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Showing papers on "Dosage compensation published in 1990"


Journal ArticleDOI
TL;DR: It is found that the human Xa in both normal male lymphocytes and hamster-human hybrids is completely unmethylated at all 120 CpG sites, whereas the Xi in normal female lymphocytes is also highly methylated, but some GCG or CGC trinucleotides partially escape methylation.
Abstract: The promoter region of the X-linked human phosphoglycerate kinase-1 (PGK-1) gene is a CpG island, similar to those often found near autosomal genes. We used ligation-mediated polymerase chain reaction (PCR) for a genomic sequencing study in which 450 bp of the human PGK-1 promoter region was analyzed for the presence of in vivo protein footprints and cytosine methylation at all CpG sites. A technique was devised to selectively visualize the DNA of the inactive X chromosome (Xi), even in the presence of the active X chromosome (Xa). We found that the human Xa in both normal male lymphocytes and hamster-human hybrids is completely unmethylated at all 120 CpG sites. In contrast, 118 of the CpG sites are methylated on the human Xi in hamster-human hybrids. The Xi in normal female lymphocytes is also highly methylated, but some GCG or CGC trinucleotides partially escape methylation; all other CpGs are fully methylated. In vivo footprinting studies with dimethylsulfate (DMS) revealed eight regions of apparent protein-DNA contacts on the Xa. Four of the footprints contained the consensus sequence of the binding site for transcription factor Sp1. The other regions include potential binding sites for transcription factors ATF, NF1, and a CCAAT-binding protein. The Xi did not show any specifically protected sequences, and with the exception of four hyperreactive sites, the in vivo DMS reactivity profile of Xi DNA was very similar to that of purified, linear Xi DNA. The implications of these findings with regard to the maintenance of methylation-free islands, X chromosome inactivation, and the chromatin structure of facultative heterochromatin are discussed.

238 citations


Journal ArticleDOI
TL;DR: The cumulative effects of all the imprinted genes are observed in androgenones (AG) and parthenogenones (PG), which reveal complementary phenotypes with respect to embryonic and extraembryonic tissues.
Abstract: Development in mammals is influenced by genome imprinting which results in differences in the expression of some homologous maternal and paternal alleles. This process, initiated in the germline, can continue following fertilization with interactions between oocyte cytoplasmic factors and the parental genomes involving modifier genes. Further epigenetic modifications may follow to render the 'imprints' heritable through subsequent cell divisions during development. Imprinting of genes can be critical for their dosage affecting embryonic growth, cell proliferation and differentiation. The cumulative effects of all the imprinted genes are observed in androgenones (AG) and parthenogenones (PG), which reveal complementary phenotypes with respect to embryonic and extraembryonic tissues. The presence of PG cells in chimeras causes growth retardation, while that of AG cells enhanced growth. AG cells apparently have a higher cell proliferation rate and, unlike PG cells, are less prone to selective elimination. However, the PG germ cells are exempt from cell selection. In chimeras, PG cells are more likely to be found in ectodermal derivatives such as epidermis and brain in contrast to AG cells which make pronounced contributions to many mesodermal derivatives such as muscle, kidney, dermis and skeleton. The presence of androgenetic cells in chimeras also results in the disproportionate elongation of the anterior-posterior axis and sometimes in the abnormal development of skeletal elements along the axis. Genetic studies high-light the influence of subsets of imprinted genes, and identify those that are critical for development.

174 citations


Journal ArticleDOI
19 Apr 1990-Nature
TL;DR: Fruitflies and nematodes show many similarities in the general organization of the gene networks that control sexual dimorphism and dosage compensation, but the underlying molecular mechanisms appear to be very different in these two species.
Abstract: Fruitflies and nematodes show many similarities in the general organization of the gene networks that control sexual dimorphism and dosage compensation. In contrast, the underlying molecular mechanisms appear to be very different in these two species. Developmental processes such as sex determination need not be strongly conserved in evolution.

154 citations


Journal ArticleDOI
TL;DR: Analysis of leukocyte DNA from a mother of two affected half-sisters revealed non-random X chromosome inactivation suggesting a possible selection against RS allele, the first evidence to support the hypothesis of an X linked mutation which is lethal in males.
Abstract: The Rett syndrome (RS) is a degenerative neurological disorder occurring exclusively in young females. The disorder is sporadic in the majority of the cases, however a few familial cases with inheritance through maternal lines have been identified. Based on these observations the condition could be due to an X chromosome mutation which is lethal in males. To explain the familial cases, a hypothesis of possible non-random X inactivation is proposed. To investigate the possibility of non-random X chromosome inactivation in RS, we carried out analysis using restriction fragment length polymorphisms (RFLPs) and methylation sensitive enzymes at the PGK and HPRT loci. The results show that there is increased incidence of non-random X chromosome inactivation in peripheral blood leukocytes in sporadic RS patient (36%), as compared to healthy controls (8%). Using brain tissue from three patients, only a random pattern was detected, although varying degrees of skewing were detected in the peripheral tissues of these patients. Analysis of leukocyte DNA from a mother of two affected half-sisters revealed non-random X chromosome inactivation suggesting a possible selection against RS allele. Additional familial cases of RS should be evaluated to determine if this observation is common to all female carriers. If non-random X chromosome inactivation occurs in all the putative "carriers," this would be the first evidence to support the hypothesis of an X linked mutation which is lethal in males.

118 citations


Journal ArticleDOI
TL;DR: It seems premature to abandon the dosage model of sex determination on the recent evidence that ZFX does not show dosage compensation, but observations on Y-ve XX males and an additional exceptional Y+ patient suggest that the ZFY locus is not essential for male differentiation and is not the primary testis determining factor.
Abstract: Clinical, chromosomal and molecular studies of a group of 15 XX males confirm the presence of two main groups. A Y+ve group of ten patients exhibit sex reversal as the result of transfer of the distal end of the short arm of the Y chromosome, including testis determining factors, to the short arm of one X-chromosome, presumably by accidental crossing-over in paternal meiosis. The ten patients have Klinefelter's syndrome but differ from XXY cases in that they are short and shown no impairment of intelligence. The four Y-ve XX males have no demonstrable Y sequences and differ from Y+ve cases in abnormality of the external genitalia and invariable gynaecomastia; in this, they more closely resemble XX true hermaphrodites than XY males. These observations on Y-ve XX males and an additional exceptional Y+ patient suggest that the ZFY locus is not essential for male differentiation and is not the primary testis determining factor. Male sex determination in sporadic, and familial Y-ve XX males and true hermaphrodites is likely to be the result of mutation in an X-linked TDF gene and its consequent escape from the constraints of X-inactivation. It seems premature to abandon the dosage model of sex determination on the recent evidence that ZFX does not show dosage compensation.

102 citations


Journal ArticleDOI
TL;DR: It is likely that regulatory mechanisms essential for early embryogenesis do not function correctly in XnX16 embryos due to activity of the extra X chromosome segment of X16.
Abstract: Matings between female mice carrying Searle's translocation, T(X;16)16H, and normal males give rise to chromosomally unbalanced zygotes with two complete sets of autosomes, one normal X chromosome and one X16 translocation chromosome (XnX16 embryos). Since X chromosome inactivation does not occur in these embryos, probably due to the lack of the inactivation center on X16, XnX16 embryos are functionally disomic for the proximal 63% of the X chromosome and trisomic for the distal segment of chromosome 16. Developmental abnormalities found in XnX16 embryos include: (1) growth retardation detected as early as stage 9, (2) continual loss of embryonic ectoderm cells either by death or by expulsion into the proamniotic cavity, (3) underdevelopment of the ectoplacental cone throughout the course of development, (4) very limited, if any, mesoderm formation, (5) failure in early organogenesis including the embryo, amnion, chorion and yolk sac. Death occurred at 10 days p.c. Since the combination of XO and trisomy 16 does not severely affect early mouse development, it is likely that regulatory mechanisms essential for early embryogenesis do not function correctly in XnX16 embryos due to activity of the extra X chromosome segment of X16.

100 citations


Book ChapterDOI
TL;DR: This chapter concentrates on the sex determination pathway in somatic cells, but it also discusses some aspects of dosage compensation and sex determination in the germ line because the three processes are in part controlled by the same genes.
Abstract: Publisher Summary This chapter presents Bridges' classic model that attempted to explain how sex is determined in Drosophil. Bridges visualized this signal as the result of two sets of counteracting elements, with the X chromosomes carrying female-determining factors and the autosomes male-determining factors. This chapter concentrates on the sex determination pathway in somatic cells, but it also discusses some aspects of dosage compensation and sex determination in the germ line because the three processes are in part controlled by the same genes. Moreover, this chapter deals with the second step from Sxl to dsx. It also explains how it might implement differential activity of Sxl. The chapter addresses the question of how dsx achieves differential expression of those genes that actually produce the sexual dimorphism at the phenotypical level.

99 citations


Journal ArticleDOI
TL;DR: Results indicate that the fl(2)d gene is needed for the sex‐specific splicing pattern of the Sxl RNA that occurs in females, thus suggesting the involvement of the fl2d gene in the positive autoregulatory pathway of SxL.
Abstract: In Drosophila melanogaster, sex determination and dosage compensation are under the control of the Sex-lethal (Sxl) gene. We have identified a gene, female-lethal-2-d (fl(2)d), located in the second chromosome, that interacts with Sxl. fl(2)d homozygous clones, induced during the larval stage of fl(2)d/+ females, develop male structures instead of female ones. fl(2)d homozygous females hypertranscribe their two X chromosomes, as measured by comparing the level of the X-linked sgs-4 transcript, which is dosage compensated, with that of the autosomal sgs-3 transcript. Thus, with respect to the processes of sex determination and dosage compensation, loss-of-function mutations at the fl(2)d and at the Sxl genes are equivalent. Moreover, fl(2)d homozygous female larvae express the Sxl transcripts characteristic of males. These results indicate that the fl(2)d gene is needed for the sex-specific splicing pattern of the Sxl RNA that occurs in females, thus suggesting the involvement of the fl(2)d gene in the positive autoregulatory pathway of Sxl.

98 citations


Journal ArticleDOI
01 Mar 1990-Genetics
TL;DR: The role of autosomal dosage compensation in understanding aneuploid syndromes and karyotype evolution in Drosophila species is discussed and a region that exerts an inverse regulatory effect on alcohol dehydrogenase activity and messenger RNA levels is revealed.
Abstract: An example of autosomal dosage compensation involving the expression of the alcohol dehydrogenase (Adh) locus is described. Flies trisomic for a quarter of the length of the left arm of chromosome two, including Adh, have diploid levels of enzyme activity and alcohol dehydrogenase messenger RNA. Subdivision of the compensating trisomic into smaller ones revealed a region that exerts an inverse regulatory effect on alcohol dehydrogenase activity and messenger RNA levels and a smaller region surrounding the structural gene that exhibits a direct gene dosage response. The two opposing effects are of sufficient magnitude that they cancel when simultaneously present resulting in the observed compensation in the larger aneuploid. An Adh promoter-white structural gene fusion construct is affected by the inverse regulatory region indicating that the effect is mediated through the Adh promoter sequences. The role of autosomal dosage compensation in understanding aneuploid syndromes and karyotype evolution in Drosophila species is discussed.

84 citations


Journal ArticleDOI
01 Jun 1990-Genomics
TL;DR: In patients and normal controls, the pattern of X inactivation varied widely from tissue to tissue and often deviated markedly from a 50:50 proportion, so deviations are likely to reflect small numbers of tissue-specific stem cells at the time of random X in activation and cannot be taken alone as evidence for selection or "nonrandom" inactivation.

71 citations


Journal ArticleDOI
TL;DR: The facts and ideas which have been discussed lead to the following synthesis and model that is based on the model developed in the previous chapter.
Abstract: SUMMARY The facts and ideas which have been discussed lead to the following synthesis and model. 1 Heteromorphic sex chromosomes evolved from a pair of homomorphic chromosomes which had an allelic difference at the sex-determining locus. 2 The first step in the evolution of sex-chromosome heteromorphism involved either a conformational or a structural difference between the homologues. A structural difference could have arisen through a rearrangement such as an inversion or a translocation. A conformational difference could have occurred if the sex-determining locus was located in a chromosomal domain which behaved as a single control unit and involved a substantial segment of the chromosome. It is assumed that any conformational difference present in somatic cells would have been maintained in meiotic prophase. 3 Lack of conformational or structural homology between the sex chromosomes led to meiotic pairing failure. Since pairing failure reduced fertility, mechanisms preventing it had a selective advantage. Meiotic inactivation (heterochromatinization) of the differential region of the X chromosome in species with heterogametic males and euchromatinization of the W in species with heterogametic females are such mechanisms, and through them the pairing problems are avoided. 4 Structural and conformational differences between the sex chromosomes in the heterogametic sex reduced recombination. In heterogametic males recombination was reduced still further by the heterochromatinization of the X chromosome, which evolved in response to selection against meiotic pairing failure. 5 Suppression of recombination resulted in an increase in the mutation rate and an increased rate of fixation of deleterious mutations in the recombination-free chromosome regions. Functional degeneration of the genetically isolated regions of the Y and W was the result. In XY males this often led to further meiotic inactivation of the differential region of the X chromosome, and in this way an evolutionary positive-feedback loop may have been established. 6 Structural degeneration (loss of material) followed functional degeneration of Y or W chromosomes either because the functionally degenerate genes had deleterious effects which made their loss a selective advantage, or because shorter chromosomes were selectively neutral and became fixed by chance. 7 The evolutionary routes to sex-chromosome heteromorphism in groups with female heterogamety are more limited than in those with male heterogamety. Oocytes are usually large and long-lived, and are likely to need the products of X- or Z-linked genes. Meiotic inactivation of these chromosomes is therefore unlikely. In the oocytes of ZW females, meiotic pairing failure is avoided through euchromatinization of the W rather than heterochromatinization of the Z chromosome. Since both chromosomes are euchromatic, recombination should occur. There is therefore no reason for the functional or structural degeneration of the W unless it is initiated by a reduction in crossing-over brought about by a structural change such as a paracentric inversion. A conformational difference between the homologues could have led to functional degeneration of the W only if meiotic pairing and recombination were uncoupled as they are in the Lepidoptera. 8 Sex-chromosome heteromorphism usually causes gene-dosage differences between males and females. In some organisms with male heterogamety, the mechanisms controlling meiotic X-inactivation in the spermatocyte were modified in ways which led to dosage compensation in the somatic cells. Since no meiotic inactivation mechanisms occur for Z chromosomes, dosage-compensation systems comparable to those found in species with male heterogamety could not evolve in species with femal heterogamety. 9 In marsupials, dosage compensation is brought about by preferential inactivation of the paternal X chromosomes in females. The general suppression of recombination observed in female marsupials could be a consequence of selection pressures resulting from preferential X-inactivation. 10 Sex-chromosome heteromorphism and the conformational changes of meiosis which are associated with it may be the reason why X chromosomes show more genomic imprinting than autosomes. The asymmetrical pattern of transmission of sex chromosomes may give parental imprinting a selective advantage. 11 Genetic changes affecting the conformation of sex chromosomes may be important causes of the sterility and inviability found in hybrids between individuals from populations which have diverged during periods of isolation.

Book ChapterDOI
TL;DR: This chapter compares and contrasts various aspects of sex determination and dosage compensation processes in Caenorhabditis elegans with their counterparts in Drosophila melanogaster and mammals, and suggests that sex determination strategies that initially appear to be quite different may not in fact be so different after all.
Abstract: Publisher Summary This chapter compares and contrasts various aspects of sex determination and dosage compensation processes in Caenorhabditis elegans with their counterparts in Drosophila melanogaster and mammals. This chapter emphasizes two points. The first is that sex determination strategies that initially appear to be quite different may not in fact be so different after all. At face value, the sex-determining mechanism of C. elegans, in which the X/A ratio serves as the primary sex-determining signal, seems extremely unlike that found in mammals, where a dominant sex chromosome (the Y chromosome in males) is the primary determinant of sex. Moreover, C. elegans can be readily interconverted from the XX hermaphrodite-XO male state to a ZW female-ZZ male state, in which sex is determined by a dominant sex chromosome (the W chromosome in females), by using a combination of dominant and recessive mutations at a single sex-determining locus. Evolutionary mechanisms by which this type of change might occur, as well as examples from other organisms in which populations have been changed from one sex-determining system to another under selective pressure, have been discussed extensively in the chapter. When sex determination is considered in a broader context, as a model for studying the fundamental processes in developmental biology, the field is enriched by the finding of such diversity because it increases the number and types of developmental strategies that may be discovered and elucidated.

Journal ArticleDOI
TL;DR: It is demonstrated that the human TIMP gene is subject to X inactivation at the level of transcription, and the usefulness of the polymerase chain reaction to study the extent of X-linked gene repression by the process of X in activation is illustrated.
Abstract: X chromosome inactivation results in the cis-limited inactivation of most, but not all, genes on one of the two X chromosomes in mammalian females. The molecular basis for inactivation is unknown. In order to examine the transcriptional activity of human X-linked genes, a series of mouse-human somatic cell hybrids under positive selection for the active or inactive human X chromosome has been created. Northern blot analysis of RNA from these hybrids showed that the human MIC2 gene, which is known to escape X inactivation, was transcribed in hybrids with either the active or inactive X chromosome. In contrast, the human TIMP gene was only transcribed in hybrids with an active human X chromosome. Further analysis using the polymerase chain reaction showed that there was at least one-hundred fold less transcription of the TIMP gene from the inactive X than from the active X chromosome. These findings demonstrate that the human TIMP gene is subject to X inactivation at the level of transcription, and illustrate the usefulness of the polymerase chain reaction to study the extent of X-linked gene repression by the process of X inactivation.

Journal ArticleDOI
01 Jan 1990-Genetics
TL;DR: Analysis of 14 new sdc-1 alleles suggests that the phenotypes resulting from the lack of sDC-1 function are an incompletely penetrant sexual transformation of XX animals toward the male fate, and increased levels of X-linked gene transcripts in XX animals, correlated with XX-specific morphological defects but not significant XX- specific lethality.
Abstract: Our previous work demonstrated that mutations in the X-linked gene sdc-1 disrupt both sex determination and dosage compensation in Caenorhabditis elegans XX animals, suggesting that sdc-1 acts at a step that is shared by the sex determination and dosage compensation pathways prior to their divergence. In this report, we extend our understanding of early events in C. elegans sex determination and dosage compensation and the role played by sdc-1 in these processes. First, our analysis of 14 new sdc-1 alleles suggests that the phenotypes resulting from the lack of sdc-1 function are (1) an incompletely penetrant sexual transformation of XX animals toward the male fate, and (2) increased levels of X-linked gene transcripts in XX animals, correlated with XX-specific morphological defects but not significant XX-specific lethality. Further, all alleles exhibit strong maternal rescue for all phenotypes assayed. Second, temperature-shift experiments suggest that sdc-1 acts during the first half of embryogenesis in determining somatic sexual phenotype, long before sexual differentiation actually takes place, and consistent with our previous proposal that sdc-1 acts at an early step in the regulatory hierarchy controlling the choice of sexual fate. Other temperature-shift experiments suggest that sdc-1 may be involved in establishing but not maintaining the XX mode of dosage compensation. Third, a genetic mosaic analysis of sdc-1 produced an unusual result: the genotypic mosaics failed to display the sdc-1 sexual transformation phenotypes. This result suggests several possible interpretations: (1) sdc-1 is expressed immediately, in the one- or two-celled embryo; (2) sdc-1 acts non-cell-autonomously, such that expression of the gene in either the AB or P1 lineage can supply sdc-1(+) function to cells of the other lineage; (3) the X/A ratio is assessed immediately, in the one- or two-celled embryo; or (4) the X/A signal directs the choice of sexual fate in a non-cell-autonomous fashion. Finally, examination of the classes of sexual phenotypes produced in sdc-1 mutant strains suggests that different cells in the organism may not choose their sexual fates independently.

Journal Article
TL;DR: The analysis presented here supports and suggests a biological explanation for peculiarities of fragile-X inheritance described by others as "clustering" and the "Sherman paradox" as consequences of a very small number of oogonial progenitor cells.
Abstract: Laird has proposed that the human fragile-X syndrome is caused by abnormal chromosome imprinting. The analysis presented here supports and extends this proposal. Using published pedigrees that include DNA polymorphism (RFLP) data, we establish that the states of the fragile-X mutation termed "imprinted" and "nonimprinted" usually can be distinguished by the level of cytogenetic expression of the fragile-X chromosome. This information is then used to assess the state of the fragile-X allele in carrier progeny of individual women who inherited a nonimprinted fragile-X chromosome. From this assessment, an estimate is made of the frequency, in individual women, of primary oocytes with an imprinted fragile-X chromosome. The results of this analysis provide additional support for the specific model in which chromosome imprinting occurs in a female in, on average, half of her primary oocytes. This is the expected frequency if X-chromosome inactivation is the initial step in the imprinting of the mutant fragile-X allele. Moreover, this analysis suggests a biological explanation for peculiarities of fragile-X inheritance described by others as "clustering" and the "Sherman paradox." We interpret these peculiarities as consequences of a very small number of oogonial progenitor cells. Two progenitor cells for oogonia is the best integer estimate of the number of such cells at the time of the initial event that leads to chromosome imprinting.

Journal Article
TL;DR: The population genetic consequences of the model of Laird (Genetics 117:587-599, 1987) in which the fragile-X syndrome is caused by "imprinting" of a mutant chromosome are examined.
Abstract: We have examined the population genetic consequences of the model of Laird (Genetics 117:587-599, 1987) in which the fragile-X syndrome is caused by "imprinting" of a mutant chromosome. The imprinting event in this model results from a block to reactivation of an inactive X chromosome prior to oogenesis. If it is assumed that males carrying the imprinted chromosome never reproduce, the frequencies of females and males carrying the imprinted chromosome are expected to be equal. When a mutation-selection balance is established, there are expected to be somewhat more than twice as many females carrying the nonimprinted fragile X as carry the imprinted fragile-X chromosome, the excess depending on the fertility of fragile-X females. Nonpenetrant (transmitting) males, i.e., those with the nonimprinted fragile-X chromosome, are expected to be present at about the same frequency as are males with the syndrome. More than one-third of the nonimprinted chromosomes in the population are expected to be newly arisen in each generation. We have considered possible alternatives to the model of a mutation-selection balance. Nonimprinted carrier females would need to have 100% fertility excess to avoid postulating a high mutation rate to account for the very high prevalence of the syndrome.

Journal Article
TL;DR: Allelic exclusion imposed by imprinting might be based on the heritable DNA methylation of the regulatory regions of silent genes, and this provides a basis for genomic imprinting.
Abstract: In diploid cells, allelic exclusion reduces genes to functional haploidy, because only one of two alleles is active. It is best known in cells producing immunoglobulins, but other examples also exist. X-chromosome inactivation in female mammals is related to allelic exclusion, but in this case the dosage compensation mechanism extends to the whole chromosome. Functional hemizygosity in some mammalian cell lines is probably also due to allelic exclusion, where one autosomal allele is active and the other is methylated and inactive. In early development, it may be important to have only one functional copy of specific regulatory genes. If one considers the possible mechanisms whereby genes are switched from an active to an inactive form, or vice versa , complications arise if the same type of switch operates in two homologous chromosomes segregating independently at mitosis. This complication is avoided if one of the genes is totally inactive. It is therefore suggested that important regulatory genes are subject to allelic exclusion and that this provides a basis for genomic imprinting. Male or female gametes complement in the zygote, because they may have different inactive genes, and the active allele in each case is then functionally haploid in the zygote and developing embryo. These haploid genes would be those involved in critical switches of gene activity during the developmental process. Allelic exclusion imposed by imprinting might be based on the heritable DNA methylation of the regulatory regions of silent genes.

Journal ArticleDOI
TL;DR: In this paper, the authors studied the phenomenon of inactivation in two Y centromeres, having as a control genetically identical active and inactive Y centromres, and concluded that, in the case of the isochromosome, a true deletion of centromeric chromatin is responsible for its stability, whereas in the second case, stability of the dicentric (X;Y) is the result of centromeere chromatin modification.
Abstract: Stable dicentric chromosomes behave as monocentrics because one of the centromeres is inactive. The cause of centromere inactivation is unknown; changes in centromere chromatin conformation and loss of centromeric DNA elements have been proposed as possible mechanisms. We studied the phenomenon of inactivation in two Y centromeres, having as a control genetically identical active Y centromeres. The two cases have the following karyotypes: 45,X/46,X,i(Y)(q12) and 46,XY/ 47,XY,+t(X;Y)(p22.3;p11.3). The analysis of the behaviour of the active and inactive Y chromosome centromeres after Da-Dapi staining, CREST immunofluorescence, and in situ hybridization with centromeric probes leads us to conclude that, in the case of the isochromosome, a true deletion of centromeric chromatin is responsible for its stability, whereas in the second case, stability of the dicentric (X;Y) is the result of centromere chromatin modification.

Journal ArticleDOI
TL;DR: The functional locus for α-amylase (Amy) inDrosophila miranda is in the evolutionarily new X2 chromosome, and on the diet with glucose,Amy expression was repressed in both WT 10 and S 204 larvae and male larvae of S 204 displayed dosage compensation for amylase activity.
Abstract: The functional locus for α-amylase (Amy) inDrosophila miranda is in the evolutionarily new X2 chromosome. X2 evolved from an autosome in response to an ancestral autosome-Y translocation that gave rise to the “neo-Y” chromosome of this species. Y-linkedAmy, if still present in the ancestrally translocated element, is unexpressed. Dosage compensation for amylase activity was examined in larvae of the S 204 strain. Since dietary glucose is known to repressAmy expression inDrosophila melanogaster, dosage compensation of amylase activity in male larvae ofD. miranda was tested by rearing larvae of both sexes on yeast diets with or without a glucose supplement. The WT 10 strain ofDrosophila persimilis, a sibling species in whichAmy is autosomally linked, was used as a reference for tests of amylase activity differences between the sexes. On the diet with glucose,Amy expression was repressed in both WT 10 and S 204 larvae and male larvae of S 204 displayed dosage compensation for amylase activity. On the nonrepressing diet consisting of yeast alone, S 204 continued to display dosage compensation.

Journal ArticleDOI
TL;DR: Red cell gene dosage studies using adenosine deaminase (ADA) have confirmed that the proposita is trisomic for 20q and suggest that there is incomplete inactivation of the autosomal portion of the consistently late-replicating abnormal X.
Abstract: A first case of "pure" trisomy 20q (q11.2-qter) is described in a female child with minor anomalies and developmental delay. This resulted from the inheritance, from a carrier mother, of an abnormal X chromosome: der (X)t(X;20)(q28;q11.2). Involvement of other autosomes has complicated the interpretation of the phenotypic effect of trisomy 20q in previously published case reports. Red cell gene dosage studies using adenosine deaminase (ADA) have confirmed that the proposita is trisomic for 20q. Taken together with RBG staining studies, these results suggest that there is incomplete inactivation, if any, of the autosomal portion of the consistently late-replicating abnormal X. Unexpectedly, ADA gene dosage results in the carrier mother showed a level of gene expression about half that of normal controls.

Journal Article
01 Jul 1990-Oncogene
TL;DR: A specific translocation between chromosomes X and 18 was identified in synovial sarcomas and the position of the breakpoint lies proximal to GAPD1, ARAF1 and TIMP and distal to DXS255 and DXS146.
Abstract: A specific translocation between chromosomes X and 18 was identified in synovial sarcomas. From a girl with synovial sarcoma, we isolated two clones with t(X; 18)(p11.2; q11.2) and which had lost the normal X chromosome. Southern blot analysis of DNA from the tumor, the patient and her parents demonstrated that the normal X chromosome, lost in the tumor, was the paternal one. A somatic hybrid cell line was established by fusing tumor cells (after passages on athymic mice) to an HPRT deficient hamster cell line. By cytogenetic, in situ hybridization and molecular analysis, it was found to contain the derivative (X) chromosome in the absence of the der (18) chromosome. To determine the position of the breakpoint on the X chromosome, Southern blots of DNA from this hybrid were hybridized to [32P]-labelled X chromosome probes. DXS146 and DXS255 were retained in the hybrid cell line whereas GAPDP1, the ARAF1 and TIMP proto-oncogenes were not present, indicating that the breakpoint lies proximal to GAPD1, ARAF1 and TIMP and distal to DXS255 and DXS146. Results obtained from other authors are compared. Further studies will be necessary to determine the extent of variation of the breakpoint in different tumors.

BookDOI
01 Jan 1990
TL;DR: "Novel chromosome techniques by flow cytometry, and mapping of structural have become an integral component of clinical ly and functionally distinct domains on metaphase and molecular genetic methodologies."
Abstract: These are exciting days in biology; chromosome such functional attributes of chromosomes as research is no exception. Twenty years ago when replication, dosage compensation and cellular Caspersson and coworkers showed that meta response to DNA lesions. It is only recently that a phase chromosomes are structurally not homo molecular view of the meiotic cell division is geneous through their length, a new world was beginning to emerge: chapter ten refers to human in the offing. Application of various molecular meiosis and the next to molecular events in techniques in chromosome research has subse meiotic prophase in the baker's yeast. Another quently narrowed down the gap between the chapter is on aneuploidy in man and the Djungarian levels of microscopic and molecular understand hamster. The role of chromosome rearrange ing of chromosome organization. While complex ments and oncogenes in malignancy and the ities of older questions of chromosome/ parallelism between the neoplastic and phy chromatin organization are being understood, logenetic chromosomal alterations are discussed newer dimensions and perspectives have been in the next two chapters. Recent introduction of gained with respect to their structure and func potentially useful methods of chromosome isola tions. Even more, novel chromosome techniques tion by flow cytometry, and mapping of structural have become an integral component of clinical ly and functionally distinct domains on metaphase and molecular genetic methodologies."

Journal ArticleDOI
TL;DR: The first practical application of a genetic scheme devised for the purpose of obtaining large quantities of embryos of a specific sex is reported, establishing that the steady-state levels of transcripts of X-linked genes are the same in early male and female embryos.
Abstract: We report the first practical application of a genetic scheme devised for the purpose of obtaining large quantities of embryos of a specific sex. The scheme, which is based on the meiotic drive system Segregation Distorter, results in the production of populations of zygotes that are almost exclusively of one sex. We have used this scheme to determine that the steady-state levels of transcripts of X-linked genes are the same in early male and female embryos, establishing that these genes are dosage compensated.

Journal ArticleDOI
01 Dec 1990-Genetica
TL;DR: The replication study has shown that there is no dosage compensation for the Z chromosome in (homogametic) males, and that genetic inactivation precedes chromosomal mutations in non-vivipara lacertid evolution of the odd sex chromosome is suggested.
Abstract: Even if the common lizardLacerta vivipara and endemicLacerta andreanskyi from Moroccan Grand Atlas have the same mother species, the two species are definitely not closely related in present-day nature, whereL. vivipara stands at variance from all other lacertids in terms of cytogenetics. The use of replication banding, C-bands and R-bands has allowed for the identification of all chromosome pairs and two sex chromosomes inL. andreanskyi. Its karyotype is typical of Lacertidae. The W chromosome, characterized by late replication, is nevertheless of a type previously unknown in the family. The comparison of Z and W chromosomes by different methods of chromosome banding indicates little homology between them, if any. The replication study has shown that there is no dosage compensation for the Z chromosome in (homogametic) males. That genetic inactivation precedes chromosomal mutations in non-vivipara lacertid evolution of the odd sex chromosome is suggested.

Journal ArticleDOI
TL;DR: An intriguing and unexplained finding is that mutations and X‐chromosome duplications that elevate X‐linked gene expression also feminize triploid males.
Abstract: The signal for sex determination in the nematode Caenorhabditis elegans is the ratio between the number of X chromosomes and the number of sets of autosomes (the X/A ratio). Animals with an X/A ratio of 0.67 (a triploid with two X chromosomes) or less are males. Animals with an X/A ratio of 0.75 or more are hermaphrodites. Thus, diploid males have one X chromosome and diploid hermaphrodites have two X chromosomes. However, the difference in X-chromosome number between the sexes is not reflected in general levels of X-linked gene expression because of the phenomenon of dosage compensation. In dosage compensation, X-linked gene expression appears to be 'turned down' in 2X animals to the 1X level of expression. An intriguing and unexplained finding is that mutations and X-chromosome duplications that elevate X-linked gene expression also feminize triploid males. One way that this relationship between sex determination and X-linked gene expression may be operating is discussed.