Thus ribosomal RNA gene probes may be used to identify a junction fragment from the translocation site, allowing access to cloned segments of the X at or near the dmd gene and presenting a new approach to the study of this disease.
TL;DR: A linkage study in 30 Becker muscular dystrophy kindreds using three cloned DNA sequences from the X chromosome which demonstrate restriction fragment length polymorphisms (RFLPs), suggests that the BMD gene is located on the short arm of the X chromosomes, in the p21 region.
Abstract: A linkage study in 30 Becker muscular dystrophy (BMD) kindreds using three cloned DNA sequences from the X chromosome which demonstrate restriction fragment length polymorphisms (RFLPs), suggests that the BMD gene is located on the short arm of the X chromosome, in the p21 region. The genes for Becker and Duchenne dystrophies must therefore be closely linked, if not allelic, and any future DNA probes found to be of practical use in one disorder should be equally applicable to the other. The linkage analysis also provides data on the frequency of recombination along the short arm of the X chromosome, and across the centromeric region.
Journal Article•
TL;DR: It is shown that MIC2X escapes X-inactivation on structurally normal and abnormal inactive human X chromosomes.
Abstract: Recently, it was shown that the cell surface antigen defined by the monoclonal antibody 12E7 is expressed by both the human X and Y chromosomes; the gene loci on the X and Y chromosomes are referred to as MIC2X and MIC2Y, respectively. It was also shown that MIC2X is located in the region Xp22.3----Xpter and MIC2Y is in the region Ypter-Yq1.1. Here, we show that MIC2X escapes X-inactivation on structurally normal and abnormal inactive human X chromosomes.
TL;DR: It is suggested that a male-determining gene on the Y has also been translocated to the X and caused maleness in the proband and perhaps in that of many other XX males.
Abstract: Of the hypotheses put forward to explain why occasional individuals with two X chromosomes are nonetheless male, the one that has attracted most attention is the possibility that one of the X chromosomes has obtained a small piece of Y chromosome which is sufficient to produce 'maleness'. This hypothesis was based primarily on the observation that in two families with XX males both fathers were Xg(a+) and both probands Xg(a-). (Xg shows X-linked dominant inheritance.) This theory holds that an anomalous X-Y interchange at meiosis in the father resulted in the paternal X chromosome's losing the Xg gene and acquiring a male-determining gene from the Y chromosome. While, for example, the frequencies of Xg phenotypes among XX males and the cytogenetic observation of a structural abnormality in one X are compatible with this hypothesis, direct evidence of it is lacking. Here we describe an XX male who expresses his father's allele for 12E7, a Y-linked marker, but fails to express his father's allele for Xg, an X-linked marker. These findings strongly suggest that anomalous X-Y interchange occurred in this case and perhaps in that of many other XX males. We suggest that a male-determining gene on the Y has also been translocated to the X and caused maleness in the proband. These results are discussed in the light of current models of X-Y chromosomal homology.
TL;DR: In imprinting, homologous chromosomes behave differently during development according to their parental origin, and this permits simpler models for the mechanism of X-inactivation, and weakens the case for evolution ofX-in activation from an earlier form of inactivation during male gametogenesis.
TL;DR: This series of clones identifies a new, conserved GAPDH‐related multigene family after characterisation of this clone, acronym OA1, showed that it maps to the short arm of the X, at Xp21 to Xp22.
Abstract: A human X chromosome-derived gene sequence which recognises an abundant, 12-kb mRNA in several cell types was previously isolated during a study to identify expressed sequences from an X chromosome recombinant library Further characterisation of this clone, acronym OA1, has shown that it maps to the short arm of the X, at Xp21 to Xp22 A 777-bp fragment of the clone which hybridizes to the 12-kb mRNA has been sequenced, and the inferred amino acid sequence shows 80% homology with the published protein sequence for human muscle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) The fragment shows even higher homology (87%) with pig muscle GAPDH The OA1 clone selects an mRNA which translates in vitro into a polypeptide of 36 K, the subunit size of GAPDH However, the X-sequence is most probably a pseudogene whose structure is consistent with it having arisen by reverse transcription of a GAPDH or GAPDH-related mRNA followed by insertion into the X chromosome The GAPDH-related portion of OA1 hybridizes to several DNA fragments in human and mouse DNA, and six fibroblast cDNA clones which cross-hybridize to OA1 identify the same genomic fragments as OA1 This series of clones identifies a new, conserved GAPDH-related multigene family
TL;DR: Analysis of DNA from males and females and from somatic cell hybrids with active or inactive X chromosomes shows that two remarkably dense clusters of CpG dinucleotides in the 3' coding sequences are hypomethylated in active G6PD genes but extensively methylated in inactive ones.
Abstract: To explore the molecular basis of X chromosome inactivation, we have examined the human locus for glucose-6-phosphate dehydro-genase (G6PD) in various human tissues. Studies of DNA from males and females and from somatic cell hybrids with active or inactive X chromosomes, show that two remarkably dense clusters of CpG dinucleotides in the 3' coding sequences are hypomethylated in active G6PD genes but extensively methylated in inactive ones. Reacquisition of G6PD activity, either spontaneous or induced by 5-azacytidine, is accompanied by demethylation of both clusters; however, the clusters remain methylated in reactivants that express HPRT but not G6PD. Our observations implicate these 3' CpG clusters in the transcription of G6PD and in maintenance of dosage compensation for X linked housekeeping genes.