Showing papers on "Chromosome 21 published in 1977"

Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants.

Abstract: A number of individuals with aberrant Y chromosomes have been tested for the presence of Y-chromosome-specific reiterated DNA. These studies locate Y-chromosome-specific reiterated sequences on the long arm of the Y chromosome. Correlation with phenotype and other known Y chromosome markers establish that the Y-chromosome-specific reiterated DNA discussed here has no evident role in male determination.

The status of the gene map of the human chromosomes

Abstract: In man, the specific chromosome that carries each of about 210 gene loci is known. These loci include at least one assigned to each chromosome (including the Y), about 110 assigned to specific autosomes, and about 100 to the X chromosome. For many loci, information on regional chromosomal localization is also available. The information comes mainly from studies in families and somatic cell hybrids, as well as an intgratsight of results from the two methods. Knowledge of the chromosome map gives insight into evolution, chromosomal organization in relation to genetic control mechanisms, and the pathogenesis of neoplasms and malformations. Furthermore, it is useful in prenatal or premorbid diagnosis of hereditary diseases.

Mapping of human chromosomal regions related to neoplasia: evidence from chromosomes 1 and 17.

Abstract: In clonal aberrations leading to an excess or partial excess of chromosome 1, trisomy for bands 1q25-1q32 was noted in the myeloid cells from all of 34 patients who had various disorders such as acute leukemia, polycythemia vera, and myelofibrosis. This was not the result of a particularly fragile site in that region of the chromosome because the break points in reciprocal translocations that involve it occurred almost exclusively in the short arm. Two consistent rearrangements that have been observed in chromosome 17 produced either duplication of the entire long arm or a translocation of the distal portion of the long arm to chromosome 15. The nonrandom chromosomal changes found in hematologic disorders can now be correlated with the gene loci on these chromosomes or chromosomal segments. Seventy-five genes related to various metabolic enzymes have been mapped; it may be significant that chromosomes carrying gene loci related to nucleic acid metabolism are more frequently involved in hematologic disorders (and other malignancies as well) than are gene loci related to intermediary or carbohydrate metabolism. Furthermore, the known virus-human chromosome associations are closely correlated with the chromosomes affected in hematologic disorders. If one of the effects of carcinogens (including viruses) is to activate genes that regulate host cell DNA synthesis, and if translocations or duplications of specific chromosomal segments produce the same effect, then either of these mechanisms might provide the affected cell with a proliferative advantage.

Assignment of the major histocompatibility complex to a region of the short arm of human chromosome 6

Abstract: Interspecific cell hybrids containing defined parts of human chromosome 6 were used for regional mapping of gene loci previously assigned to chromosome 6: the human leukocyte antigens (HLA) region, phosphoglucomutase-3 (PGM3; alpha-D-glucose-1,6-bisphosphate:alpha-D-glucose-1-phosphate phosphotransferase, EC 2751) and malic enzyme-1 [malic dehydrogenase(decarboxylating) (NADP+), L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC 11140] Human fibroblasts containing a balanced reciprocal translocation between the short arms of chromosome 1 and chromosome 6--designated t(1;6) (p3200;p2100)--were fused with an established line of Chinese hamster cells Hybrid clones with segregating human chromosomes were studied for the presence of the translocation chromosomes 1T and 6T and their normal homologues 1 and 6 Six clones that had retained 1T, three clones with 6T, and three clones with 6 and 6T as controls, were analyzed by a microabsorption test for expression of the allelic antigens HLA-A2 and HLA-A3, both of which were present on the human parental cells HLA-A2 segregated with the 1T translocation chromosome and HLA-A3 with the normal chromosome 6 Hybrid clones with 6T did not possess an HLA-A gene In contrast, human PGM3 and malic enzyme-1 expression segregated with the 6T translocation chromosome These results indicate the location of the major histocompatibility complex in region 6p2100 leads to 6pter of the short arm of chromosome 6 The genes for PGM2 and malic enzyme-1 map in region 6p2100 leads to 6qter The HLA:PGM3 genetic map distance is 15 centimorgans in males, as established by family studies This allows rather precise mapping of both loci because HLA is distal and PGM3 proximal to the translocation breakpoint in band 6p2100 The findings are consistent with earlier conclusions that HLA is proximal to 6p22 Quantitative correlation between the density of HLA antigens on the hybrid cell surface and the number of copies of the respective HLA gene-bearing chromosome suggests a gene dose effect for cell surface molecules, as it exists for intracellular gene products

Dosage effects for superoxide dismutase-1 in nucleated cells aneuploid for chromosome 21.

Abstract: Assays of the activity of chromosome 21 determined superoxide dismutase-1 (SOD-1) in lymphocytes and polymorphonuclear granulocytes have demonstrated 38% and 40% increases, respectively, in cells from individuals with trisomy 21. Similarly, SOD-1 activity in trisomic fibroblasts is increased by 81%, while cells monosomic for chromosome 21 have only 60% of normal activity. Taken together with the data on SOD-1 activities in trisomic erythrocytes and platelets, the present results firmly confirm the existence of a true dosage effect for this enzyme in cells aneuploid for chromosome 21. However, the results of assays of the activity of glutathione peroxidase in trisomic fibroblasts did not confirm the possibility previously reported of a chromosome 21 related dosage effect for this enzyme.

Gene mapping in Mus musculus by interspecific cell hybridization: assignment of the genes for tripeptidase-1 to chromosome 10, dipeptidase-2 to chromosome 18, acid phosphatase-1 to chromosome 12, and adenylate kinase-1 to chromosome 2.

Abstract: Chinese hamster X mouse somatic cell hybrids segregating mouse chromosomes were examined for their mouse chromosome content using trypsin-Giemsa (GTG) banding and Hoechst 33258 staining techniques. Si

Mapping the locus of the H-Y gene on the human Y chromosome.

Abstract: The H-Y locus is on the short arm of the human Y chromosome in most individuals but on the long arm in at least one of 17 individuals with structural abnormalities of the Y.

Preferential derivation of abnormal human G-group-like chromosomes from chromosome 15

Abstract: The marked binding of antibodies specific for 5-methylcytidine to the short arm of chromosome 15 distinguishes this chromosome from the other human acrocentrics. This method has been used to study over 60 individuals including 12 who did not have Down's syndrome, but who did have an extra G-group sized acrocentric chromosome. In six cases the extra chromosome did not show intensive binding of anti-5-methylcytidine. In the other six cases, the extra chromosome contained a 5-methylcytidine rich band at each end indicating that both ends were derived from chromosome 15 and contained centromeric heterochromatin normally present on the short arm of chromosome 15. The duplication of short arm material in the abnormal chromosomes was confirmed in all cases by quinacrine staining, nucleolar organizer (Ag-AS) staining or C-banding. In three cases, the abnormal chromosome appeared to arise from two different chromosomes 15. Several possible mechanisms for the production of the abnormal chromosome are discussed. The individuals with this abnormal chromosome all showed some degree of mental retardation, but few common physical findings.

Inverted tandem (“mirror”) duplications in human chromosomes: Inv dup 8p, 4q, 22q

Abstract: We have studied 4 patients with inverted tandem duplications of parts of chromosomes, a hitherto rarely identified form of a structural rearrangement involving a single chromosome in man. In patients 1 and 2, the duplication involved parts of the short arm of chromosome 8 (regions 8p12 leads to 8p23 and 8p21 leads to 8p23, respectively). Both patients manifested certain characteristics of the mosaic trisomy 8 syndrome. Elevated levels of glutathione reductase (GSR) in their erythrocytes supported the interpretation of a partial duplication of chromosome 8 and indicated a regional localization for the GSR gene locus. In Partient 3, the distal half of the long arm of chromosome 4 was duplicated (region 4q23 leads to 4q35). Clinical evidence supported this interpretation, as Patient 3 resembled phenotypically the 13 reported cases with duplication of the distal 4q. The cytogenetic findings in Patient 4 suggested a possibly inverted duplication of 22q. The clinical correlation was less convincing due to the lack of a well-defined phenotype for trisomy 22. These chromosome aberrations had occurred de novo in all 4 cases. Although they involved different chromosomal regions, they might well have arisen by the same mechanism. Possible modes of origin that are discussed in detail include unequal exchange between homologous chromosomes, between chromatids of 1 chromosome or between strands of 1 DNA duplex.

Chromosome loss is responsible for segregation at the HPRT locus in Chinese hamster cell hybrids.

Abstract: The phenomenon of segregation of gene expression has been examined in intraspecific somatic cell hybrids. Specifically, segregation at the hypoxanthine guanine phosphoribosyltransferase (HPRT)locus has been studied in hybrids of Chinese hamster cell lines. The role of chromosome segregation, or other chromosomal events has been assessed by detailed comparison of karyotypes in the 6-thioguanine resistant segregants with those of the parental hybrid lines. The results clearly demonstrate that loss of an entire X chromosome is the primary event responsible for segregation at the HPRTlocus, while deletion of a portion of the short arm of an X chromosome was also a frequent event. The results provide the first direct evidence for the assignment of the HPRTlocus to the X chromosome in Chinese hamster, and in fact allow mapping of this locus to the distal region of the short arm. Analysis of chromosome number distributions in the hybrids and segregants suggests that in selecting chromosomal segregants one may also select for hybrid lines with reduced chromosome stability.

Parental origin of the extra chromosome in Down's syndrome.

Abstract: Chromosome 21 fluorescent heteromorphisms were studied in 42 patients with Down's syndrome, their parents and their siblings. Included in this number are two instances of an aunt and niece affected with trisomy 21, and one of affected siblings. One case has a de novo 21/21 translocation. Blood group, red cell and serum protein markers were also studied for linkage, gene exclusions, associations, and paternity testing. Thirty-one of the trisomy 21 cases were informative for parental origin of the extra chromosome and for stage of meiosis. The non-disjunctional event was of maternal origin in 24; 23 occurred in meiosis I, 1 in meiosis II. Seven were of paternal origin; 5 in meiosis I, and 2 in meiosis II. The translocation case was of paternal origin. A literature search revealed a total of 98 cases informative for the parent of origin of the extra chromosome, of >347 families tested. In addition, 3 de novo translocation cases, of 7 tested, were informative. The data suggest that most cases result from an error in the first meiotic division in the mother, but that a significant proportion are paternal in origin.

The repair of X-ray induced chromosomal damage in trisomy 2-and normal diploid lymphocytes.

Abstract: The frequency of chromosomal aberrations produced by X-rays is greater in lymphocytes cultured from trisomy 21 patients (Down's syndrome) than from normal diploid donors. This increase, which can be detected by a micronucleus assay for chromosomal damage, was postulated by us to result from a defect in the rejoining system which repairs chromosomal breaks. The postulated defect would result in a longer rejoining time, therapy permitting more movement of broken ends and thus enhancing the frequency of exchanges. To test this possibility, the time required for the rejoining (repair) of chromosome breaks was measured in lymphocytes from five Down's syndrome (four trisomy 21 and one D/G translocation partial trisomy 21) donors, from a monosomy 21 donor, and from five diploid donors. The rejoining time was reduced in the Down's syndrome lymphocytes in comparison to the normal diploid and monosomy 21 lymphocytes. Thus the repair of chromosome breaks, far from being defective as evidenced by a longer rejoining time in Down's syndrome cells, occurred more rapidly than in normal cells. A mechanism is proposed by which reduced rejoining times would increase aberration frequencies as a consequence of competition between a (hypothetical) error-free repair system and the error-prone repair system that generates chromosomal aberrations. We suggest that the alteration in the rejoining of chromosomal aberrations may underlie the increased susceptibility of people with Down's syndrome to leukemia.

Partial trisomy of the long arm of human chromosome 1 as demonstrated by in situ hybridization with 5S ribosomal RNA

Abstract: In a newborn boy with multiple malformations, a tandem duplication was detected at the distal end of the long arm of one human chromosome 1. The Giemsa bands, 1q31 to 1q43--44, were repeated serially. Since 5S rRNA genes are located at 1q42--43, in situ hybridization of 125I 5S rRNA with fixed chromosome preparations was used to confirm the chromosomal duplication. The infant exhibited numerous developmental and clinical abnormalities as might be expected with an abnormality of chromosome structure relating to a ribosome component.

15/15 translocation in Prader-Willi syndrome.

Abstract: Two further cases (one previously published as D/D translocation) of 15/15 translocation in Prader-Willi syndrome are reported, which brings the total cases of this specific chromosomal anomaly in connection with this specific syndrome up to three or possibly four. It is suggested that Prader-Willi syndrome might be caused by loss of short arm material of chromosome 15.

Assignment of the DIA1 locus to chromosome 22.

Abstract: SUMMARY Human/rodent hybrid cell cultures were examined for the presence of 1 and other marker enzymes. Many of these hybrids were also analysed for human chromosomes. Complete concordance was found only with chromosome 22.

Effect of human interferon preparations on lymphoblastogenesis in Down's syndrome.

Abstract: The best characterised properties of human interferon, its antiviral (AV) and cell multiplication inhibitory (CMI) activities, are controlled, in an unexplained manner, by genes on chromosomes 21 (refs 1-4; 14-16). Human and animal interferons have various immunosuppressive effects, among them the inhibition in vitro of DNA synthesis in activated lymphocytes. Using mitogen- and antigen-stimulated lymphocytes from normal subjects (disomic 21) and others with Down's syndrome (trisomic 21), we have found that DNA synthesis is inhibited to a greater degree in the latter by both fibroblastoid and leukocyte interferons. We suggest that this property is also regulated by genes on chromosome 21.

Ring chromosome 4.

Abstract: A mentally and physically retarded boy with a 46,XY,ring (4) (p16q35) chromosome complement is described Chromosome banding showed that the amount of chromosome material deleted from the ring chromosome 4 was minimal, apparently no more than the telomeres Chromosomal aberrations appear to be restricted to the production of double-sized dicentric rings, and aneuploidy The mosiacism resulting from the behavioural peculiarities of ring chromosomes is described as dynamic mosaicism It is suggested that the clinical features associated with this ring chromosome are more likely to be the result of the effects of a diploid/monosomy 4/polysomy 4 mosaicism than to the deficiency of the telomeric regions of the chromosome

The Role of Human Chromosome 21 in Sensitivity to Interferons

Abstract: Summary Cultures of human fibroblasts trisomic for chromosome 21 were more sensitive to human leukocyte and human fibroblast interferons than were human diploid fibroblasts; these in turn were more sensitive than fibroblasts monosomic for chromosome 21. The sensitivities of these cells to human interferons correlated with the amounts of interferons which they bound. These data indicate that some gene on chromosome 21 codes for an interferon-receptor component. Also, interferon from a heterologous species (mouse) was respectively much more and somewhat more active in trisomic and disomic cells than in monosomic cells. These data suggest that heterologous and homologous interferons may share common receptor component(s) coded by chromosome 21. Alternatively, human chromosome 21 may carry genetic information for some factor(s) responsible for increasing the exposure of certain surface receptors which are themselves coded by other chromosomes.

Association of chromosome loss with centromere-adjacent mitotic recombination in a yeast disomic haploid.

Abstract: Experiments designed to characterize the association between disomic chromosome loss and centromere-adjacent mitotic recombination were performed. Mitotic gene convertants were selected at two heteroallelic sites on the left arm of disomic chromosome III and tested for coincident chromosome loss. The principal results are: (1) Disomic chromosome loss is markedly enhanced (nearly 40-fold) over basal levels among mitotic gene convertants selected to arise close to the centromere; no such enhancement is observed among convertants selected to arise relatively far from the centromere. (2) Chromosome loss is primarily associated with proximal allele conversion at the centromere-adjacent site, and many of these convertants are reciprocally recombined in the adjacent proximal interval. (3) Partial aneuploid exceptions provisionally identified as carrying left arm telocentrics have been found. A testable model is proposed suggesting that centromere involvement in genetic recombination may precipitate segregational disfunction leading to mitotic chromosome loss.

Familial translocation with partial trisomy of 13 and 22: evidence that specific regions of chromosomes 13 and 22 are responsible for the phenotype of each trisomy.

Abstract: A newborn infant with clinical and pathological findings typical trisomy 13 and 22 syndromes had an extra chromosome which was a derivative chromosome from maternal balanced translocation affecting Nos. 13 and 22; 47,XY,+der(22),t(13:22)(q22:q12)Mat. The presence of extra specific euchromatic regions of No. 13(13q22 and/or 13q34) and No. 22 (22q11) seem to be responsible for the trisomy 13 and 22 syndromes.

Gene dosage for isocitrate dehydrogenase in mouse embryos trisomic for chromosome 1

Abstract: IT is generally assumed that changes in chromosome number are reflected in gene dosage effects for loci located in the extra or missing chromosomes. Although such effects have been well substantiated in Drosophila1 data for mammalian aneuploidy are scarce. Quantitative gene dosage effects have been demonstrated for several X-linked enzymes in oocytes of mice with X-chromosome aneuploidy2,3 and for malic enzyme in mice with partial trisomy of chromosome 7 (ref. 4). In man, similar effects for superoxide dismutase-1 (W. W. Feaster, L. W. Kwok and C.J.E., unpublished and ref. 5), adenine phosphoribosyltransferase6, purine nucleoside phosphorylase7 and erythrocyte acid phosphatase8 have been observed in cells aneuploid for chromosomes 21, 16, 14 and 2, respectively. Aneuploidy for chromosome 21 also affects responsiveness to interferon9, and XYY cells have been claimed to have increased amounts of H–Y surface antigen10. Since the detection of more than 30 metacentric (Robertsonian translocation) chromosomes in wild and laboratory strains11,12 and the development of a mating scheme which utilises such translocations for the production of aneuploid embryos in relatively high frequencies13,14, the mouse has become particularly useful for gene dosage studies. We have used this system to demonstrate the dosage effect for supernatant isocitrate dehydrogenase (Id-1) which results from trisomy for chromosome 1.

Partial trisomy 20 (20q13) and partial trisomy 21 (21pter leads to 21q21.3).

Abstract: A patient with a double partial trisomy 20 and 21 with mild mental retardation and multiple congenital anomalies is presented. Despite trisomy for a substantial portion of chromosome 21, the patient showed only minor stigmata compatible with Down syndrome.

Deletion of the short arm of chromosome No. 10.

Abstract: . A new case of deletion of the short arm of chromosome no. 10 is reported. The individualization of a new autosomal syndrome associated with a 10p- aberration is discussed.

A fluorescence polymorphism associated with Down's syndrome?

Abstract: Fluorescence polymorphism frequencies have been determined for a group of 85 Down's syndrome cases and 164 controls. For one class of polymorphism, that of positive satellites of chromosome 21, the frequency in the Down's cases was significantly higher than in the controls; the distribution of positive satellites in the mongols indicates that in the majority the extra chromosome arose by first meiotic non-disjunction. The possibility that positive satellites on chromosome 21 could be a causative factor in Down's syndrome is discussed, and the implications of this possibility on the assessment of the risk of producing a Down's child are examined.

Elevated expression of T-antigen in simian papovavirus 40-infected skin fibroblasts from individuals with cytogenetic defects.

Abstract: A number of cytogenetic conditions were examined for expression of simian papovavirus 40 T-antigen in vitro . Skin fibroblasts from patients with Turner's syndrome and trisomy 18 syndrome and most cell lines from Klinefelter's syndrome, trisomy 13 syndrome, chromosomal translocations, chromosome 21 deletions, and single cases of 18q-and 4p- exhibited elevated T-antigen expression, compared to a clinically and cytogenetically normal control population. Thus, T-antigen expression was generally elevated in cells with increased, decreased, or rearranged genetic material involving many different chromosomes. Variation in T-antigen expression among cell lines may reflect two factors. Individual cell line factors may account for differences within homogeneous clinical groups, whereas population factors appear to account for differences between the various clinical groups and the control population. The observation of elevated T-antigen expression in diverse cytogenetic conditions suggests that this phenomenon may be a manifestation of chromosomal aberration unrelated to cancer susceptibility.

13q- syndrome. Family study.

Abstract: A patient is described who had a deletion involving the long arm of chromosome number 13. The mother and 4 of 7 living sibs showed a balanced translocation from the long arm of a number 13 chromosome to the long arm of a number 3 chromosome. We stress the importance of investigating the families of children with chromosomal defects.

Intrachromosomal gene mapping in man: The gene for tryptophanyl-tRNA synthetase maps in region q21→qter of chromosome 14

Abstract: A gene for tryptophanyl-tRNA synthetase (EC 6.1.1.2), the enzyme which attaches tryptophan to its tRNA, has previously been assigned to human chromosome 14 by analysis of man-mouse somatic cell hybrids. We report here a method for the electrophoretic separation of Chinese hamster and human tryptophanyl-tRNA synthetases and its application to a series of independently derived Chinese hamster-human hybrids in which part of the human chromosome 14 has been translocated to the human X chromosome. When this derivative der (X),t(X;14) (Xqter → Xp22::14q21 → 14qter) chromosome carrying the human gene for hypoxanthine-guanine phosphoribosyltransferase was selected for and against in cell hybrid lines by the appropriate selective conditions, the human tryptophanyl-tRNA synthetase activity was found to segregate concordantly. These results provide additional confirmation for the assignment of the tryptophanyl-tRNA synthetase gene to human chromosome 14 and define its intrachromosomal location in the region 14q21 → 14qter. Our findings indicate that the genes for tryptophanyl-tRNA synthetase and for ribosomal RNA are not closely linked on chromosome 14.

Down's syndrome and deletion of short arms of a G chromosome.

Abstract: A woman in a family in which a G group chromosome (No. 21) with deleted short arms (21p-) is present has passed this chromosome to an intellectually deficient son, a normal son, and a daughter with Down's syndrome. Another daughter is chromosomally and phenotypically normal. As in other reports that focus on a concurrence of Gp- chromosomes and Down's anomaly, the possibility is considered that this chromosomal variant may predispose to developmental abnormalities or to non-disjunction, or both.