Showing papers on "X chromosome published in 1974"
TL;DR: In this article, position effect variegation has been studied in female mice heterozygous for the flecked X-autosome translocation, T(7; X)Ct, and found that early occurring events do not lay down fixed programs of gene suppression, as proposed for Drosophila, but that, like the lateroccurring events, they represent the reactivation of previously inactivated loci.
Abstract: Position effect variegation has been studied in female mice heterozygous for the flecked X-autosome translocation, T(7; X)Ct Some of these carried the spotting gene (s) which clarifies the variegated patterns Others carried a second X-autosome translocation, T(X; 16)16H, which suppresses the randomness of X-chromosome activityIt was found the position effect variegation stems primarily from early occurring events which lead to the formation of clones of cells with different phenotypes In this respect the phenomenon appears to parallel that found in Drosophila However, in the mouse, late-occurring events are also found which can only be readily accounted for by the reactivation of previously inactive loci They occur, not only during foetal development, but throughout the life-time of the animals and in a manner which suggests they derive from a progressive retreat of the inactivating influence of the heterochromatic X chromosome back along the attached autosome towards the breakpoint It is proposed that the early occurring events do not lay down fixed programmes of gene suppression, as proposed for Drosophila, but that, like the later-occurring events, they represent the reactivation of previously inactivated loci The possibility that this might also be true for Drosophila is discussedThe study also provided evidence favouring the view that the X-chromosome controlling element, Xce, modifies the heterozygous phenotypes of X-linked genes by biasing the randomness of the X-inactivation process, rather than by operating through cell selection mechanisms The data also support and extend Mintz's (1967) concept of pigment pattern differentiation
188 citations
TL;DR: The phenotypic effects of monosomy, disomy and trisomy for different parts of Xp and Xq are discussed and the existence of an inactivation center without which an X chromosome cannot be inactivated is assumed.
Abstract: Abnormal human X chromosomes, their origin, phenotypic effects, and especially their inactivation are reviewed. In cases of balanced reciprocal X-autosomal translocations (Table 2), almost always the normal X is inactivated. Most of such patients suffer from gonadal dysgenesis, which might be caused either by functional hemizygosity for a recessive gene or by a position effect resulting from a rearrangement involving a certain region of Xq. In cases with 46 chromosomes and an unbalanced X-X translocation, the translocation chromosome is inactivated; in most such patients, an X0 cell line is also present (Table 3). Some of the possible modes of origin of such translocations are presented in Fig. 1; these also explain the occurrence of the X0 cell lines. In patients with 46 chromosomes and an unbalanced X-autosomal translocation, the whole translocation chromosome seems to be inactivated, if the autosomal segment is attached to Xp. If on the other hand the segment is, attached to Xq, inactivation seems to be limited to the X part (Fig. 3). There are reasons for assuming the existence of an inactivation center without which an X chromosome cannot be inactivated. This center would be located on the proximal part of Xq. (Abnormal chromosomes with two such centers tend to form bipartite Barr bodies.) If 2 X chromosomes possess an inactivation center each, they would originally be inactivated at random, it then being left to selection to determine the final frequencies of the cell lines with different inactivation patterns. The phenotypic effects of monosomy, disomy and trisomy for different parts of Xp and Xq are discussed (Fig. 3).
119 citations
TL;DR: The two X chromosomes of female mouse cells in early cleavage stages showed the same characteristic banding pattern as that observed in the X chromosome from adult male fibroblasts, and it was not until the 9th day of gestation that the late-labeling X predominated, as in adult cells.
114 citations
Journal Article•
111 citations
TL;DR: X chromatin in man condenses around a center which is situated on Xq at a short distance from the centromere, so that chromosomes lacking the center would form no Barr body and therefore presumably would not be inactivated, thus leaving the cell severely unbalanced.
Abstract: The following hypothesis is put forward: X chromatin in man condenses around a center which is situated on Xq at a short distance from the centromere. The hypothesis is based on, and explains, two classes of observations. (1) Abnormal X chromosomes that have the assumed center in duplicate form bipartite Barr bodies in part of the cells. The frequency of bipartite bodies and the distance between the two parts seem to be determined by the distance between the postulated centers. (2) A large number of variously abnormal X chromosomes have been described. Almost all of them possess the postulated center and it seems possible that the very few apparent exceptions represent misidentifications of chromosome Xq — as isochromosome i(Xp). According to the hypothesis, chromosomes lacking the center would form no Barr body and therefore presumably would not be inactivated, thus leaving the cell severely unbalanced. Furthermore, absence of the center might interfere with the viability of the chromosome itself.
82 citations
TL;DR: It is suggested that the inactivation seen in somatic cells had evolved from inactivation of both sex chromosomes in male gametogenesis, a phenomenon that is general in gametes of the heterogametic sex of many species.
Abstract: IT is now well established that in the somatic cells of mammals only a single X chromosome is active in coding for proteins, no matter how many are present1,2, but the mechanism and evolutionary origin of this phenomenon still remain unsolved problems Cooper3 suggested that the random inactivation of X chromosomes derived from either parent in eutherian mammals had evolved from a more primitive inactivation of the paternally derived X chromosome as seen in marsupials, and a possible mechanism for this evolution has been put forward4 Lifschytz and Lindsley5 further suggested that the inactivation seen in somatic cells had evolved from inactivation of both sex chromosomes in male gametogenesis, a phenomenon that is general in gametes of the heterogametic sex of many species
78 citations
TL;DR: There exists a difference in radio-sensitivity between the two sexes and the Y chromosome is found to be more resistant and the breaks are preferentially localized in the pericentromeric heterochromatin of the X chromosome and of the autosomes.
Abstract: A technique has been perfected for enabling good microscope preparations to be obtained from the larval ganglia of Drosophila melanogaster . This system was then tested with X-rays and an extensive series of data was obtained on the chromosome aberrations induced in the various stages of the cell cycle.—The analysis of the results obtained offers the following points of interest: (1) There exists a difference in radio-sensitivity between the two sexes. The females constantly display a greater frequency of both chromosome and chromatid aberrations. They also display a greater frequency of spontaneous aberrations. (2) In both sexes the overall chromosome damage is greater in cells irradiated in stages G2 and G1. These two peaks of greater radiosensitivity are produced by a high frequency of terminal deletions and chromatid exchanges and by a high frequency of dicentrics, respectively. (3) The aberrations are not distributed at random among the various chromosomes. On the average, the Y chromosome is found to be more resistant and the breaks are preferentially localized in the pericentromeric heterochromatin of the X chromosome and of the autosomes. (4) Somatic pairing influences the frequency and type of the chromosome aberrations induced. In this system, such an arrangement of the chromosomes results in a high frequency of exchanges and dicentrics between homologous chromosomes and a low frequency of scorable translocations. Moreover, somatic pairing, probably by preventing the formation of looped regions in the interphase chromosomes, results in the almost total absence of intrachanges at both chromosome and chromatid level.
71 citations
TL;DR: Crosses employing either bio1 or bio69-substituted phage strains indicate that the bio-associated hot spot activity occurs in the presence of DNA synthesis, but is dependent on a functional host recB gene.
Abstract: In order to survey the distribution along the bacteriophage X chromosome of Rec-mediated recombination events, crosses are performed using conditions which block essentially all DNA synthesis. One parent is density-labeled and carries a genetic marker in the left terminal X gene (A), while the other parent is unlabeled and carries a genetic marker in the right terminal X gene (R). Both parents are deleted for the X recombination genes int and red, together with other recombination-associated genes, by virtue of either (1) a pure deletion or (2) a bio insertion-deletion. The distribution in a cesium density gradient of the resulting A+R+ recombinant phage reflects the chromosomal distribution of the recombination events which gave rise to those phage. Crosses employing either of two different pure deletion phage strains exhibit recombinational hot spot activity located near the right end of the X chromosome, between the cl and R genes. This hot spot activity persists when unlimited DNA synthesis is allowed. Crosses employing bioi-substituted phage strains exhibit recombinational hot spot activity located to the right of the middle of the chromosome and to the left of the cl gene. Crosses employing either bioi or bio69-substituted phage strains indicate that the bio-associated hot spot activity occurs in the presence of DNA synthesis, but is dependent on a functional host recB gene. HE bacteriophage X chromosome is subject to the action of three genetic reTcombination system: Int, which is site specific for the X attachment locus, and Red and Rec, which are generalized (SINGER 1971). The products of the phage genes int, reda and redB are essential components of their respective recombination systems (see Figure 1). The reda gene product-X exonucleasevery likely is involved directly in the recombinatioc process; the role of the redP gene product-+ protein-is unknown (RADDING 1973). Similarly, the recBrecC DNase of E. coli appears to be a central component of the Rec recombination system (CLARK 1973). However, residual recombination typically occurs in recB- or recC- hosts. By way of contrast, loss of the recA gene product blocks all host-mediated recombination; the function of the recA gene is unknown. The Red and Rec recombination systems presumably are capable of mediating recombination events essentially anywhere on the chromosome. Moreover. the
69 citations
TL;DR: A comparison of the Giemsa-banding patterns of the X chromosomes in various mammalian species including man indicates that two major bands (A and B), which are resistant to trypsin and urea-treatments, are always present irrespective of the gross morphology of theX chromosomes.
Abstract: A comparison of the Giemsa-banding patterns of the X chromosomes in various mammalian species including man indicates that two major bands (A and B), which are resistant to trypsin and urea-treatments, are always present irrespective of the gross morphology of the X chromosomes. This is true in all mammalian species with the "original or standard type" X chromosomes (5–6% of the haploid genome) thus far analyzed. In the unusually large-sized X chromosomes the extra chromosomal material may be due either to the addition of genetically inert constitutive heterochromatin or to an X-autosome translocation. In these X chromosomes two major bands are present in the actual X-chromosome segment. Our data on C and G band patterns also support Ohno's hypothesis that the mammalian X chromosome is extremely conservative in its genetic content, in spite of its cytogenetic variability.
68 citations
TL;DR: A Giemsa C-banding technique applied to the mosquito, Aedes aegypti, has revealed a distinctive banding pattern which is described as a reliable means of distinguishing between the morphologically similar X and Y chromosomes during all stages of mitosis and meiosis.
Abstract: A Giemsa C-banding technique applied to the mosquito, Aedes aegypti, has revealed a distinctive banding pattern which is described as a reliable means of distinguishing between the morphologically similar X and Y chromosomes during all stages of mitosis and meiosis. The essential difference is that the Y chromosome, unlike the X and the autosomes, is not C-banded in the centromere region. An intercalary band is also present in one arm of all X chromosomes and some Y chromosomes. The distribution of these cytological markers throughout meiosis indicates that the sex locus occurs somewhere within a pericentric region, the minimum extent of which includes both the intercalary band and the centromere.
63 citations
TL;DR: A method of mapping genes which specify enzymes without the necessity of obtaining genetic variants has been explored, choosing three enzymes whose structural genes have known genetic positions to see if the relationship between gene dosage and enzyme activity could be used as a tool in cytological localization.
Abstract: A method of mapping genes which specify enzymes without the necessity of obtaining genetic variants has been explored. Three enzymes whose structural genes have known genetic positions were chosen to see if the relationship between gene dosage and enzyme activity could be used as a tool in cytological localization. Zw, the gene specifying G6PD, is located in the X chromosome region, 18D-18F. The structural gene for 6PGD, Pgd, maps in the X chromosome bands 2C1-2E1. Idh-NADP, the gene which specifies IDH-NADP, is found on the third chromosome, in bands 66B-67C.
TL;DR: Following the proportion of Tfm cells in the kidneys of heterozygotes confirms that the variegation seen of the locus Blo in the coat is matched in inner tissues, and reinforces the conclusion that the O hv mutation is directly concerned in the X-activation process.
TL;DR: The well-established relevance of familial and evidently genetic factors for breast cancer in women may be generalized to all individuals whose chromosome complements include two X chromosomes, so that an individual with a masculine phenotype may face the same risk as his sisters who lack a Y chromosome.
Abstract: The well-established relevance of familial and evidently genetic factors for breast cancer in women may be generalized to all individuals whose chromosome complements include two X chromosomes. Thus, an individual with a masculine phenotype, whose chromosome complement includes a Y chromosome as well as two X chromosomes may face the same risk as his sisters who lack a Y chromosome. The familial (genetic?) factor for cancer diathesis determines a relatively high risk for breast cancer in an individual with two X chromosomes. The familial factor for cancer diathesis is transmitted to and through individuals of both sexes. The usually sex-limited (ie, to females) manifestations of the relevant familial factor is evidently not directly related to gender but rather to interaction with an effect of the occurrence of two X chromosomes. Further medical genetic studies of Klinefelter patients and their families seem warranted in order to better appraise cancer epidemiology. ( JAMA 229:809-811, 1974)
TL;DR: It seems that the occurrence of a nucleolus organizer on the translocated chromosome 15t presumably plays a role in the causal mechanism of the loose X-15t CH association, and some circumstantial evidence indicates the adverse effect of the observed tight CH attachment on the course of spermatogenesis.
Abstract: A nonrandom association is described between chromosome No. 15, which is involved in the T(14;15)6Ca translocation, and the X chromosome in diakinesis/ metaphase I plates of the male mouse. The tight attachment of centromeric heterochromatin (CH) regions of chromosomes X and 15 is predominantly found in those primary spermatocytes in which the distance between the homologous CH regions of the No. 15s exceeds some critical value. The rule holds true for both T6 homozygotes (i.e., for those of their primary spermatocytes displaying two 15t univalents) and T6 heterozygotes (i.e., for translocation configurations “III + I” and certain types of “chain-of-four” quadrivalents). The tight X-15 CH association is highly specific, since out of 1540 primary spermatocytes of the T6 heterozygotes, only 3 showed the tight X-14 CH association. In contrast to the tight CH attachment, the frequency of loose X-15 chromosome association does not show dependence upon the centromere separation of the No. 15s. The nature of the described CH association remains to be clarified; for the present, it seems that the occurrence of a nucleolus organizer on the translocated chromosome 15t presumably plays a role in the causal mechanism of the loose X-15t CH association. Some circumstantial evidence indicates the adverse effect of the observed tight CH attachment on the course of spermatogenesis.
TL;DR: Using gyandromorphs generated by mit, a morphogenetic fate map, placing the origins of 40 cuticular structures on the blastoderm surface, has been constructed and is consistent with embryological data and with the two other fate maps generated in different ways.
Abstract: A new mutant, mit (mitotic loss inducer), is described. The mutant is recessive and maternal in action, producing gynandromorphs and haplo-4 mosaics among the progeny of homozygous mit females. Mosaic loss of maternal or paternal chromosomes can occur. The probabilities of either maternal or paternal X chromosome loss are equal. mit has been mapped to approximately 57 on the standard X chromosome map.—Using gyandromorphs generated by mit, a morphogenetic fate map, placing the origins of 40 cuticular structures on the blastoderm surface, has been constructed. This fate map is consistent with embryological data and with the two other fate maps generated in different ways.
TL;DR: The X chromosome of Drosophila provides a unique system for the study of modulation of eukaryotic gene activity.
Abstract: The X chromosome of Drosophila provides a unique system for the study of modulation of eukaryotic gene activity.
TL;DR: The lod-scores of two families with Becker muscular dystrophy (BMD) informative for the G6PD locus together with those of one family previously studied by Emery, Smith, and Sanger (1969) suggest that the BMD locus could be at a measurable distance from this cluster.
Abstract: Six families in which Duchenne muscular dystrophy (DMD) and G6PD or deutan colour blindness are segregating are reported. The sum of the lod-scores of these families together with three published previously indicates that the DMD locus is far from the G6PD:deutan cluster. The lod-scores of two families with Becker muscular dystrophy (BMD) informative for the G6PD locus together with those of one family previously studied by Emery, Smith, and Sanger (1969) suggest that the BMD locus could be at a measurable distance from this cluster. The maximum likelihood estimate of the recombination fraction is 0·27 and the 90% confidence limits are 0·17 and 0·40. This difference in linkage estimates for DMD and BMD suggests that the BMD and the DMD genes are located at two different loci on the X chromosome. Five more families with DMD and two with BMD informative for Xg blood groups support the conclusion of other authors that there is no hint of linkage between the loci for Xg and for the X-linked forms of muscular dystrophy.
TL;DR: It is indicated that a mechanism for dosage compensation is operative in both arms of the X chromosome of these two species.
Abstract: We have investigated the occurrence of dosage compensation in D. willistoni and D. pseudoobscura, two species whose X chromosome is metacentric with one arm homologous to the X and the other homologous to the left arm of chromosome 3 of D. melanogaster. Crude extracts were assayed for isocitrate dehydrogenase (XR), glucose-6-phosphate dehydrogenase (XL?), 6-phosphogluconate dehydrogenase (XL?), and alpha-glycerophosphate dehydrogenase (chromosome 2) in D. willistoni, and for esterase-5 (XR), glucose-6-phosphate dehydrogenase (XL?), 6-phosphogluconate dehydrogenase (XL?) and amylase (chromosome 3) in D. pseudoobscura. Our results indicate that a mechanism for dosage compensation is operative in both arms of the X chromosome of these two species.
TL;DR: An autosomal euchromatic maternal-effect mutant, abo (= abnormal oocyte), interacts with, or regulates the activity of, the heterochromatin of the sex chromosomes of Drosophila melanogaster, and it is shown that this interaction or regulation with the X chromosome involves a specificheterochromatic locus or small region that maps to the distal penultimate one-eighth of the basal X-chromosome heterochrome segment.
Abstract: An autosomal euchromatic maternal-effect mutant, abo (= abnormal oocyte), interacts with, or regulates the activity of, the heterochromatin of the sex chromosomes of Drosophila melanogaster. It is shown that this interaction or regulation with the X chromosome involves a specific heterochromatic locus or small region that maps to the distal penultimate one-eighth of the basal X-chromosome heterochromatic segment.
TL;DR: Gene differences between these two chromosome arrangements can be explained due to differential natural selection of alleles in the Standard and Sex Ratio arrangments.
Abstract: The Standard and Sex Ratio gene arrangements of the X chromosome of D. pseudobscura differ from each other in allele frequencies at the four X chromosome loci, esterase-5, adult acid phosphatase-6, phosphoglucomutase-1 and octanol dehydrogenase-3. The Standard arrangement which is the common arrangement in all populations is polymorphic at these loci in varying degrees, the geographically less widespread Sex Ratio arrangement has little polymorphism and is genically predominantly E-51.04 AP-6- Pgm11.0 ODH-31.0. The Sex Ratio arrangement from different populations is alike at all of the four loci, the Standard arrangement shows some gene frequency differences among populations. The Standard and Sex Ratio arrangements differ from each other by three inversions which suggests that the two arrangements are "old". Gene differences between these two chromosome arrangements can be explained due to differential natural selection of alleles in the Standard and Sex Ratio arrangments.—The order and percent recombination among these four loci in the Standard arrangement are: E-5—.294—AP-6—.335—Pgm-1—.024—ODH-3. The Standard X chromosomes from four different wild populations were analyzed for evidence of linkage disequilibrium between pairs of loci at these four loci. No evidence of linkage disequilibrium between pairs of loci was obtained. However, when linkages involving simultaneously three loci, E-5, AP-6 and Pgm-1 are considered, then significant departure from linkage equilibrium is observed.
Journal Article•
TL;DR: A working hypothesis is suggested according to which the X choromsome is inactivated during a critical stage of spermatogenesis in all male heterogametic organisms, as the inactivation is an essential control and not a compensatory step, leading to dominant male sterility.
Abstract: INACTIVATION of chromosomal elements is a process which takes place in various organisms, cell types, and cell cycle stages. The reasons for chromosome inactivation, which is superimposed on the more specific level of gene control, are different for the various systems. Dosage compensation in female mammals us. mitotic chromosome shut-off are the extreme cases. Since in many systems every chromosome may be in an active or inactive form, it is reasonable to assume, for the time being, that the molecular mechanism in different organisms is similar, thus justifying generalization. The role and behaviour of sex chromosomes during gametogenesis provide a striking example of differentiation of chromosomal elements and by inference reflect chromosome function. Precocious inactiviation of the X chromosome during seprmatogenesis together with activation of fertility factors on the Y in some organisms are of particular interest. In view of cytological and genetic observations we suggest a working hypothesis according to which the X choromsome is inactivated during a critical stage of spermatogenesis in all male heterogametic organisms. As the inactivation is an essential control and not a compensatory step, any interference with this process will change the developmental course of the spermatocyte leading to dominant male sterility (LIFSCHYTZ and LINDSEY 1972). In the course of this paper, the observations that support or lead to this view will be presented. Several experimental approaches we have undertaken to study further the genetics of the phenomenon, as well as its relation to Y chromsome activation, will be discussed.
TL;DR: Several methylated components in Drosophila rRNA also occur in rRNA from HeLa cells and yeast, which suggests that certain features of rRNA structure involving methylated nucleotides may be highly conserved in eukaryotic evolution.
TL;DR: Normal male development was found in a man with a proven deletion of the long arms of the Y chromosome, and this study offers additional proof that all, or most, of theLong arms ofThe Y chromosome are not primarily concerned with the determination of male sexual characteristics.
Abstract: Normal male development was found in a man with a proven deletion of the long arms of the Y chromosome. The only phenotypic effect was on his build. This study offers additional proof that all, or most of the long arms of the Y chromosome are not primarily concerned with the determination of male sexual characteristics.
Journal Article•
TL;DR: The differential replication revealed in the autoradiograms is interpreted as a consequence of the polytene structure in giant chromosomes.
Abstract: Replication patterns of the X chromosomes and autosomes in D. melanogaster male and female larvae during the discontinuously labeled initial and end phases of DNA synthesis were compared. In female larvae X and autosomes behaved correspondingly during all the replication stages. In males, however, the X chromosome shows a differential replication behavior from that of the autosomes already during the discontinuously labeled initial stage.—In those nuclei of both sexes, in which the autosomes correspond in their initial replication patterns, significantly more labeled regions are to be found over the male X than over the female X. The complementary behavior during the end phases (Berendes, 1966), i.e. the reverse of that above, leads to an earlier completion of the replication cycle in most of the labeled regions of the male X chromosome. The differential replication revealed in the autoradiograms is interpreted as a consequence of the polytene structure in giant chromosomes.
TL;DR: Both cell lines show characteristics that are of value for the study of mammalian cell genetics, and CHW-1102 represents a useful addition to the stock of mutant mammalian cell lines.
Abstract: A mutant Chinese hamster cell line was selected from wild-type CHW cells in 30 µg/ml 8-azaguanine, after exposure for 2 h to 10–3 M methyl methanesulphonate. This line was subsequently cloned and one clone, isolated in 10 µg/ml 8-azaguanine (CHW-1102), was selected for further study. CHW-1102 showed stability of resistance to 8-azaguanine after six months of growth in nonselective medium and an LD50 to 8-azaguanine of between 10 and 20 µg/ml, compared to 2.5 µg/ml for the wild-type CHW cell line. The doubling time in culture was found to be 13 h, compared to a doubling time of 12 h for CHW. Biochemical studies showed that the mutant cell line CHW-1102 had a specific activity of HPRT of about 1–2 nmol/mg protein per hour compared to a specific activity of the wild type of 200 nmol/mg protein per hour. The spontaneous reversion rate from 8-azaguanine resistance to 8-azaguanine sensitivity was 4.23 × 10–8/locus per generation. Both the parental line (CHW) and the mutant (CHW-1102) have a modal chromosome number of 22 and a relatively stable karyotype. Both lines show some chromosome rearrangement and, in particular, the presence of one long acrocentric marker chromosome, which consists largely of material from chromosomes 6 and 8. Much of the distal part of the long arm of the X chromosome, which is heterochromatic, has been lost in both CHW and CHW-1102. So far as can be determined, no autosomal material, except perhaps the paracentromeric region of chromosome 6, is missing in CHW-1102, although even this material may be represented by a small marker chromosome M2. Both cell lines show characteristics that are of value for the study of mammalian cell genetics, and CHW-1102 represents a useful addition to the stock of mutant mammalian cell lines.