DOCSLIB.ORG

A Comparison of the Huntington's Disease Associated Trinucleotide

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Comparison of the Huntington's Disease Associated Trinucleotide 40440 Med Genet 1995;32:404-408 sponsible for HD has important implications one expanded allele were found in all HD for both research and clinical practice. How- patients. The comparison ofthe size variation LETTERS TO ever, most of the data relate to white pop- of triplet repeats in the control and HD chro- ulations. In this study we verify the presence mosomes between Chinese and whites is of the trinucleotide repeat elongation in Chi- shown in the table. Thirteen discrete allele THE EDITOR J Med Genet: first published as 10.1136/jmg.32.5.404 on 1 May 1995. Downloaded from nese patients with HD and establish the range sizes among the normal population, with a ofrepeat sizes in affected and normal subjects. heterozygosity frequency of 80-7%, and an The diagnosis of HD was based on clinical expanded range from 40 to 58 copies on HD and family histories, neurological ex- chromosomes, were found. The peaks of the aminations, and special investigations, such normal and HD ranges were well separated A comparison of the as electroencephalography and computerised at 17 and 43 repeats, respectively, and no Huntington's disease tomography. Genomic DNA samples were overlap of the two distributions was observed available from a total of 114 persons (51 (figure). Within our population, 65-7% ofthe associated trinucleotide normal controls and 63 members of 11 un- expanded alleles fell in the range of 40 to 45 repeat between Chinese related HD families, including 11 unrelated repeats, while only 17-1% consisted of more spouses who also served as controls). than 50 units. and white populations The size of the (CAG)n trinucleotide This is the first study examining the HD repeat was analysed by the polymerase chain mutation in a large Chinese population. The Huntington's disease (HD) affects one in reaction (PCR). The genomic primer se- range ofthe CAG repeat length of 159 control 10000 people in most white populations.12 quences used in our PCR assay for the chromosomes (124 from 51 normal subjects Its prevalence among the Chinese is not clear, (CAG)n repeat were HD-1: 5' ATG AAG and 11 unrelated spouses of the HD patients; but it is not expected to be much different GCC TTC GAG TCC CTC AAG TCC 35 from the affected or presymptomatic sub- from that of the white population. In 1993, TTC 3', and HD-3: 5' GGC GGT GGC jects, each having one chromosome that did a polymorphic (CAG)n trinucleotide repeat GGC TGT TGC TGC TGC TGC TGC not contain the expanded CAG repeat) was was identified3 in the 5' region of a new 3'.' The PCR assay was performed as de- nine to 29, with a median of 17 repeats transcript, IT1 5. The protein encoded by the scribed by Warner et al8 with minor mo- (figure, table). The normal allele distribution IT15 was named huntingtin.3 The ob- difications. of the polymorphic (CAG)n repeat in the servation that the length of the trinucleotide The PCR assay was highly specific and huntingtin gene among the Chinese popu- repeat was increased in virtually all HD chro- gave products in the 74 base pairs (bp) (nine lation is much tighter (with a statistically mosomes examined,46 as well as in families CAG repeats) to 134bp (29 CAG repeats) significant smaller standard deviation) than with a presumed new mutation,7 suggests the range from normal chromosomes, and prod- the distributions reported in the United mutational mechanism causing HD has been ucts of 167bp (40 repeats) and larger from States46 and Europe5 9-12 (table). The dis- identified. The discovery of the mutation re- HD chromosomes (figure). One normal and tribution looks more like the recently pub- lished African and Japanese distributions where there is a lower incidence of HD.4 The median of the size of the upper alleles representing the expanded HD chromosomes was 44 repeats, with a range of 40 to 58 (figure, table). All Chinese patients in whom HD was diagnosed were heterozygous, with one allele in the normal range and one ex- panded allele, indicating that expansion of this (CAG)n repeat is the major cause of Huntington's disease. A copy number of 40 or higher can result in the full phenotypic http://jmg.bmj.com/ manifestations of the disease. Thus, muta- 0- tional events leading to HD seem to be c 30 a) homogeneous worldwide.4'9-12 The finding that the molecular biology of HD is in- distinguishable in Chinese and white pop- LL ulations is of great interest. The idea that 20 worldwide HD evolved from a very limited number of European founders is no longer tenable.41314 This study provides evidence on September 28, 2021 by guest. Protected copyright. 10 that there is a basal rate of susceptibility to the HD mutation constantly adding new families. It will be very interesting to know whether new mutation rates differ between o races. 5 10 15 20 25 30 35 40 45 50 55 60 MacMillan et all' and Kremer et al4 re- Repeat units ported an estimated sensitivity of 98% and a specificity of 100% for the use of the number Distribution of absolute frequencies of trinucleotide repeat number in 159 independent control of CAG repeats to identify those with the chromosomes (shaded bars) and 35 HD chromosomes (open bars) among the Chinese. mutation for HD. The diagnostic value ofthe trinucleotide repeat expansion is apparently high within our population, with no overlap in Comparison of the distributions of triplet repeats in the control and HD chromosomes in the Chinese values between normal and affected persons. and white populations This molecular test can be used to differ- entiate from Boston Cardiff Vancouver Taipei HD other illnesses.'617 We have (Duyao et a16) (Snell et a15) (Kremer et al') (This study) not encountered any patient with the clinical phenotype of HD without the trinucleotide Normal controls 545 1160 600 159 expansion. Moreover, the ability to measure Range of repeat numbers 11-34 9-34 10-39 9-29 Mean 19-71 18 29 18-4 17-36* the size of the trinucleotide repeat in people Median 19 18 17 at risk for HD will revolutionise preclinical SD 3-21 3-13 1-97 testing and eliminate the need for linkage HD mutant genes 425 440 995 35 analysis. This will greatly facilitate Range of repeat numbers 37-86 16-70 36-121 40-58 coun- Mean 46-42 41-88 45-3 44-94t selling and makes the test available to ap- Median 45 44 44 plicants without living relatives, and without SD 6-68 6-67 4-15 undue involvement of other at risk sibs. We believe that the ethical and social * p<O-OOl for the comparison with the Boston group, and p<001 for the comparison with the Cardiff issues in- group, by Student's t test. volved will remain largely unchanged; they t p<0-01 for the comparison with the Cardiff group, by Student's t test. may well become more important as the Letters to the Editor 405 laboratory aspects are simplified. Accepted Rare variants of chromosome 9 (figs 1 and 2). Again, as in international guidelines and counselling pro- the AluI treatment, the result was the opposite tocols should be adhered to when using direct chromosome 9 with extra of that of Fernandez et al and showed that repeat size determination in doing pre- G positive band within the the extra band was not affected and remained symptomatic or prenatal testing.'8 condensed. The induction of J Med Genet: first published as 10.1136/jmg.32.5.404 on 1 May 1995. Downloaded from are 5-azacytidine qh region not alike (3-5 x 1i0- mol/1) during the last seven hours We would like to thank Dr Tsung-sheng Su for her of incubation apparently hypomethylates the helpful discussions on this manuscript. We are also The intriguing findings in a recent in- late classical satellite constitutive indebted to replicating Wen-yung Sheng, MPH, for her con- Fernandez et al' us tribution to the statistical analysis. Furthermore we vestigation by prompted heterochromatin regions of chromosomes want to thank all HD patients for providing samples to re-evaluate our previous case2 that had a 1, 9, 15, 16, and Y, and causes under- for scientific research. The work was supported similar extra G positive band within the 9qh condensation owing to its incorporation by grants from the National Science Council, the additional molecular this It is Republic of China (NSC 83-0412-B075-077-M02, region by techniques. during period.56 believed the un- NSC 84-233 1-B075-062-M02), and partly from the To our knowledge, these two studies, in ad- dercondensation of the heterochromatin that Yen Tjing-Ling Medical Foundation (CI-77-32, CI- dition to a third by Macera et al,' are the is caused by the induction of 5-azacytidine is 78-34, CI-81-11). only ones that have used various molecular possible owing to the relatively high variation techniques which showed satellite DNA loc- in the number of repeated units within the BING-WEN SOONG ations in this particular so-called rare variant classical satellite DNA region; generally this Department of Neurology, of chromosome 9. other which is not the case in the and beta satellite National Defense Medical Center and Many reports alpha National Yang-Ming University School of Medicine. have focused on this seeming paradox, stated DNA of chromosome 9.4 However, it has BING-WEN SOONG that the variant chromosome 9 appeared to be been shown that there are differences in the JIH-TSWU WANG similar by conventional banding condensation inhibition behaviour of cen- Department of Neurology, Neurological Institute, techniques.
Load more

Recommended publications
  • Staphylococcus Aureus Cas9 for Simultaneous
    Published online 5 January 2016 Nucleic Acids Research, 2016, Vol. 44, No. 8 e75 doi: 10.1093/nar/gkv1533 Expanding the CRISPR imaging toolset with Staphylococcus aureus Cas9 for simultaneous imaging of multiple genomic loci Baohui Chen1, Jeffrey Hu1, Ricardo Almeida2, Harrison Liu3, Sanjeev Balakrishnan4, Christian Covill-Cooke5, Wendell A. Lim2,6 and Bo Huang1,7,* 1Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA, 2Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA, 3Graduate Program of Bioengineering, University of California, San Francisco, San Francisco, CA 94143, USA, 4Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA, 5MRC Laboratory of Molecular Cell Biology, University College London, London, WC1E 6BT, UK, 6Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 4143, USA and 7Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA Received August 20, 2015; Revised November 24, 2015; Accepted December 22, 2015 ABSTRACT fold that interacts with Cas9 (15–18). Target recognition by the Cas9-sgRNA complex requires Watson–Crick base In order to elucidate the functional organization of pairing with the 5 end of the sgRNA (≈20 nt) as well as the genome, it is vital to directly visualize the interac- a short protospacer-adjacent motif (PAM) located imme- tions between genomic elements in living cells. For diately downstream of the target DNA sequence (13,19– this purpose, we engineered the Cas9 protein from 21). The PAM sequences are diverse among orthologous Staphylococcus aureus (SaCas9) for the imaging of CRISPR-Cas systems.
    [Show full text]
  • Evaluating the Probability of CRISPR-Based Gene Drive Contaminating Another Species
    bioRxiv preprint doi: https://doi.org/10.1101/776609; this version posted September 19, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Evaluating the Probability of CRISPR-based Gene Drive Contaminating Another Species 1 2 3 4 Virginie Courtier-Orgogozo ,​ Antoine Danchin ,​ Pierre-Henri Gouyon ​ and Christophe Boëte ​ ​ ​ ​ 1 I​ nstitut Jacques Monod, CNRS, UMR 7592, Université de Paris, Paris, France 2 I​ nstitut Cochin INSERM U1016 – CNRS UMR8104 – Université Paris Descartes, Paris, France 3 I​ nstitut de Systématique, Évolution, Biodiversité, Muséum National d'Histoire Naturelle, CNRS, Sorbonne Université, EPHE, UA, Paris, France 4 I​ SEM, Université de Montpellier, CNRS, IRD, EPHE, Montpellier, France Abstract The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = (hyb+transf).express.cut.flank.immune.nonextinct with ​ ​ hyb = probability of hybridization between the target species and a non-target species ​ transf = probability of horizontal transfer of a piece of DNA containing the gene drive ​ cassette from the target species to a non-target species (with no hybridization) express = probability that the Cas9 and guide RNA genes are expressed ​ ​ ​ cut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the ​ new host flank = probability that the gene drive cassette inserts at the cut site ​ immune = probability that the immune system does not reject Cas9-expressing cells ​ ​ ​ nonextinct = probability of invasion of the drive within the population ​ We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans.
    [Show full text]
  • Repetitive Elements in Humans
    International Journal of Molecular Sciences Review Repetitive Elements in Humans Thomas Liehr Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Am Klinikum 1, D-07747 Jena, Germany; [email protected] Abstract: Repetitive DNA in humans is still widely considered to be meaningless, and variations within this part of the genome are generally considered to be harmless to the carrier. In contrast, for euchromatic variation, one becomes more careful in classifying inter-individual differences as meaningless and rather tends to see them as possible influencers of the so-called ‘genetic background’, being able to at least potentially influence disease susceptibilities. Here, the known ‘bad boys’ among repetitive DNAs are reviewed. Variable numbers of tandem repeats (VNTRs = micro- and minisatellites), small-scale repetitive elements (SSREs) and even chromosomal heteromorphisms (CHs) may therefore have direct or indirect influences on human diseases and susceptibilities. Summarizing this specific aspect here for the first time should contribute to stimulating more research on human repetitive DNA. It should also become clear that these kinds of studies must be done at all available levels of resolution, i.e., from the base pair to chromosomal level and, importantly, the epigenetic level, as well. Keywords: variable numbers of tandem repeats (VNTRs); microsatellites; minisatellites; small-scale repetitive elements (SSREs); chromosomal heteromorphisms (CHs); higher-order repeat (HOR); retroviral DNA 1. Introduction Citation: Liehr, T. Repetitive In humans, like in other higher species, the genome of one individual never looks 100% Elements in Humans. Int. J. Mol. Sci. alike to another one [1], even among those of the same gender or between monozygotic 2021, 22, 2072.
    [Show full text]
  • Genome Organization/ Human
    Genome Organization/ Secondary article Human Article Contents . Introduction David H Kass, Eastern Michigan University, Ypsilanti, Michigan, USA . Sequence Complexity Mark A Batzer, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA . Single-copy Sequences . Repetitive Sequences . The human nuclear genome is a highly complex arrangement of two sets of 23 Macrosatellites, Minisatellites and Microsatellites . chromosomes, or DNA molecules. There are various types of DNA sequences and Gene Families . chromosomal arrangements, including single-copy protein-encoding genes, repetitive Gene Superfamilies . sequences and spacer DNA. Transposable Elements . Pseudogenes . Mitochondrial Genome Introduction . Genome Evolution . Acknowledgements The human nuclear genome contains 3000 million base pairs (bp) of DNA, of which only an estimated 3% possess protein-encoding sequences. As shown in Figure 1, the DNA sequences of the eukaryotic genome can be classified sequences such as the ribosomal RNA genes. Repetitive into several types, including single-copy protein-encoding sequences with no known function include the various genes, DNA that is present in more than one copy highly repeated satellite families, and the dispersed, (repetitive sequences) and intergenic (spacer) DNA. The moderately repeated transposable element families. The most complex of these are the repetitive sequences, some of remainder of the genome consists of spacer DNA, which is which are functional and some of which are without simply a broad category of undefined DNA sequences. function. Functional repetitive sequences are classified into The human nuclear genome consists of 23 pairs of dispersed and/or tandemly repeated gene families that chromosomes, or 46 DNA molecules, of differing sizes either encode proteins (and may include noncoding (Table 1).
    [Show full text]
  • A Monkey Alu Sequence Is Flanked by 13-Base-Pair Direct Repeats
    Proc. Natt Acad. Sci. USA Vol. 79, pp. 1497-1500, March 1982 Biochemistry A monkey Alu sequence is flanked by 13-base-pair direct repeats of an interrupted a-satellite DNA sequence (transposable element/repeated DNA/DNA sequence analysis) GIOVANNA GRIMALDI AND MAXINE F. SINGER Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Building 37, Room 4E-28, Bethesda, Maryland 20205 Contributed by Maxine F. Singer, December 11, 1981 ABSTRACT A member of the Alu family, the dominant family (16) supplied by Carl Schmid and Prescott Deininger; the se- of short interspersed repeated DNA sequences in primates, in- quence ofthis Alu is known (16). The conditions for hybridiza- terrupts a cloned repeat unit of African green monkey a-satellite tion were 0.05 M phosphate. buffer, pH 6.5/0.45 M NaCl/ DNA. TheAlu is immediately flanked by 13-base-pair duplications 0.045 M sodium citrate/0.2% bovine albumin/0.2% Ficoll/ of the known sequence ofthe satellite at the site ofinsertion. These 0.2% polyvinylpyrrolidone/0. 1% sodium lauryl sulfate contain- observations support the idea that Alu family members may be ing 500 jug ofdenatured sheared salmon sperm DNA and =100 moveable elements. ng ofdenatured 32P-labeled probe (5 x 106 cpm) in a total vol- ume of30 ml for 16 hr at 650C. Filters were washed at 550C for The Alu family of short interspersed DNA sequences is reit- three 1-hr periods in 0.03 M NaCV3 mM sodium citrate/0. 1% erated =3 x 105 times in the genomes of humans (1-3) and sodium lauryl sulfate.
    [Show full text]
  • First Description of a Satellite DNA in Manatees' Centromeric Regions
    BRIEF RESEARCH REPORT published: 24 August 2021 doi: 10.3389/fgene.2021.694866 First Description of a Satellite DNA in Manatees’ Centromeric Regions Mirela Pelizaro Valeri 1, Guilherme Borges Dias 2, Alice Alves do Espírito Santo 1, Camila Nascimento Moreira 3, Yatiyo Yonenaga-Yassuda 3, Iara Braga Sommer 4, Gustavo C. S. Kuhn 1 and Marta Svartman 1* 1 Laboratório de Citogenômica Evolutiva, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 2 Department of Genetics and Institute of Bioinformatics, University of Georgia, Athens, GA, United States, 3 Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil, 4 Centro Nacional de Pesquisa e Conservação da Biodiversidade Marinha do Nordeste, Instituto Chico Mendes de Conservação da Biodiversidade, Brasília, Brazil Trichechus manatus and Trichechus inunguis are the two Sirenia species that occur in the Americas. Despite their increasing extinction risk, many aspects of their biology remain understudied, including the repetitive DNA fraction of their genomes. Here we used the sequenced genome of T. manatus and TAREAN to identify satellite DNAs (satDNAs) in this species. We report the first description of TMAsat, a satDNA comprising ~0.87% of Edited by: the genome, with ~684 bp monomers and centromeric localization. In T. inunguis, TMAsat Francisco J. Ruiz-Ruano, showed similar monomer length, chromosome localization and conserved CENP-B University of East Anglia, United Kingdom box-like motifs as in T. manatus. We also detected this satDNA in the Dugong dugon and Reviewed by: in the now extinct Hydrodamalis gigas genomes.
    [Show full text]
  • Genome-Wide Characterization of Satellite DNA Arrays in a Complex Plant Genome Using Nanopore Reads
    bioRxiv preprint doi: https://doi.org/10.1101/677575; this version posted June 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Genome-wide characterization of satellite DNA arrays in a complex plant genome using nanopore reads by Tihana Vondrak1,2, Laura Ávila Robledillo1,2, Petr Novák1, Andrea Koblížková1, Pavel Neumann1 and Jiří Macas1,* (1) Biology Centre, Czech Academy of Sciences, Branišovská 31, České Budějovice, CZ-37005, Czech Republic (2) University of South Bohemia, Faculty of Science, České Budějovice, Czech Republic * Corresponding author e-mail: [email protected] phone: +420 387775516 1 bioRxiv preprint doi: https://doi.org/10.1101/677575; this version posted June 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Abstract 2 Background: Amplification of monomer sequences into long contiguous arrays is the main 3 feature distinguishing satellite DNA from other tandem repeats, yet it is also the main obstacle in 4 its investigation because these arrays are in principle difficult to assemble. Here we explore an 5 alternative, assembly-free approach that utilizes ultra-long Oxford Nanopore reads to infer the 6 length distribution of satellite repeat arrays, their association with other repeats and the 7 prevailing sequence periodicities.
    [Show full text]
  • Heat Stress Affects H3k9me3 Level at Human Alpha Satellite DNA Repeats
    G C A T T A C G G C A T genes Article Heat Stress Affects H3K9me3 Level at Human Alpha Satellite DNA Repeats Isidoro Feliciello 1,2,* , Antonio Sermek 1, Željka Pezer 1, Maja Matuli´c 3 and Ðurdica¯ Ugarkovi´c 1,* 1 Department of Molecular Biology, Ruder Boškovi´cInstitute, Bijeniˇcka54, HR-10000 Zagreb, Croatia; [email protected] (A.S.); [email protected] (Z.P.) 2 Dipartimento di Medicina Clinica e Chirurgia, Universita0 degli Studi di Napoli Federico II, via Pansini 5, I-80131 Napoli, Italy 3 Department of Biology, Faculty of Science, University of Zagreb, HR-10000 Zagreb, Croatia; [email protected] * Correspondence: [email protected]; [email protected]; Tel.: +39-3495250441 (I.F.); +385-14561197 (D.U) Received: 26 May 2020; Accepted: 16 June 2020; Published: 18 June 2020 Abstract: Satellite DNAs are tandemly repeated sequences preferentially assembled into large arrays within constitutive heterochromatin and their transcription is often activated by stress conditions, particularly by heat stress. Bioinformatic analyses of sequenced genomes however reveal single repeats or short arrays of satellite DNAs dispersed in the vicinity of genes within euchromatin. Here, we analyze transcription of a major human alpha satellite DNA upon heat stress and follow the dynamics of “silent” H3K9me3 and “active” H3K4me2/3 histone marks at dispersed euchromatic and tandemly arranged heterochromatic alpha repeats. The results show H3K9me3 enrichment at alpha repeats upon heat stress, which correlates with the dynamics of alpha satellite DNA transcription activation, while no change in H3K4me2/3 level is detected. Spreading of H3K9me3 up to 1–2 kb from the insertion sites of the euchromatic alpha repeats is detected, revealing the alpha repeats as modulators of local chromatin structure.
    [Show full text]
  • Multiplicity of Satellite DNA Sequences in Drosophila Melanogaster (Repeated DNA/Heterochromatin/Clone Instability) ALLAN R
    Proc. Nati. Acad. Sci. USA Vol. 83, pp. 696-700, February 1986 Genetics Multiplicity of satellite DNA sequences in Drosophila melanogaster (repeated DNA/heterochromatin/clone instability) ALLAN R. LOHE* AND DOUGLAS L. BRUTLAGt Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305 Communicated by David S. Hogness, September 3, 1985 ABSTRACT Three Drosophila melanogaster satellite inserts of the same size ranges as the starting material, and DNAs (1.672, 1.686, and 1.705 g/ml in CsCl), each containing therefore showing no evidence for deletion, were sequenced a simple sequence repeated in tandem, were cloned in pBR322 (see Results). as small fragments about 500 base pairs long. This precaution We investigated the instability of clones derived from the minimized deletions, since inserts of the same size as the three simple satellite DNAs by varying the size of fragments fragments used for cloning were recovered in a stable form. A used for cloning. When small DNA segments (==500 bp) were homogeneous tandem array of one sequence type usually cloned in pBR322, fragments of the same size could be extended the length of the insert. Eleven distinct repeat recovered from the plasmids although the efficiency of sequences were discovered, but only one sequence was pre- cloning was low. Clones were sequenced to verify the fidelity dominant in each satellite preparation. The remaining classes of cloning and to identify the repeating sequence. Although were minor in amount. The repeat unit lengths were restricted each of the 1.672, 1.686, and 1.705 satellites is comprised to 5, 7, or 10 base pairs, with sequences closely related.
    [Show full text]
  • Telomere Replication, Kinetochore Organizers, and Satellite DNA Evolution (Centromere/Robertsonian Rearrangement) GERALD P
    Proc. Nati. Acad. Sci. USA Vol. 76, No. 9, pp. 4566-4570, September 1979 Genetics Telomere replication, kinetochore organizers, and satellite DNA evolution (centromere/Robertsonian rearrangement) GERALD P. HOLMQUIST* AND BARRY DANCISt *Kleberg Genetics Center, Department of Medicine, Baylor College of Medicine, 1200 Moursund Avenue, Houston, Texas 77030; and tDepartment of Biology, Temple University, Philadelphia, Pennsylvania 19122 Communicated by Ernest R. Sears, June 11, 1979 ABSTRACT Robertsonian rearrangements demonstrate 7, 8). In addition, Robertsonian metacentrics generally possess one-break chromosome rearrangement and the reversible ap- twice the centric pearance and disappearance of telomeres and centromeres. structure of rod chromosomes (7-10). In the Such events are quite discordant with classical cytogenetic grasshopper Neopodismopsis, Moens' (11) electron micrographs theories, which assume all chromosome rearrangements to re- showed this doubled "knob"-like structure to be penetrated by quire at least two breaks and consider centromeres and telo- twice as many microtubules as the single centric knob of rod meres as immutable structures rather than structures deter- chromosomes. Thus, a metacentric's centric region often ap- mined by mutable DNA sequences. Cytogenetic data from pears doubled and capable of splitting by fission, each half spontaneous and induced telomere-telomere fusions in mam- mals sup ort a molecular model of terminal DNA synthesis in becoming a functional centromere (8, 10). which all ttelomeres are similar and recombine before replica- Robertsonian rearrangements, especially the fissions, reveal tion and subsequent separation. This, along with evidence for the inadequacy of Muller's rules, especially his concept of a hypothetical DNA sequence, the kinetochore organizer, centromeres and telomeres as immutable structures (1), and readily explains latent telomeres, latent centromeres, and re- imply some or all of the following: (i) dicentrics can be stable; versible (one-break) Robertsonian rearrangements.
    [Show full text]
  • Pericentromeric Satellite Repeat Expansions Through RNA-Derived DNA Intermediates in Cancer
    Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer Francesca Bersania, Eunjung Leeb,c, Peter V. Kharchenkob,d, Andrew W. Xub, Mingzhu Liua,e, Kristina Xegaa, Olivia C. MacKenziea, Brian W. Brannigana, Ben S. Wittnera, Hyunchul Jungf, Sridhar Ramaswamya,g, Peter J. Parkb,c,h, Shyamala Maheswarana,i, David T. Tinga,g,1,2, and Daniel A. Habera,e,g,1,2 aMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129; bCenter for Biomedical Informatics, Harvard Medical School, Boston, MA 02115; cDivision of Genetics, Brigham and Women’s Hospital, Boston, MA 02115; dHematology/Oncology Program, Children’s Hospital, Boston, MA 02115; eHoward Hughes Medical Institute, Chevy Chase, MD 20815; fSamsung Medical Center, Seoul 135-710, Korea; gDepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114; hInformatics Program, Children’s Hospital, Boston, MA 02115; and iDepartment of Surgery, Massachusetts General Hospital, Boston, MA 02114 Edited by Carol Prives, Columbia University, New York, NY, and approved October 5, 2015 (received for review September 11, 2015) Aberrant transcription of the pericentromeric human satellite II In establishing models to study the molecular basis of HSATII (HSATII) repeat is present in a wide variety of epithelial cancers. In RNA overexpression in cancer, we found that growth of cells deriving experimental systems to study its deregulation, we under nonadherent conditions is sufficient to trigger induction of observed that HSATII expression is induced in colon cancer cells this satellite repeat. Unexpectedly, under these and other condi- cultured as xenografts or under nonadherent conditions in vitro, but tions, we uncovered that these repeated transcripts are reverse- it is rapidly lost in standard 2D cultures.
    [Show full text]
  • Identification and Characterization of Satellite Dnas in Two-Toed Sloths Of
    www.nature.com/scientificreports OPEN Identifcation and characterization of satellite DNAs in two‑toed sloths of the genus Choloepus (Megalonychidae, Xenarthra) Radarane Santos Sena1, Pedro Heringer1, Mirela Pelizaro Valeri1, Valéria Socorro Pereira2, Gustavo C. S. Kuhn1 & Marta Svartman1* Choloepus, the only extant genus of the Megalonychidae family, is composed of two living species of two‑toed sloths: Choloepus didactylus and C. hofmanni. In this work, we identifed and characterized the main satellite DNAs (satDNAs) in the sequenced genomes of these two species. SATCHO1, the most abundant satDNA in both species, is composed of 117 bp tandem repeat sequences. The second most abundant satDNA, SATCHO2, is composed of ~ 2292 bp tandem repeats. Fluorescence in situ hybridization in C. hofmanni revealed that both satDNAs are located in the centromeric regions of all chromosomes, except the X. In fact, these satDNAs present some centromeric characteristics in their sequences, such as dyad symmetries predicted to form secondary structures. PCR experiments indicated the presence of SATCHO1 sequences in two other Xenarthra species: the tree‑toed sloth Bradypus variegatus and the anteater Myrmecophaga tridactyla. Nevertheless, SATCHO1 is present as large tandem arrays only in Choloepus species, thus likely representing a satDNA exclusively in this genus. Our results reveal interesting features of the satDNA landscape in Choloepus species with the potential to aid future phylogenetic studies in Xenarthra and mammalian genomes in general. A signifcant part of eukaryotic genomes, ~ 30% in some plants to more than 50% in some insects and mammals, is composed of tandemly organized highly repetitive sequences, known as satellite DNAs (satDNAs) (reviewed in Ref.1).
    [Show full text]