Showing papers on "X chromosome published in 1972"
TL;DR: The review considers information from mammalian embryology relevant to X‐chromosome inactivation, and from X‐inactivation relevant to mammalian embryologists, to derive conclusions about inactivation and its role in embryology.
Abstract: Summary
1. The review considers information from mammalian embryology relevant to X-chromosome inactivation, and from X-inactivation relevant to mammalian embryology.
2. Properties of the inactive-X, by which it may be recognized are: sex chromatin, heteropycnosis, late replication and the absence of gene product. Each of these has advantages and disadvantages in particular circumstances. In some species the X carries constitutive heterochromatin, which must be distinguished from the facultative region.
3. The time of X-chromosome inactivation can be estimated from the time of appearance of sex chromatin or late replication, or inferred from the appearance of heterozygotes for X-linked genes or of experimental chimaeras. The estimated time varies with species, and in the mouse and rabbit is near the time of increase in RNA synthesis.
4. Whereas in eutherian mammals either the maternally or the paternally derived X may be inactivated in different cell lines, in marsupials the paternal X is always the inactive one.
5. During development various factors act to distort the patterns produced by random X-inactivation. These factors include cell selection, transfer of gene product, and migration and mingling of cells.
6. There is no clear evidence that X-chromosome inactivation is not complete.
7. In female germ cells both X-chromosomes appear to be active. In male ones both X and Y appear inactive during most of spermatogenesis, although probably in early stages all X chromosomes present are active.
8. The active and inactive X-chromosomes may be differentiated by presence or absence of some non-histone protein or other polyanionic substance.
9. If the genes concerned in synthesis or attachment of this substance are on the X-chromosome then the differentiation will be self-maintaining.
10. The initiation of the differentiation requires either the attachment of different X-chromosomes to different sites, or some interaction of X-linked and autosomal genes, concerned in inducing or repressing activity. Some possible models are discussed.
586 citations
TL;DR: It is concluded that the deleterious effects of aneuploidy are mostly the consequence of the additive effects of genes that are slightly sensitive to abnormal dosage.
Abstract: By combining elements of two Y-autosome translocations with displaced autosomal breakpoints, it is possible to produce zygotes heterozygous for a deficiency for the region between the breakpoints, and also, as a complementary product, zygotes carrying a duplication for precisely the same region. A set of Y-autosome translocations with appropriately positioned breakpoints, therefore, can in principle be used to generate a non-overlapping set of deficiencies and duplications for the entire autosomal complement.-Using this method, we have succeeded in examining segmental aneuploids for 85% of chromosomes 2 and 3 in order to assess the effects of aneuploidy and to determine the number and location of dosage-sensitive loci in the Drosophila genome (Figure 5). Combining our data with previously reported results on the synthesis of Drosophila aneuploids (see Lindsley and Grell 1968), the following generalities emerge.-1. The X chromosome contains no triplo-lethal loci, few or no haplo-lethal loci, at least seven Minute loci, one hyperploid-sensitive locus, and one locus that is both triplo-abnormal and haplo-abnormal. 2. Chromosome 2 contains no triplo-lethal loci, few or no haplo-lethal loci, at least 17 Minute loci, and at least four other haplo-abnormal loci. 3. Chromosome 3 contains one triplo-lethal locus that is also haplo-lethal, few or no other haplo-lethal loci, at least 16 Minute loci, and at least six other haplo-abnormal loci. 4. Chromosome 4 contains no triplo-lethal loci, no haplo-lethal loci, one Minute locus, and no other haplo-abnormal loci.-Thus, the Drosophila genome contains 57 loci, aneuploidy for which leads to a recognizable effect on the organism: one of these is triplo-lethal and haplo-lethal, one is triplo-abnormal and haplo-abnormal, one is hyperploid-sensitive, ten are haplo-abnormal, 41 are Minutes, and three are either haplo-lethals or Minutes. Because of the paucity of aneuploid-lethal loci, it may be concluded that the deleterious effects of aneuploidy are mostly the consequence of the additive effects of genes that are slightly sensitive to abnormal dosage. Moreover, except for the single triplo-lethal locus, the effects of hyperploidy are much less pronounced than those of the corresponding hypoploidy.
584 citations
TL;DR: X-chromosome inactivation during spermatogenesis is proposed as the ideal system for studies of genetic control at the chromosomal level.
Abstract: Inactivation of the single X chromosome in the primary spermatocytes of species with heterogametic males is postulated as a basic control mechanism on the chromosomal level that is required for normal spermatogenesis. This view is supported by (a) cytological observations of X-chromosome allocycly in the primary spermatocytes of all male-heterogametic organisms that were adequately examined, (b) autoradiographic evidence of early cessation of transcription by the X chromosome in the mouse and three species of grasshopper, and (c) the male sterility of animals with certain X-chromosome rearrangements that cannot be attributed to misfunction of specific genes. X-chromosome inactivation during spermatogenesis is proposed as the ideal system for studies of genetic control at the chromosomal level.
479 citations
TL;DR: It is postulated that a chromomere is one cistron within which much of the DNA is regulatory in function.
Abstract: An average size chromomere of the polytene X chromosome of Drosophila melanogaster contains enough DNA in each haploid equivalent strand to code for 30 genes, each 1,000 nucleotides long. We have attempted to learn about the organization of chromosomes by asking how many functional units can be localized within a chromomere. This was done by 1) recovery of mutants representative of every cistron in the 3A2-3C2 region; 2) the characterization of the function of each mutant type and grouping by complementation tests; 3) the determination of the genetic and cytological position of each cistron by recombination and deletion mapping. The data clearly show one functional group per chromomere. It is postulated that a chromomere is one cistron within which much of the DNA is regulatory in function.
343 citations
TL;DR: Limited recombination data suggest that these mutants do not alter coincidence, and thus, following the arguments of Sandler et al. (1968), are defective in exchange rather than a precondiiton for exchange.
Abstract: A total of 209 ethyl methanesulfonate-treated X chromosomes were screened for meiotic mutants that either (1) increased sex or fourth chromosome nondisjunction at either meiotic division in males; (2) allowed recombination in such males; (3) increased nondisjunction of the X chromosome at either meiotic division in females; or (4) caused such females, when mated to males heterozygous for Segregation-Distorter ( SD ) and a sensitive homolog to alter the strength of meiotic drive in males.—Twenty male-specific meiotic mutants were found. Though the rates of nondisjunction differed, all twenty mutants were qualitatively similar in that (1) they alter the disjunction of the X chromosome from the Y chromosome; (2) among the recovered sex-chromosome exceptional progeny, there is a large excess of those derived from nullo- XY as compared to XY gametes; (3) there is a negative correlation between the frequency of sex-chromosome exceptional progeny and the frequency of males among the regular progeny. In their effects on meiosis these mutants are similar to In(1)sc 4L sc 8R , which is deleted for the basal heterochromatin. These mutants, however, have normal phenotypes and viabilities when examined as X/0 males, and furthermore, a mapping of two of the mutants places them in the euchromatin of the X chromosome. It is suggested that these mutants are in genes whose products are involved in insuring the proper functioning of the basal pairing sites which are deleted in In(1)sc 4L sc 8R , and in addition that there is a close connection, perhaps causal, between the disruption of normal X-Y pairing (and, therefore, disjunction) and the occurrence of meiotic drive in the male.—Eleven mutants were found which increased nondisjunction in females. These mutants were characterized as to (1) the division at which they acted; (2) their effect on recombination; (3) their dominance; (4) their effects on disjunction of all four chromosome pairs. Five female mutants caused a nonuniform decrease in recombination, being most pronounced in distal regions, and an increase in first division nondisjunction of all chromosome pairs. Their behavior is consistent with the hypothesis that these mutants are defective in a process which is a precondition for exchange. Two female mutants were allelic and caused a uniform reduction in recombination for all intervals (though to different extents for the two alleles) and an increase in first-division nondisjunction of all chromosomes. Limited recombination data suggest that these mutants do not alter coincidence, and thus, following the arguments of Sandler et al . (1968), are defective in exchange rather than a precondiiton for exchange. A single female mutant behaves in a manner that is consistent with it being a defect in a gene whose functioning is essential for distributive pairing. Three of the female meiotic mutants cause abnormal chromosome behavior at a number of times in meiosis. Thus, nondisjunction at both meiotic divisions is increased, recombinant chromosomes nondisjoin, and there is a polarized alteration in recombination.—The striking differences between the types of control of meiosis in the two sexes is discussed and attention is drawn to the possible similarities between (1) the disjunction functions of exchange and the process specified by the chromosome-specific male mutants; and (2) the prevention of functional aneuploid gamete formation by distributive disjunction and meiotic drive.
310 citations
TL;DR: It is concluded that founder events, inbreeding and geographic isolation play a major role in the development of reproductive isolate and that major adaptive incorporation of new alleles at a large number of structural loci is not necessary for the origin of reproductive isolation.
Abstract: F1 males obtained from the cross of D. pseudoobscura females from Bogota (Colombia) x males of this species from mainland, i.e. populations from various locations in the United States and from Guatemala, are sterile. This sterility is due to genes located on the X chromosome and the autosomes; the Y chromosome is not involved. The percentage of sterile males in backcrosses can be explained by assuming an interaction between two loci on the Bogota X chromosome and probably two loci, one each on two of the mainland autosomes. The role of founder events, inbreeding and geographic isolation in the development of reproductive isolation and the magnitude of gene differences responsible for the origin of reproductive isolation is discussed. It is concluded that founder events, inbreeding and geographic isolation play a major role in the development of reproductive isolation and that major adaptive incorporation of new alleles at a large number of structural loci is not necessary for the origin of reproductive isolation.
127 citations
TL;DR: The results indicate that the X-linked enzyme lacuts is expressed after fertilization but before the morula stage, and that inactivation of the X chromosome does not occur during oogenesis.
Abstract: The activity of hypoxanthine-guanine phosphoribosyltransferase in unfertilized mouse ova and in mouse embryos at the two-cell stage is proportional to the number of X chromosomes present during oogenesis. This indicates that the enzyme is X-linked in the mouse and that inactivation of the X chromosome does not occur during oogenesis. However, the genetic dosage effect of the X chromosomes is not present after the increase in hypoxanthine-guanine phosphoribosyltransferase activity in the late morula and the blastocyst stages. These results indicate that the X-linked enzyme lacuts is expressed sometimne after fertilization but before the morula stage.
114 citations
TL;DR: Tests on two such differing X chromosomes have indicated that the phenotypic modification results either from non-random inactivation of the two X chromosomes or from selection operating on the two cell populations differentiated by X-inactivation.
Abstract: X-linked modification of the heterozygous phenotypes of X-linked genes has been detected in the X chromosomes of several inbred strains of mice. The effect is similar to that of the alternative ‘states’ or alleles, of the X chromosome controlling element, Xce, identified in T(1; X)Ct X chromosomes. Tests on two such differing X chromosomes have indicated that the phenotypic modification results either from non-random inactivation of the two X chromosomes or from selection operating on the two cell populations differentiated by X-inactivation. The data provide evidence of non-random X chromosome activity in the somatic cells of the female mouse.
97 citations
TL;DR: Usinghuman somatic cell/mouse cell hybrids, no evidence for reactivation of the silent X chromosome in human somatic cells has been obtained.
Abstract: Using human somatic cell/mouse cell hybrids, no evidence for reactivation of the silent X chromosome in human somatic cells has been obtained.
90 citations
TL;DR: By use of human-mouse somatic cell hybrids, an autosomal gene linkage has been determined for the human loci controlling the phenotypes of lactate dehydrogenase-A and ester enzyme-A, and these structural loci were not linked to the lactate dehydration enzyme, peptidase-B, or to nine other enzyme phenotypes examined.
Abstract: By use of human-mouse somatic cell hybrids, an autosomal gene linkage has been determined for the human loci controlling the phenotypes of lactate dehydrogenase-A (EC 1.1.1.27) and esterase-A4 (EC 3.1.1.2). These structural loci were not linked to the lactate dehydrogenase-B, peptidase-B linkage, the X chromosome, the E17 chromosome, or to nine other enzyme phenotypes examined.
74 citations
TL;DR: The presence of the AB (hybrid) band demonstrates that both X-linked G6PD alleles are functional in the maturing human oocyte.
TL;DR: Evidence supports a cause-effect relationship between the extra X chromosome and spermatogenesis in Klinefelter's syndrome.
Abstract: The presence of an extra chromosome in the cells of patients with 47,XXY Klinefelter's syndrome and hypogonadism appears to be related phenomena. Testicular histopathology and function were compared in six patients with a 47,XXY karyotype and six patients with a 46,XY/47,XXY karyotype determined upon testicular cells. In addition, the frequency of clinical, histological, and hormonal abnormalities in these two groups of patients was compared following an extensive literature review. A greater degree of damage to the seminiferous tubules and germinal epithelium was found in the 47,XXY patients than in the 46,XY/47,XXY group. These results indicate that the normal 46,XY cells modify the damaging effect to the testis of the 47,XXY cells. This evidence supports a cause-effect relationship between the extra X chromosome and spermatogenesis in Klinefelter's syndrome.
TL;DR: A detailed cytogenetic study of male-viable and lethal deficiencies affecting the w-spl interval in Drosophila melanogaster has revealed the existence of genetic duplication such that the consequences of the loss of salivary chromosome band 3C3 are essentially compensated for by the presence of band3C5-6.
Abstract: A detailed cytogenetic study of male-viable and lethal deficiencies affecting the w-spl interval in Drosophila melanogaster has revealed the existence of genetic duplication such that, for example, the consequences of the loss of salivary chromosome band 3C3 are essentially compensated for by the presence of band 3C5-6, and vice versa. Although each of the duplicate elements possesses rst
+ and vt
+ activity, rst and vt phenotypes appear in males when 3C3 and part, but not all, of 3C5-6 are deleted. The degree of rst and vt expression can be correlated with the amount of material lost from 3C5-6. Deletions removing the entire 3C3-6 interval are male lethal. Despite the duplicate elements, at least one EMS-induced, presumptive point mutation expressing only rst is known; two others express both rst and vt. No loci other than rst and vt occur between W and spl. Band 3C2 appears to be associated with the w locus, which probably extends into the interband space between 3C1 and 3C2. The w locus is not involved in the rst-vt duplication in the 3C3-6 region. — The cytogenetic characteristics of the 3C region—a high coefficient of crossing over, frequent induced chromosome breakage, ectopic pairing, constriction, and an extended replication period—can be correlated with the fact that in 3C a relatively long stretch of DNA, nearly 2% of the entire X chromosome, is highly compacted into but few adjacent bands. These characteristics do not necessarily represent special properties of intercalary heterochromatin; they can be interpreted as reflecting the properties of any similarly organized euchromatic region.
TL;DR: Cytological examination of eight man-hamster clonal lines by the quinacrine fluorescent technique showed that human phosphoglycerate kinase was only present when the translocation chromosome carrying most of the long arm of the X chromosome was present.
Abstract: Man-mouse and man-Syrian hamster somatic hybrid cell lines were prepared by fusion of mouse A9 or hamster TG2 cells, which are deficient in hypoxanthine-guanine phosphoribosyl transferase, with cells of a diploid fibroblastic strain, KOP-1, derived from a woman heterozygous for an X-autosome translocation. 61 clones were derived in nonselective medium and 85 sublines of these were derived in selective media: 53 in hypoxanthine-aminopterine-thymidine and 32 in 8-azaguanine. All three human X-linked markers studied, i.e., hypoxanthineguanine phosphoribosyl transferase (EC 2.4.2.8), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), and phosphoglycerate kinase (EC 2.7.2.3), were present together, or absent together, in most of these clones and sublines. However, loss or retention of only phosphoglycerate kinase was occasionally observed, even in the absence of selective growth, while no evidence of separation of hypoxanthine-guanine phosphoribosyl transferase from glucose-6-phosphate dehydrogenase occurred. Cytological examination of eight man-hamster clonal lines by the quinacrine fluorescent technique showed that human phosphoglycerate kinase was only present when the translocation chromosome carrying most of the long arm of the X chromosome was present. The presence of human glucose-6-phosphate dehydrogenase and hypoxanthine-guanine phosphoribosyl transferase was not related to the presence or absence of this chromosome, but appeared to be correlated with the presence of the other translocation chromosome.
TL;DR: The interpretation offered here attributes msr to an interaction between sr sequence XS-I XL-II and the 0 condition, which is presumably identical to Novitski's "male sex ratio" (msr).
Abstract: In D. affinis "sex ratio" (sr), a form of meiotic drive characterized by the production of mostly or only female progeny by certain males, is associated with two different X chromosome sequences, XS-I XL-II and XS-II XL-IV. The behavior of the two sequences differed, depending on the Y chromosome constitution, being either YL or 0. Males with sequence XS-II XL-IV and YL produced progenies with nearly normal sex ratios; males with the same X chromosome sequence but in the absence of a Y chromosome in some cases gave progenies with nearly normal sex ratios but in other cases gave progenies which tended toward phenotypic sr. Males with sequence XS-I XL-II and YL gave progenies which were characteristically sr (0.97–0.98 females); in the absence of a Y chromosome males with this sequence produced progenies which were virtually all-male. This latter finding is presumably identical to Novitski's (1947) "male sex ratio" (msr). The interpretation offered here attributes msr to an interaction between sr sequence XS-I XL-II and the 0 condition. A general consideration of the available data on sr in D. affinis is presented.
TL;DR: It was found that in all 3 mosaic cultures the 45,X cells had a faster cell cycle than the second cell population and it is argued that heterochromatin has a retardative effect on cell division.
Abstract: Fibroblasts were grown from skin explants of 3 human females who are sex chromosome mosaics. The 3 cultures had the following chromosome complements: 45,X/46,XX, 45,X/46,XXqi and 45,X/47,XXX. Using thymidine labelling and Colcemid accumulation of metaphases it was found that in all 3 mosaic cultures the 45,X cells had a faster cell cycle than the second cell population. The difference in cell cycle duration was attributed to the longer G1 phase in the cells with 2 or 3 X chromosomes. The 2 populations of cells in the mosaic only differ in the number of heterochromatic X chromosomes and it is argued that heterochromatin has a retardative effect on cell division.
TL;DR: SEX-LINKED genes in mammals tend to produce a mosaic phenotype in the heterozygous female, which Lyon1 explained by assuming that, at an unidentified stage in the female embryo, one of the two X chromosomes in each cell becomes inactive in a random manner and remains so in all the descendants of this cell.
Abstract: SEX-LINKED genes in mammals tend to produce a mosaic phenotype in the heterozygous female, which Lyon1 explained by assuming that, at an unidentified stage in the female embryo, one of the two X chromosomes in each cell becomes inactive in a random manner and remains so in all the descendants of this cell. Russell and Bangham2 gave a similar explanation, but maintained that the inactivation did not involve the entire X chromosome and Gruneberg3 has argued that the inactivation is partial, but occurs in both the X chromosomes (see ref. 4).
TL;DR: Autoradiographic studies with 3H-thymidine show that the DNA at the centromeric regions starts and finishes its replication later than in the other parts of the chromosomes.
Abstract: Almost all the 30 chromosome pairs of cattle can be identified by their banding patterns made be visible by a Giemsa staining technique described previously. The banding pattern of the X chromosome shows striking similarities with the banding pattern of the human X chromosome. — The centromeric region of the acrocentric autosomes contains a highly condensed DNA. This DNA is removed by the Giemsa staining procedure as can be shown by interference microscopic studies. If the chromosomes are stained with quinacrine dihydrochloride these centromeric regions are only slightly fluorescent. — Autoradiographic studies with 3H-thymidine show that the DNA at the centromeric regions starts and finishes its replication later than in the other parts of the chromosomes.
TL;DR: Findings, taken with the incomplete data from two presumptive XXpi cases reported by others, indicate that the karotype 46, XXpi produces a clinical picture distinguishable from Turner's syndrome.
Abstract: SUMMARY
Cytogeetical and clinical findings in a 17 year-old female with te karyotype 46, XXpi are presented. The patient was 159 cm tall and had never menstruated. The gonads were not palpable and secondary sex characteristics were poorly developed. She had no somatic sgns of Turner's syndrome apart from a renal anomaly. The abnormal X chromosome could be identified as an Xpi by its characteristic fluorescence patterns and Giemsa staining properties after the ASG procedure. Autoradiography showed it to be the latest-labelling chromosome in nearly all cells. Sex chromatin bodies were normal in number and decreased in size (79% of normal). These findings, taken with the incomplete data from two presumptive XXpi cases reported by others, indicate that the karotype 46, XXpi produces a clinical picture distinguishable from Turner's syndrome.
The proposita and her father were Xg(a+), and her mother Xg(a−), indicating paternal derivation of the normal X chromosome. Hence the Xpi appears to be of maternal origin. Other interpretations are possible.
The findings lend added support to the hupothesis that genes controlling gonodal development are carried in both Xp and Xq, whereas those affecting stature are in Xp but probably not in Xq.
It is proposed that at isochromosome formation Xqi is far more likely to be produced than Xpi. This may be because breakage preferentially occcurs at the short-arm end of the centromere region or in the short arm itself, as indicated by the existence of presumptive dicentric Xqi chromosomes.
TL;DR: The use of clones derived from a female mule1 typed for Gd and at the same passage labelled with 3H-TdR and subsequently autoradiographed should provide final proof of this relationship between late DNA replication and X chromosome inactivation.
Abstract: THE relationship between late DNA replication and X chromosome inactivation is supported by strong circumstantial evidence1–3. The use of clones derived from a female mule1 typed for Gd and at the same passage labelled with 3H-TdR and subsequently autoradiographed should provide final proof of this relationship.
TL;DR: The somatic cells of female mammals are functional mosaics with the X chromosome of maternal origin active in some cells and the paternal X active in the remainder, according to the Lyon hypothesis.
Abstract: ACCORDING to the Lyon hypothesis the somatic cells of female mammals are functional mosaics with the X chromosome of maternal origin active in some cells and the paternal X active in the remainder1. Lyon also postulated that inactivation of X chromosomes occurs in early embryonic development and implied that, once inactivation occurs in any one cell, all descendants of that cell carry the same inactive X chromosome.
TL;DR: This study was undertaken to determine whether genes at the X-linked loci for glucose-6-phosphate dehydrogenase and phosphoglycerate kinase are consistently expressed in the eis position in cloned cells as would be expected from a single parental contribution.
Abstract: THE Lyon hypothesis of X chromosome inactivation predicts that in mammalian females, somatic cells are mosaic with respect to whether the active X chromosome is of maternal or paternal origin and that this chromosomal mosaicism is heritable somatically1. Studies of cell clones derived from females who were heterozygous for genes at one of several X-linked loci2–6 have provided good evidence for such mosaicism. Proof that only one of the two X chromosomes, however, is active in any given cell rests on the demonstration that the cell or its clone expresses all of the X-linked genes from one parent and none from the other parent. For this purpose it is useful to examine cloned cells from female subjects for genetic markers representing allelic genes at two or more of the parental loci. This study was undertaken to determine whether genes at the X-linked loci for glucose-6-phosphate dehydrogenase (G6PD) and phosphoglycerate kinase (PGK) are consistently expressed in the eis position in cloned cells as would be expected from a single parental contribution.
TL;DR: This study has obtained further and more rigorous proof that late replication of the X chromosome corresponds to genetic inactivation at the G-6-PD locus, and obtained data bearing on the problem of the postulated randomness of inactivation.
Abstract: IN the female mule (Equus caballus × E. asinus), the horse (maternal) and the donkey (paternal) X chromosomes are morphologically distinguishable1,2, and the X-linked enzyme, glucose-6-phosphate dehydrogenase (G-6-PD), is present as a combination of the two electrophoretically distinct parental forms3,4. Female mule cells therefore may serve as an experimental model for the simultaneous study of both cytological and biochemical aspects of dosage compensation for X-linked loci in mammals (Lyon hypothesis5). We have demonstrated a very close correlation between late replication of either one or the other of the parental X chromosomes, and relative activity of the complementary form of G-6-PD6. In this study we have obtained further and more rigorous proof that late replication of the X chromosome corresponds to genetic inactivation at the G-6-PD locus. We have also obtained data bearing on the problem of the postulated randomness of inactivation.
TL;DR: A study on migratory melanocytes, which are of a different origin and which start forming pigment later, and which probably occurs much later than had formerly been thought on retinal melanocytes of the mouse.
Abstract: THE mosaic phenotype associated with many sex-linked genes in heterozygous females in mammals is generally believed to result from the random inactivation of one X chromosome in each cell during development1,2. Inactivation is thought to occur quite early in embryonic life and more or less at the same time in all cells of the embryo3. Having earlier4 shown that in the retinal melanocytes of the mouse it probably occurs much later than had formerly been thought, we have now carried out a similar study on migratory melanocytes, which are of a different origin and which start forming pigment later.
TL;DR: It was concluded that the difference between the selected lines was due either to non-random inactivation or to somatic cell selection, and it was not possible to distinguish between these two mechanisms.
Abstract: The sex-linked gene, brindled , in the mouse produces a coat-colour variegation in heterozygous females. There is much individual variation in the relative areas of mutant and wild-type colour, but it was not known if any of this variation was genetic. The main object, when the experiments were started, was to test the simple expectation of the Lyon hypothesis, that if X -inactivation is random the variegation should not be modifiable by selection. On the assumption that the variegation is due to X -chromosome inactivation, modification by selection would show that the inactivation process, or some property of the derived cell populations, is under genetic control. Heterozygous females were accordingly selected for the area of coat showing the mutant colour. Selection based on individual phenotypes was ineffective, but four cycles of reciprocal recurrent selection based on progeny-means produced a ‘High’ line with 64% mutant area and a ‘Low’ line with 30% mutant area, from a base population with 53% mutant area. Autosomal modifiers were not responsible for the response; the difference between the selected lines was entirely due to properties of the X chromosomes carrying the brindled gene. The changed properties of the X chromosomes were not restricted to the locus of brindled , but extended at least as far as the locus of tabby . The chromosomes carrying the wild-type allele of brindled were not altered by the selection, but normal X chromosomes from other strains affected the degree of variegation. It was concluded that the difference between the selected lines was due either to non-random inactivation or to somatic cell selection. It was not possible to distinguish between these two mechanisms. The results obtained in these experiments with a structurally normal X chromosome were in all essentials similar to those obtained by Cattanach with his X -autosome translocation.
TL;DR: Electron microscopy revealed a short synaptonemal complex in mouse meiotic cells and supported the hypothesis that the X and Y chromosomes associate only by connexion between the chromosome ends furthest from the centromeres.
Abstract: ACCORDING to the hypothesis of Crew and Koller1 and Koller and Darlington2, there are homologous segments in the X and Y chromosomes of the mouse and other mammals. The homologous regions in the mouse were believed to be localized in the extremely short arms proximal to the kinetochores. The end-to-end association at meiosis was thought to be the result of the formation of a chiasma between these homologous regions3. Electron microscopy revealed a short synaptonemal complex in mouse meiotic cells4. However, partial sex linkage has never been demonstrated in the mouse5 and other authors6–10 believe that the X and Y chromosomes associate only by connexion between the chromosome ends furthest from the centromeres.
TL;DR: Observations support the conclusion that the entire human X chromosome can be involved in X inactivation.
Abstract: The fibroblasts derived from the skin of a woman heterozygous for an X-linked deficiency of phosphoglycerate kinase represented a mosaic. Two of 22 clones with normal glucose-6-phosphate dehydrogenase activity and hypoxanthine(guanine) phosphoribosyltransferase activity had no phosphoglycerate kinase activity detected by electrophoresis. Because the loci for glucose-6-phosphate dehydrogeniase and hypoxanthine(guanine)phosphoribosyltransferase are already known to undergo inactivation and to be on the short arm of the X chromosome and the locus for phosphoglycerate kinase is on the long arm, these observations support the conclusion that the entire human X chromosome can be involved in X inactivation.
Journal Article•
TL;DR: The components of the sequence, conventionally designated by Roman numerals but also possessing physiologic appellations, have been defined by combining biochemical analysis with the physiologic study of mutant phenotypes and members of their families.
Abstract: The coagulation of blood may be regarded as the final step in a sequence of physiologico-chemical reactions, each prior step of which triggers a subsequent one [ 1, 21]. The components of the sequence, conventionally designated by Roman numerals but also possessing physiologic appellations, have been defined by combining biochemical analysis with the physiologic study of mutant phenotypes and members of their families. Mutant phenotypes have been described in humans for 10 of the 13 components or "factors" of the sequence (Factors I, II, V, VII, VIII, IX, X, XI, XII, and XIII) and in dogs for at least three (Factors VII, VIII, IX). As expected, most of the mutated loci reside on autosomal chromosomes (I, II, V, VII, X, XI, XII, XIII), but two are X linked in both species (VIII, IX). The mutations are rare, and the two most commonly encountered abnormal phenotypes are the X-linked hemophilias A (Factor VIII, AHF deficiency) and B (Factor IX, Christmas-factor deficiency). The frequency in humans of the abnormal gene producing hemophilia A has been estimated to be 1-1.7 X 10-4 and for hemophilia B, 2-3 X 10-5 3 ]. The hemophilia-A locus is known to be linked to the colorblindness and glucose-6-phosphate dehydrogenase loci, but the hemophilia-B locus has not yet been linked to any other locus on the X chromosome [4]. The abnormal phenotypes are usually ascertained through the existence of a hemorrhagic diathesis, and confirmation is by use of an in vitro bioassay. Identification of the abnormal phenotypes has depended upon demonstration of retarded coagulation values under test-tube conditions. Specific identification of an abnormality has depended upon matching the abnormal plasma against a battery of previously defined abnormal plasmas in a type of complementation test. When the unknown abnormal plasma sample fails to improve coagulation of one member of the abnormal battery but is able to improve the retarded coagulation of all others,
TL;DR: Evidence was obtained that mitotic recombination between ring and rod chromosomes results, in a majority of cases, in XO spots, bearing the rod-X only, which would indicate that somatic pairing of homologues is not accurate in X chromosome inversion heterozygotes and consequently, that recombination yields aneuploid cells.
Abstract: Mitotic recombination has been induced with X-rays in Drosophila melanogaster larvae and assayed later as twin mosaic spots on the adult tergites. With the use of the In(1)sc4Lsc8R chromosome which lacks the nucleolar organizer and is marked with yellow (y) indirect evidence was obtained that mitotic recombination between ring and rod chromosomes results, in a majority of cases, in XO spots, bearing the rod-X only. This was concluded from the relative scarcity and small sizes of y NO- spots (uncovering the sc4sc8 chromosome), compared to control sisters bearing an extra Y chromosome with its NO locus. Thus, dicentric chromatid bridges formed by mitotic recombination between the ring and rod chromosomes are probably eliminated at the next division.