Showing papers on "Chromosome published in 1987"

Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development.

Abstract: This paper shows stage- and tissue-specific global demethylation and remethylation occurring during embryonic development. The egg genome is strikingly undermethylated and the sperm genome relatively methylated. Following a loss of genomic methylation during preimplantation development, embryonic and extraembryonic lineages are progressively and independently methylated to different final extents. Methylation continues postgastrulation and hence could be a mechanism initiating, or confirming, differential programming in the definitive germ layers. It is proposed that much of the methylation observed in somatic tissues acts to stabilize and reinforce prior events that regulate the activity of specific genes, chromosome domains or the X chromosome (in females). Fetal germ cell DNA is markedly undermethylated and we favour the idea that the germ lineage is set aside before the occurrence of extensive methylation of DNA in fetal precursor cells.

The gene for familial polyposis coli maps to the long arm of chromosome 5.

Abstract: The inherited genetic defect in adenomatous polyposis has been localized to a small region on the long arm of chromosome 5. Sixteen DNA marker loci were used to construct a linkage map of the chromosome. When five kindreds segregating a gene for adenomatous polyposis coli were characterized with a number of the markers, significant linkage was found between one marker and the disease gene. Linkage analysis determined the location of the defective gene within a primary genetic map of chromosome 5.

Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma.

Abstract: Loss of genes at specific chromosomal loci is a characteristic of retinoblastoma, Wilms' tumour, transitional cell carcinoma of the bladder, embryonal tumours and small cell carcinoma of the lung. The significance of nonrandom gene loss in these neoplasms is that gene loss on one chromosome may uncover null mutations at corresponding loci of the homologous chromosome. Loss of specific gene products from somatic cells may be critical in the origin or evolution of certain human tumours. Clues to identification of new loci of gene loss in common adult solid tumours may be found in literature that describes chromosomal abnormalities in rare heritable cancers. Karyotypes of tumours in two families with hereditary renal carcinoma showed translocations involving the short arm of chromosome 3 (refs 10 and 11). We have examined tumours from 18 patients with non-hereditary renal cell carcinomas and found loss of alleles at loci on the short arm of chromosome 3 in all eleven of the patients who could be evaluated.

Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung

Abstract: By a molecular genetic approach using polymorphic DNA markers that detect allelic deletion of specific chromosomal regions, we analyzed for possible loss of chromosomal heterozygosity in five different histological types of lung cancers obtained from 47 patients. In small-cell carcinomas, the incidence of allelic deletions at three different chromosomal loci was extremely high; loss of heterozygosity was detected on chromosomes 3p in 7 of 7 patients (100%), 13q in 10 of 11 patients (91%), and 17p in 5 of 5 patients (100%). The deletions at these loci in small-cell carcinomas were observed even in the tumors without any clinical evidence of metastasis. Furthermore, loss of heterozygosity on chromosomes 3p and 13q occurred prior to NMYC amplification and chromosome 11p deletion. Loss of heterozygosity on chromosome 3p was also detected with high frequency in adenocarcinomas [5 of 6 patients (83%)]. Heterozygosity of chromosomes 13q and 17p was lost in 10 of 31 patients (32%) and in 3 of 12 patients (25%), respectively, of lung cancers other than small-cell carcinomas. These results indicate that recessive genetic changes involving sequences on chromosomes 3p, 13q, and 17p may play important roles in the genesis of small-cell carcinoma, and those on chromosome 3p may play an important role in the genesis of adenocarcinoma.

Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer

Abstract: Specific chromosomal deletions sometimes associated with tumours such as retinoblastoma (chromosome 13q14)1 and Wilm's tumour (chromosome 11p13)2 have led to the hypothesis that recessive genes may be involved in tumorigenesis3. This hypothesis is supported by demonstration of allele loss specific for these regions using polymorphic DNA markers4–9 and by the isolation of a complementary DNA clone for the retinoblastoma gene10. A cytogenetic deletion in chromosome 3 (p14–p23) was reported in small-cell lung cancer (SCLC) by Whang-Peng et al11,12. At least one homologue of chromosome 3 was affected in the majority of SCLC tumours; however, the multiple chromosomal changes seen presented the possibility that chromosome 3 was rearranged, not deleted. We used polymorphic DNA probes for chromosome 3p and compared tumour and constitutional genotypes of nine SCLC patients. Our data show loss of alleles of chromosome 3p markers in tumour DNA of all nine patients supporting the hypothesis that this region contributes to tumorigenesis in SCLC.

Introduction of a normal human chromosome 11 into a Wilms' tumor cell line controls its tumorigenic expression.

Abstract: The development of Wilms' tumor, a pediatric nephroblastoma, has been associated with a deletion in the p13 region of chromosome 11. The structure and function or functions of this deleted genetic material are unknown. The role of this deletion in the process of malignant transformation was investigated by introducing a normal human chromosome 11 into a Wilms' tumor cell line by means of the microcell transfer technique. These variant cells, derived by microcell hybridization, expressed similar transformed traits in culture as the parental cell line. Furthermore, expression of several proto-oncogenes by the parental cells was unaffected by the introduction of this chromosome. However, the ability of these cells to form tumors in nude mice was completely suppressed. Transfer of other chromosomes, namely X and 13, had no effect on the tumorigenicity of the Wilms' tumor cells. These studies provide support for the existence of genetic information on chromosome 11 which can control the malignant expression of Wilms' tumor cells.

Genetic engineering of the cyanobacterial chromosome

Abstract: Publisher Summary This chapter describes methods for the direct genetic engineering of the cyanobacterial chromosome and techniques for the analysis of DNA and RNA from the resulting transformants. The DNA in lane B described in the chapter is a by-product of the RNA isolation procedure. The genetic engineering of the cyanobacterial chromosome includes the techniques described in the chapter. The chapter focuses on methods that employ wholly homologous transforming DNA or heterologous sequences, which are flanked by cyanobacterial DNA on either side. The analysis of DNA from transformants is necessary to determine the chromosomal structure following recombination. The recombination events illustrated in the chapter are those that are usually seen, but aberrant events have been observed when the cloned region homologous to the chromosome is small. These events include the deletion of a chromosomal segment and integration at a related locus in the case of a gene family. Southern hybridization can determine whether the expected event has in fact, occurred. It is also important to analyze RNA from transformants, which have been engineered by these methods. A homologous recombination event, which replaces a wild-type gene with another functional allele, should result in the production of a full-length mitochondrial RNA (mRNA), which initiates and terminates properly. The chapter also mentions the instructions of the procedure that describe the preparation of glass fines used in the cyanobacterial total DNA miniprep procedure, which was adapted from the method of Vogelstein and Gillespie.

Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia

Abstract: The somatic loss of heterozygosity for normal alleles occurring in human tumors has suggested the presence of recessive oncogenes. The results presented here demonstrate a loss of heterozygosity of several genes on chromosome 11 in primary breast tumors. Restriction fragment length polymorphism analysis of these DNAs further suggests that the most frequent loss of sequences in breast tumors occurs between the beta-globin and parathyroid hormone loci on the short arm of chromosome 11. The loss of heterozygosity for chromosome 11 loci has a significant association with tumors that lack estrogen and progesterone receptors, grade III tumors, and distal metastasis.

Human chromosome-specific repetitive DNA sequences: novel markers for genetic analysis

Abstract: Two recombinant DNA clones that are localized to single human chromosomes were isolated from a human repetitive DNA library. Clone pHuR 98, a variant satellite 3 sequence, specifically hybridizes to chromosome position 9qh. Clone pHuR 195, a variant satellite 2 sequence, specifically hybridizes to chromosome position 16qh. These locations were determined by fluorescent in situ hybridization to metaphase chromosomes, and confirmed by DNA hybridizations to human chromosomes sorted by flow cytometry. Pulsed field gel electrophoresis analysis indicated that both sequences exist in the genome as large DNA blocks. In situ hybridization to intact interphase nuclei showed a well-defined, localized organization for both DNA sequences. The ability to tag specific human autosomal chromosomes, both at metaphase and in interphase nuclei, allows novel molecular cytogenetic analyses in numerous basic research and clinical studies.

Arm homoeology of wheat and rye chromosomes

Abstract: Meiotic pairing was studied at metaphase I in three different cv. Chinese Spring × rye hybrid combinations (5B deficient, 3D deficient, and normal ABDR) to establish the arm homoeology of wheat and rye chromosomes. The majority of individual wheat chromosomes and their arms, as well as the arms of chromosomes 1R and 5R, were identified by means of C-banding. The results on pairing relationships support the genome reallocation of chromosomes 4A and 4B. The short arms of wheat chromosomes belonging to homoeologous groups 1, 3, 5, and 6 and of chromosome pairs 4A–4D and 7A–7D showed full pairing homoeology as well as the long arms of wheat chromosomes of groups 1, 3, 6, and 7 and of chromosome pairs 4A–4D and 5B–5D. Chromosomes 2A, 2B, and 2D were homoeologous, but the homoeologies of their arms were not identified. Reduced homoeologies of the 4BL arm to 7AS and 7DS, of the 5AL arm to 4AL and 4DL, and of the 7BS arm to 5BL and 5DL were identified. Arms 4BL, 5AL, and 7BS are involved in a double translocation...

Genomic organization of alpha satellite DNA on human chromosome 7: evidence for two distinct alphoid domains on a single chromosome.

Abstract: A complete understanding of chromosomal disjunction during mitosis and meiosis in complex genomes such as the human genome awaits detailed characterization of both the molecular structure and genetic behavior of the centromeric regions of chromosomes. Such analyses in turn require knowledge of the organization and nature of DNA sequences associated with centromeres. The most prominent class of centromeric DNA sequences in the human genome is the alpha satellite family of tandemly repeated DNA, which is organized as distinct chromosomal subsets. Each subset is characterized by a particular multimeric higher-order repeat unit consisting of tandemly reiterated, diverged alpha satellite monomers of approximately 171 base pairs. The higher-order repeat units are themselves tandemly reiterated and represent the most recently amplified or fixed alphoid sequences. We present evidence that there are at least two independent domains of alpha satellite DNA on chromosome 7, each characterized by their own distinct higher-order repeat structure. We determined the complete nucleotide sequences of a 6-monomer higher-order repeat unit, which is present in approximately 500 copies per chromosome 7, as well as those of a less-abundant (approximately 10 copies) 16-monomer higher-order repeat unit. Sequence analysis indicated that these repeats are evolutionarily distinct. Genomic hybridization experiments established that each is maintained in relatively homogeneous tandem arrays with no detectable interspersion. We propose mechanisms by which multiple unrelated higher-order repeat domains may be formed and maintained within a single chromosomal subset.

Chromosomal location of a K/Na discrimination character in the D genome of wheat.

Abstract: K/Na ratios have been determined in the leaves of salt-treated plants of 14 disomic substitution lines in which each of the D-genome chromosomes replaces the homoeologous A- or B-genome chromosome in the tetraploid wheat variety Langdon (AABB genome). Aneuploid lines of hexaploid bread wheat (cv Chinese Spring) having a reduced or an enhanced complement of chromosome 4D have also been examined. These investigations show that the gene(s) determining K/Na ratios in the leaves of wheat plants grown in the presence of salt is located on the long arm of chromosome 4D.

Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners.

Abstract: To elucidate the mechanism of the t(14;18)(q32;q21) chromosomal translocation found in follicular lymphoma, we examined the structure of both derivative (der) chromosomal breakpoints as well as their germ-line predecessors. We noted that chromosome segment 18q21 was juxtaposed with immunoglobulin heavy (H) chain gene diversity (DH) regions on all five der(18) chromosomes we examined, and we confirmed the juncture with immunoglobulin H-chain gene joining (JH) regions on the der(14) chromosome. However, the t(14;18) was not fully reciprocal in that chromosome 14 DNA between the DH and JH regions was deleted. Furthermore, extra nucleotides, reminiscent of "N" segments, were present at the der(14) and possibly der(18) junctions. This indicates that despite the mature B-cell phenotype of follicular lymphoma, the t(14;18) occurs during attempted DH-JH joining, the earliest event in immunoglobulin rearrangement in a pre-B-cell. Our detailed analysis of the germ-line 18q21 region indicated that most breakpoints clustered within a 150-base-pair major breakpoint region. However, we found no evidence for evolutionarily conserved immunoglobulin-like recombinational signals at 18q21, arguing against a role for immunoglobulin recombinase in chromosome 18 breakage. Instead, a direct repeat duplication of chromosome 18 sequences was discovered at both chromosomal junctures, typical of the repair of a naturally occurring staggered double-stranded DNA break. These results prompt a translocation model with illegitimate pairing of a staggered double-stranded DNA break at 18q21 and an immunoglobulin endonuclease-mediated break at 14q32 and with N-segment addition, repair, and ligation to generate der(14) and der(18) chromosomes.

Genetic manipulation of centromere function.

Abstract: A conditional centromere was constructed in Saccharomyces cerevisiae by placing the centromere of chromosome III immediately downstream from the inducible GAL1 promoter from S. cerevisiae. By utilizing growth conditions that favor either transcriptional induction (galactose-carbon source) or repression (glucose-carbon source) from the GAL1 promoter, centromere function can be switched off or on, respectively. With the conditional centromere we were able to radically alter the mitotic transmission pattern of both monocentric and dicentric plasmids. Moreover, it was possible to selectively induce the loss of a single chromosome from a mitotically dividing population of cells. We observed that the induction of chromosome III aneuploidy resulted in a dramatic change in cell morphology. The construction of a conditional centromere represents a novel way to create conditional mutations of cis-acting DNA elements and will be useful for further analysis of this important stabilizing element.

Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation.

Abstract: The human RCCI gene was cloned after DNA-mediated gene transfer into the tsBN2 cell line, which shows premature chromosome condensation at nonpermissive temperatures (39.5-40°C). This gene codes for a 2.5-kb poly(A) + RNA that is well conserved in hamsters and humans. We isolated 15 cDNA clones from the Okayama-Berg human cDNA library, and found two that can complement the tsBN2 mutation with an efficiency comparable to that of the genomic DNA clone. The base sequences of these two active cDNA clones differ at the 5' proximal end, yet both have a common open reading frame, encoding a protein of 421 amino acids with a calculated molecular weight of 44,847 and with seven homologous repeated domains of about 60 amino acids. This human RCC1 gene was located to human chromosome 1 using sorted chromosomal fractions.

Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13.

Abstract: The genotypes at chromosomal loci defined by recombinant DNA probes revealing restriction fragment length polymorphisms were determined in constitutional and tumor tissue from 10 cases of ductal breast cancer: eight premenopausal females and two males. Somatic loss of constitutional heterozygosity was observed at loci on chromosome 13 in primary tumor tissue from three females and one male. In two cases, specific loss of heterozygosity at three distinct genetic loci along the length of the chromosome was observed. In another case, concurrent loss of alleles at loci on chromosomes 2, 13, 14, and 20 was detected, whereas a fourth case showed loss of heterozygosity for chromosomes 5 and 13. In each instance, the data were consistent with loss of one of the homologous chromosomes by mitotic nondisjunction. Analysis of loci on several other chromosomes showed retention of constitutional heterozygosity suggesting the relative specificity of the events. In contrast, similar analyses of other breast cancers, including comedocarcinoma, medullary carcinoma, and juvenile secretory carcinoma, showed no loss of alleles at loci on chromosome 13. These data indicate that the pathogenesis of ductal breast cancer may, in a substantial proportion of cases, involve unmasking of a recessive locus on chromosome 13 and suggest the involvement of such a locus in heritable forms of this disease.

Hypothesis: some mutagens directly alter specific chromosomal proteins (DNA topoisomerase II and peripheral proteins) to produce chromosome stickiness, which causes chromosome aberrations

Abstract: Recent biochemical and molecular biological data on the composition and structure of the chromosome and the nucleus, combined with observations on the chromosomes of mutant yeast cells and grasshopper neuroblasts, offer new perspectives on mutagen-induced chromosome stickiness and its relation to chromosome breakage. A hypothesis consistent with these data states that chromosome stickiness (i) results from changes in specific non-histone proteins (topoisomerase II and the peripheral proteins) that are integral components of the chromosome and whose function is necessary for separation and segregation of chromatids, the changes being caused either by mutation in structural genes for the proteins (heritable stickiness) or by direct action of mutagens on the proteins (induced stickiness); (ii) occurs in various degrees (slight, moderate, severe, extreme) that are determined by the number of target protein molecules affected, a certain number (threshold) of affected molecules at a given site on a chromosome being required to resist the forces of anaphase movement in order to produce microscopically detectable stickiness; (iii) results from molecular events that can occur at several phases of the cell cycle (including interphase), but can only be recognized at prometaphase, metaphase and anaphase; and (iv) causes chromosome aberrations by the physical stretching and breaking of chromatids at the sticky sites; hence the breakage resulting from stickiness is a secondary effect that requires anaphase movement, in contrast to breakage resulting from direct action of mutagens on DNA.

Chromosomal integration sites of human papillomavirus DNA in three cervical cancer cell lines mapped by in situ hybridization

Abstract: Metaphase chromosomes of three cervical cancer cell lines (HeLa, CasKi, SiHa) were subjected to in situ hybridizations with the DNA of human papillomaviruses (HPV) types 16 and 18, respectively. Previous studies have demonstrated multiple copies of HPV 18 DNA in HeLa and of HPV 16 DNA in CasKi cells, but only 1-2 HPV 16 copies in cells of the SiHa line. The viral DNA persists in an integrated state (Schwarz et al 1985). Analysis of the integration sites revealed at least 11 chromosomal sites of HPV 16 integration in CasKi cells. SiHa cells contain integrated HPV 16 DNA in the region q21-q31 of chromosome No. 13. In HeLa cells integration of HPV 18 occurred in chromosome No. 8, band q24. Thus, no evidence was obtained for the existence of preferential chromosomal regions for HPV integration. The data indirectly support a trans-acting function of HPV-mediated cell transformation.

The nucleotide and deduced amino acid sequences of an HMW glutenin subunit gene from chromosome 1B of bread wheat ( Triticum aestivum L.) and comparison with those of genes from chromosomes 1A and 1D

Abstract: The nucleotide and deduced amino acid sequences of a high molecular weight glutenin subunit gene derived from chromosome 1B of bread wheat (Triticum aestivum L) are reported The encoded protein corresponds to the y-type subunit 1B9 Comparison of the 5′ upstream untranslated regions of this gene and a previously reported silent y-type gene derived from chromosome 1A showed a deletion of 85 bp in the latter A sequence present in this region of the 1By 9 gene shows homology with part of the “-300 element” which is conserved in the 5′ upstream regions of other prolamin genes from barley, wheat and maize (Forde BG et al 1985) It is suggested that the absence of this element is responsible for the lack of expression of the 1Ay gene Comparison of the derived amino acid sequence with those reported previously for the silent 1Ay gene and the expressed x-type (1Dx2) and y-type (1Dy12) genes derived from chromosome 1D showed that the three y-type proteins are closely related In contrast the x-type subunit (1Dx2) shows clear differences in the N-terminal region and in the number, type and organisation of repeats in the central repetitive domain

The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q.

Abstract: The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, we localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33 [del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent form the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF (the gene encoding granulocyte-macrophage-CSF), CSF-1 (the gene encoding macrophage-CSF), and FMS (the human c-fms protooncogene, which encodes the CSF-1 receptor). Our findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q-chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).

Human chromosomes 6 and 21 are required for sensitivity to human interferon. gamma

Abstract: The human interferon gamma receptor has previously been assigned to chromosome 6. Chromosome 6 also encodes HLA, the human class I major histocompatibility antigens. However, the presence of chromosome 6 in hamster-human hybrids is by itself insufficient to confer sensitivity to human immune interferon as measured by the induction of human HLA. Human chromosome 21 was found to be the second chromosome essential for HLA inducibility. Similar results were found with mouse-human somatic cell hybrids. Thus, at least two steps are involved in the action of human interferon gamma: the binding of interferon gamma to its receptor coded by chromosome 6 and the linkage of this binding event through a factor coded by chromosome 21 to trigger biological action. Both of these steps are species-specific.

Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders

Abstract: The CSF-1 gene encodes a hematopoietic colony-stimulating factor (CSF) that promotes growth, differentiation, and survival of mononuclear phagocytes. By using somatic cell hybrids and in situ hybridization, we localized this gene to human chromosome 5 at bands q31 to q35, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the CSF-1 gene was found to be deleted in the 5q- chromosome of a patient with refractory anemia who had a del(5)(q15q33.3) and in that of a second patient with acute nonlymphocytic leukemia de novo who had a similar distal breakpoint [del(5)(q13q33.3)]. The gene was present in the deleted chromosome of a third patient, with therapy-related acute nonlymphocytic leukemia, who had a more proximal breakpoint in band q33 [del(5)(q22q33.1)]. Hybridization of the CSF-1 probe to metaphase cells of a fourth patient, with acute nonlymphocytic leukemia de novo, who had a rearrangement of chromosomes 5 and 21 [ins(21;5)(q22;q31.3q33.1)] resulted in labeling of the breakpoint junctions of both rearranged chromosomes; this suggested that CSF-1 is located at 5q33.1. Thus, a small segment of chromosome 5 contains GM-CSF (the gene encoding the granulocyte-macrophage CSF), CSF-1, and FMS, which encodes the CSF-1 receptor, in that order from the centromere; this cluster of genes may be involved in the altered hematopoiesis associated with a deletion of 5q.

DNA Sequence and Regional Assignment of the Human Follicle-Stimulating Hormone β-Subunit Gene to the Short Arm of Human Chromosome 11

Abstract: A human genomic DNA fragment in phage λ containing FSHB, the gene for the β-subunit of human follicle-stimulating hormone (FSH-β), was analyzed and the nucleotide sequence of the region of the clone encoding FSH-β was determined. A subclone of the λ phage containing 67% of FSH-β coding sequence was used as hybridization probe to determine the human chromosomal location of FSHB. A panel of mouse-human somatic cell hybrids containing reduced numbers of human chromosomes was screened with the FSHB probe; complete cosegregation of FSHB with human chromosome 11 was observed in all 26 cell hybrids tested. Analysis of a set of cell hybrids containing translocated derivatives of chromosome 11 further localized FSHB to the human chromosome region llpll.2→11pter. A Hind III restriction fragment length polymorphism (RFLP) detected by another subclone of the λ phage containing FSHB now provides a genetic marker for this region of the human genome.

Chromosome analysis of human oocytes recovered from preovulatory follicles in stimulated cycles.

Abstract: To investigate the incidence and types of abnormalities of chromosome number in oocytes, we recovered preovulatory oocytes from 17 women who were undergoing clomiphene stimulation and laparoscopy because of infertility. Twenty-three oocytes were recovered and studied after they had been fixed with a gradualfixation method: 17 of the oocytes had numbers of chromosomes in the haploid range (19 to 25 second-metaphase chromosomes), 4 had only 1 to 5 chromosomes, 1 was not analyzable, and 1 had 23 chromosome bivalents in the first metaphase. Of the oocytes with chromosome numbers in the haploid range, nine had an apparently normal haploid set of 23 chromosomes. Two had 1 to 2 additional chromosomes, three lacked 2 to 4 chromosomes, and three had totals of chromosomes that were close to 23 but could not be determined with certainty. We conclude that infertile women undergoing clomiphene stimulation have a high proportion (nearly 50 percent) of oocytes with an abnormal karyotype. If this is also true of...

Three-dimensional organization of Drosophila melanogaster interphase nuclei. I: Tissue-specific aspects of polytene nuclear architecture

Abstract: Interphase chromosome organization in four different Drosophila melanogaster tissues, covering three to four levels of polyteny, has been analyzed. The results are based primarily on three-dimensional reconstructions from unfixed tissues using a computer-based data collection and modeling system. A characteristic organization of chromosomes in each cell type is observed, independent of polyteny, with some packing motifs common to several or all tissues and others tissue-specific. All chromosomes display a right-handed coiling chirality, despite large differences in size and degree of coiling. Conversely, in each cell type, the heterochromatic centromeric regions have a unique structure, tendency to associate, and intranuclear location. The organization of condensed nucleolar chromatin is also tissue-specific. The tightly coiled prothoracic gland chromosomes are arrayed in a similar fashion to the much larger salivary gland chromosomes described previously, having polarized orientations, nonintertwined spatial domains, and close packing of the arms of each autosome, whereas hindgut and especially the unusually straight midgut chromosomes display striking departures from these regularities. Surprisingly, gut chromosomes often appear to be broken in the centric heterochromatin. Severe deformations of midgut nuclei observed during gut contractions in living larvae may account for their unusual properties. Finally, morphometric measurements of chromosome and nuclear dimensions provide insights into chromosome growth and substructure and also suggest an unexpected parallel with diploid chromatin organization.

The hypervariable gene locus PUM, which codes for the tumour associated epithelial mucins, is located on chromosome 1, within the region 1g21–24

Abstract: A single hypervariable autosomal gene locus, PUM, codes for a family of mucin-type glycoproteins present in human urine, and in several other normal and malignant tissues of epithelial origin. These mucins can be detected after electrophoresis using a series of monoclonal antibodies that show a pronounced tumour specificity on immunohistochemistry. Using a recently cloned cDNA, pMUC10, coding for the core protein of the PUM coded mucins, to probe DNA isolated from a series of human-rodent somatic cell hybrids, we have assigned the PUM locus to chromosome 1. This assignment was confirmed by in situ hybridization of pMUC10 to lymphocyte metaphase chromosomes and the gene was shown to be located within the region 1q21-24.