DOCSLIB.ORG

Sequence Evolution of the Sperm Ligand Zonadhesin Correlates Negatively with Body Weight Dimorphism in Primates

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Sequence Evolution of the Sperm Ligand Zonadhesin Correlates Negatively with Body Weight Dimorphism in Primates ORIGINAL ARTICLE doi:10.1111/j.1558-5646.2007.00035.x SEQUENCE EVOLUTION OF THE SPERM LIGAND ZONADHESIN CORRELATES NEGATIVELY WITH BODY WEIGHT DIMORPHISM IN PRIMATES Holger Herlyn1,2 and Hans Zischler1,3 1Institute of Anthropology, University of Mainz, Colonel-Kleinmann-Weg 2 (SB II), D-55099, Germany 2E-mail: [email protected] 3E-mail: [email protected] Received August 24, 2006 Accepted October 9, 2006 Sexual selection has repeatedly been shown to be the probable driving force behind the positive Darwinian evolution of genes affecting male reproductive success. Here we compare the sequence evolution of the sperm ligand zonadhesin with body mass di- morphism in primates. In contrast to previous related studies, the present approach takes into account not only catarrhine primates, but also platyrrhines and lemurs. In detail, we analyze the sequence evolution of concatenated zonadhesin fragments (555 bp) of four Lemuroidea, five Platyrrhini, and seven Catarrhini, using the rate ratio of nonsynonymous to synonymous substitutions (dn/ds = ␻). Unexpectedly, subsequent regression analyzes between ␻ estimates for the terminal branches of a primate phy- logeny and residual male body mass reveal that sequence evolution of zonadhesin decreases with increasing sexual dimorphism in body weight. Mapping published mating system classifications onto these results illustrates that unimale breeding species show a tendency for rather slow sequence evolution of zonadhesin and comparably pronounced sexual dimorphism in body weight. Female choice and sperm competition can be assumed to drive the evolution of zonadhesin. We speculate that the level of sperm competition is lower in more sexually dimorphic primates because males of these species monopolize access to fertile females more successfully. Thus, variation in sperm competition may be driving the observed negative correlation of sequence evolution and sexual dimorphism in body weight. KEY WORDS: Breeding system, female choice, mating system, sexual dimorphism, sperm competition, sperm–egg interaction, zonadhesin. With the increasing amounts of comparative sequence data, evi- tion of genes that influence the reproductive success of males. In- dence is growing that positive selection plays a crucial role in the creased levels of sexual selection should thus accelerate sequence evolution of genes involved in mating behavior, fertilization, sper- evolution of genes affecting male reproductive success. The first matogenesis, and sex determination (reviewed in Swanson and suggestion of such a relationship came from comparative analysis Vacquier 2002). As it affects the evolution of physical traits such of the protamine gene cluster in primates (Wyckoff et al. 2000; as testis size, sperm morphology, and baculum length (Harcourt see also Rooney and Zhang 1999). Subsequently, Dorus et al. et al. 1981; Anderson and Dixson 2002; for review see Dixson (2004) reported a positive correlation of sequence evolution of and Anderson 2004), sexual selection may also drive the evolu- semenogelin 2, a main component of copulatory plugs, and the C 2007 The Author(s) 289 Journal compilation C 2007 The Society for the Study of Evolution H. HERLYN AND H. ZISCHLER level of sperm competition, a form of sexual selection. However, ability (for a compilation of body mass data in primates see, e.g., the estimates of sperm competition used by Dorus et al. (2004), Kappeler 1991, Lindenfors 2002). Initially, a combination of hap- that is, the number of peri-ovulatory partners and residual testis lorhine and strepsirhine data in one statistical approach might size are not available for most primate species. Moreover, ex- appear problematical because body mass dimorphism is much cept for one platyrrhine monkey serving as outgroup (Dorus et al. less common in strepsirhines than in haplorhines (Kappeler 1991, 2004), previous studies were confined to Hominoidea (Wyckoff 1997; Lindenfors and Tullberg 1998; Plavcan 2001; Lindenfors et al. 2000) and Catarrhini (Dorus et al. 2004). Yet seasonality of 2002). However, in the context of the present study the compared breeding (Rowe 1996) suggest high levels of sexual selection in species do not have to be sexually dimorphic. Instead, the sexes Lemuroidea. Finally, sexual selection may be primarily behavioral may be of similar or equal size, and females may even be larger in many species, and successful males may prevent access to re- than males. The only prerequisite is that the sample covers vari- ceptive females. Such behavior could thus reduce the opportunity ance of dimorphism within primates. Another concern could be for interindividual sperm competition. that body mass is under the influence of different selective pres- sures and constraints. Though this is certainly the case, recent ZONADHESIN studies have shown a strong correlation between body mass di- Based on a broad primate sampling, including Platyrrhini and morphism and other indirect measures of sperm competition, such Lemuroidea, we investigate possible correlations between the se- as operational sex ratio, mating systems, and male–male compe- quence evolution of the sperm ligand zonadhesin and sexual se- tition levels (Mitani et al. 1996; Plavcan 2001, 2004; Lindenfors lection of males. Pseudogenization of zonadhesin might occur 2002; Lindenfors et al. 2004). Therefore, we consider sexual di- sporadically (see Hillier et al. 2003). However, we found no evi- morphism in body mass as another surrogate measure of sexual dence for such a process in previous studies (Herlyn and Zischler selection. 2005a,b) and, thus, consider zonadhesin a suitable subject for evolutionary studies. The ∼62 kb of the human zonadhesin locus stretch over 48 exons coding for the 2811 amino acids of precur- Materials and Methods sor zonadhesin (see ENSEMBL Gene: ENSG00000146839). In PCR, SEQUENCING, AND ALIGNING primates, Sus scrofa, and Oryctolagus cuniculus, precursor zon- As it is very difficult to obtain zonadhesin expressing tissue such adhesin encodes for two MAM (meprin/A5 antigen/mu receptor as testis, new sequences were generated on the basis of genomic tyrosine phosphatase) domains, a mucin-like tandem repeat, and DNA rather than cDNA. Given the extensive intronic information five so-called D domains, homologous to von Willebrand factor D covered by the zonadhesin locus (∼53 kb, see ENSEMBL Gene: (Hardy and Garbers 1995; Gao and Garbers 1998; Lea et al. 2001; ENSG00000146839), we confined the present approach to the Herlyn and Zischler 2005a,b). The mucin-like domain of zonad- exonic information upstream and downstream of three exception- hesin consists of tandemly arranged seven amino acid motifs that ally short introns, that is, intron 9–10 (108 bp, taking the human evolve in a concerted fashion. Contrary to this, zonadhesin MAM ortholog as reference), intron 20–21 (110 bp), and intron 32–33 and D domains evolve divergently (Herlyn and Zischler 2006), (93 bp). Exons 9 and 10 encode for fragments of MAM domains apparently driven by positive selection at the level of both single 1 and 2. Exons 20 and 21 and exons 32 and 33 are located within codon sites (Swanson et al. 2003) and posttranslational modifica- domains D1 and D3, respectively. tions (Herlyn and Zischler 2005a,b). The processing of precursor Genomic DNA was extracted from different tissues of the zonadhesin leads to the formation of four subunits that partly bind following primate representatives: Lemuroidea (Eulemur fulvus, to the egg’s zona pellucida (see Hardy and Garbers 1995; Gao and Lemur catta, Microcebus murinus, Varecia variegata), Platyrrhini Garbers 1998; Lea et al. 2001; Bi et al. 2003). (Aotus azarai, Ateles belzebuth, Callicebus cupreus, Saguinus fus- cicollis, Saimiri sciureus), and Cercopithecoidea (Cercopithecus BODY MASS DIMORPHISM mitis, Erythrocebus patas, Macaca mulatta, Mandrillus sphinx, In most primate species, long life spans, low reproductive rates, Papio hamadryas, Pygathrix nemaeus). Primers specific for Cer- and practical difficulties in the field render it impossible to directly copithecoidea, Platyrrhini, and Lemuroidea (Table 1) were de- measure sexual selection on males (Plavcan 2004). Moreover, as signed using published data from GenBank (U40024, AF244982, mentioned above, surrogate measures of sperm competition such AF332975, AY428845-58).Fragments of 310–385 bp length com- as residual testis size and number of peri-ovulatory partners are prising introns 9–10, 20–21, and 32–33, and part of the adjacent not available for most primate species. For both reasons, it is de- exons were amplified by wax-mediated hotstart PCR using the sirable to employ more available estimates when analyzing sexual Taq PCR Core Kit (Qiagen). Each reaction (30 ␮L) contained selection of males on the basis of more comprehensive samplings. 0.5 U Taq polymerase (AmpliTaq, Perkin Elmer), 15 pmol dNTPs, Data on body mass dimorphism fulfil the criterion of easy avail- 10 mM Tris–HCl (pH 8.4), 50 mM KCl, 2 mM MgCl2, 0.1% Triton 290 EVOLUTION FEBRUARY 2007 SEQUENCE EVOLUTION AND SEXUAL DIMORPHISM Table 1. Primers used for amplification of the three analyzed zonadhesin fragments. 1 ◦ Location Taxon Primer-sequence (5 -3 ) T m ( C) Exons 9, cercopithecoidea-1 for CGTGGT(AG)GGCGTTTTTG 54.0 Intron 9-10, rev TGCATTAGGGAAACCTCC 53.7 Exon 10 platyrrhini-1 for TCGTGGTGGG(CT)(AG)TTTTTG 53.7 rev CTG(CT)(CA)CT(AG)GGGAAATCTC 54.8 strepsirhini-1 for1 CGTGGTGGG(CT)(AG)T(ATG)TTTG 53.6 rev1 CTCAAGGTAGATATAGTG 49.1 for2 GGAC(AG)GATACAGTT(CT)ACCGTG 59.8 rev2 TGGAGGGGTACATTT(CT)TATGTC
Load more

Recommended publications
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • Novel Targets of Apparently Idiopathic Male Infertility
    International Journal of Molecular Sciences Review Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility Rossella Cannarella * , Rosita A. Condorelli , Laura M. Mongioì, Sandro La Vignera * and Aldo E. Calogero Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; [email protected] (R.A.C.); [email protected] (L.M.M.); [email protected] (A.E.C.) * Correspondence: [email protected] (R.C.); [email protected] (S.L.V.) Received: 8 February 2020; Accepted: 2 March 2020; Published: 3 March 2020 Abstract: Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm-oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility. Keywords: spermatogenetic failure; embryo growth; male infertility; spermatogenesis; recurrent pregnancy loss; sperm proteome; DNA fragmentation; sperm transcriptome 1. Introduction Infertility is a widespread condition in industrialized countries, affecting up to 15% of couples of childbearing age [1]. It is defined as the inability to achieve conception after 1–2 years of unprotected sexual intercourse [2].
    [Show full text]
  • Transcriptome Analysis for Novel Peptide in Breeding Gland of Hymenochirus Boettgeri Minjin Ko University of the Pacific, M [email protected]
    University of the Pacific Scholarly Commons University of the Pacific Theses and Dissertations Graduate School 2019 Transcriptome analysis for novel peptide in breeding gland of Hymenochirus boettgeri Minjin Ko University of the Pacific, [email protected] Follow this and additional works at: https://scholarlycommons.pacific.edu/uop_etds Part of the Biology Commons Recommended Citation Ko, Minjin. (2019). Transcriptome analysis for novel peptide in breeding gland of Hymenochirus boettgeri. University of the Pacific, Thesis. https://scholarlycommons.pacific.edu/uop_etds/3615 This Thesis is brought to you for free and open access by the Graduate School at Scholarly Commons. It has been accepted for inclusion in University of the Pacific Theses and Dissertations by an authorized administrator of Scholarly Commons. For more information, please contact [email protected]. 1 TRANSCRIPTOME ANALYSIS FOR NOVEL PEPTIDES IN BREEDING GLAND OF HYMENOCHIRUS BOETTGERI By Minjin Ko A Thesis Submitted to the Graduate School In Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE College of the Pacific Biological Sciences University of the Pacific Stockton, California 2019 2 TRANSCRIPTOME ANALYSIS FOR NOVEL PEPTIDES IN BREEDING GLAND OF HYMENOCHIRUS BOETTGERI By Minjin Ko APPROVED BY: Dissertation Advisor: Eric Thomas, Ph.D. Committee Member: Jane Khudyakov, Ph.D. Committee Member: Doug Risser, Ph.D. Committee Member: Ajna Rivera, Ph.D. Department Co-Chairs: Lisa Wrischnik, Ph.D. and Eric Thomas, Ph.D. Dean of the Graduate School: Thomas Naehr, Ph.D. 3 DEDICATION I dedicate this to my parents. 4 Transcriptome Analysis for Novel Peptides in Breeding Gland of Hymenochirus Boettgeri Abstract By Minjin Ko University of the Pacific 2019 The primary goal of the project was to find nucleotide sequences potentially encoding a pheromone from the breeding gland of Hymenochirus boettgeri .
    [Show full text]
  • Reproductive Protein Evolution Within and Between Species: Maintenance of Divergent ZP3 Alleles in Peromyscus
    Molecular Ecology (2008) 17, 2616–2628 doi: 10.1111/j.1365-294X.2008.03780.x ReproductiveBlackwell Publishing Ltd protein evolution within and between species: maintenance of divergent ZP3 alleles in Peromyscus LESLIE M. TURNER*† and HOPI E. HOEKSTRA† *Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093, USA, †Department of Organismic and Evolutionary Biology and The Museum of Comparative Zoology, Harvard University, Cambridge, MA 02138, USA Abstract In a variety of animal taxa, proteins involved in reproduction evolve more rapidly than non- reproductive proteins. Most studies of reproductive protein evolution, however, focus on divergence between species, and little is known about differentiation among populations within a species. Here we investigate the molecular population genetics of the protein ZP3 within two Peromyscus species. ZP3 is an egg coat protein involved in primary binding of egg and sperm and is essential for fertilization. We find that amino acid polymorphism in the sperm-combining region of ZP3 is high relative to silent polymorphism in both species of Peromyscus. In addition, while there is geographical structure at a mitochondrial gene (Cytb), a nuclear gene (Lcat) and eight microsatellite loci, we find no evidence for geographical structure at Zp3 in Peromyscus truei. These patterns are consistent with the maintenance of ZP3 alleles by balancing selection, possibly due to sexual conflict or pathogen resistance. However, we do not find evidence that reinforcement promotes ZP3 diversification; allelic variation in P. truei is similar among populations, including populations allopatric and sympatric with sibling species. In fact, most alleles are present in all populations sampled across P.
    [Show full text]
  • Supplementary Table 1. Control System M1 and M2 Significantly Expressed Genes Involved in Macrophage Differentiation and Polarization
    Supplementary Table 1. Control system M1 and M2 significantly expressed genes involved in macrophage differentiation and polarization. M1 Gene Name Entrez M2 Gene Name Entrez Gene ID Gene ID Interferon, gamma-inducible protein 16 3428 Cystinosis, nephropathic 1497 Hypothetical protein BC012330 116071 Protease, serine, 22 64063 Chemokine (C-C motif) ligand 2 6347 Niemann-Pick disease, type C1 4864 Poly (ADP-ribose) polymerase family, 83666 Phosphatidylinositol binding clathrin assembly 8301 member 9 protein Lipocalin-interacting membrane receptor 55716 Solute carrier family 38, member 6 145389 Epithelial stromal interaction 1 (breast) 94240 Homeobox C14 360030 2'-5'-oligoadenylate synthetase 3, 4940 Selenoprotein T 51714 100kDa Somatostatin receptor 2 6752 Angiopoietin-like 4 51129 Chemokine (C-X-C motif) ligand 16 58191 GRP1 (general receptor for phosphoinositides 160622 1)-associated scaffold protein GTPase, IMAP family member 8 155038 Nuclear receptor subfamily 4, group A, 8013 member 3 DR1-associated protein 1 (negative 10589 Chromosome 21 open reading frame 82 114036 cofactor 2 alpha) Interferon-induced protein 44 10964 Oviductal glycoprotein 1, 120kDa (mucin 9, 5016 oviductin) PTK2B protein tyrosine kinase 2 beta 2185 Chromosome 9 open reading frame 150 286343 Hypothetical protein BC012317 93082 30 kDa protein 55831 N-acetylglucosamine kinase 55577 Growth arrest-specific 2 like 3 283431 TPR domain containing STI2 199223 Serine protease inhibitor, Kunitz type 1 6692 Phosphodiesterase 4D interacting 9659 FK506 binding protein 1A, 12kDa
    [Show full text]
  • Zonadhesin-Like Genes in Three Fish Species: Atlantic Salmon (Salmo Salar), Puffer Fish (Tahyugu Rubripes) and Zebrafish (Danio Rerio)
    Zonadhesin-like genes in three fish species: Atlantic salmon (Salmo salar), Puffer fish (Tahyugu rubripes) and Zebrafish (Danio rerio) Peter Nicholas Darien Hunt B. Sc., University of Victoria, 2002 A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE In the Department of Biology We accept this thesis as conforming to the standard required. O Peter Nicholas Darien Hunt, 2004 University of Victoria All rights reserved. This thesis may not be reproduced in whole or in part, by photocopying or other means, without permission of the author. Supervisor: Dr. Ben F. Koop Abstract The sperm membrane protein zonadhesin (ZAN) has been characterized in mammals and has been implicated in species-specific egg-sperm binding interactions. Zonadhesin is the only protein that contains MAM, mucin and von Willebrand D domains. A zonadhesin-like transcript was obtained fi-om an Atlantic salmon gut tissue cDNA library. This transcript and the corresponding genomic locus were sequenced. A zonadhesin-like gene (ZLG) with a predicted open reading fi-ame of 4,5 18 nucleotides that encodes MAM, mucin and VWD domains was characterized. Although the predicted protein contains the same major domains as zonadhesin, the domain order is altered. ZLG is expressed in the liver and the gut but not in the testis as a typical zonadhesin. This gene is unlikely to be directly involved in reproduction, because it has a unique domain structure and expression, but is likely to have a novel function. In contrast, zonadhesin-like genes with the same domain content and order as mammalian zonadhesins can be deduced from puffer fish and zebrafish genomic sequencing projects.
    [Show full text]
  • Deciphering the Genetic Basis of Spanish Familial Testicular Cancer
    Departamento de Bioquímica Deciphering the genetic basis of Spanish familial testicular cancer Tesis doctoral Beatriz Paumard Hernández Madrid, 2017 Departamento de Bioquímica Facultad de Medicina Universidad Autónoma de Madrid Deciphering the genetic basis of Spanish familial testicular cancer Tesis doctoral presentada por: Beatriz Paumard Hernández Licenciada en Biología por la Universidad Autónoma de Madrid (UAM) Director de la Tesis: Dr. Javier Benítez Director del Programa de Genética del Cáncer Humano (CNIO) Jefe del Grupo de Genética Humana (CNIO) Grupo de Genética Humana Programa de Genética del Cáncer Humano Centro Nacional de Investigaciones Oncológicas (CNIO) Dr. Javier Benítez Ortiz, Director del grupo de Genética del Cáncer Humano del Centro Nacional de Investigaciones Oncológicas (CNIO) CERTIFICA: Que Doña Beatriz Paumard Hernández, Licenciada en Biología por la Universidad Autónoma de Madrid, ha realizado la presente Tesis Doctoral “Deciphering the genec basis of Spanish familial testicular cáncer” y que a su juicio reúne plenamente todos los requisitos necesarios para optar al Grado de Doctor en Bioquímica, Biología Molecular, Biomedicina y Biotecnología, a cuyos efectos será presentada en la Universidad Autónoma de Madrid. El trabajo ha sido realizado bajo mi dirección, autorizando su presentación ante el Tribunal calificador. Y para que así conste, se extiende el presente certificado, Madrid, Junio 2017 Fdo: Director de la Tesis Fdo: Tutor de la Tesis VoBo del Director Dr.Javier Benítez Ortiz La presente Tesis Doctoral se realizó en el Grupo de Genética Humana en el Centro Nacional de Investigaciones Oncológicas (CNIO) de Madrid durante los años 2013 y 2017 bajo la supervisión del Dr. Javier Benítez Las siguientes becas, ayudas y proyectos han permitido la realización de esta Tesis Doctoral: “La Caixa”- Severo Ochoa International Phd Programmme at CNIO Proyecto FIS PI12/0070 BRIDGES Project (H2020) Summary / Resumen SUMMARY Testicular cancer is a frequently occurring disease among adult males, and it accounts for 1-2% of all male tumors.
    [Show full text]
  • Comprehensive Genomic Characterization of Mantle Cell Lymphoma
    Comprehensive Genomic Characterization of Mantle Cell Lymphoma by Arezoo Mohajeri M.Sc., Lund University, 2012 B.Sc., Shiraz University, 2007 Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in the Department of Molecular Biology and Biochemistry Faculty of Science © Arezoo Mohajeri SIMON FRASER UNIVERSITY Summer 2017 Copyright in this work rests with the author. Please ensure that any reproduction or re-use is done in accordance with the relevant national copyright legislation. Approval Name: Arezoo Mohajeri Degree: Master of Science Title: Comprehensive Genomic Characterization of Mantle Cell Lymphoma Examining Committee: Chair: Dr. Nancy Forde Associate Professor Department of Physics Dr. Mark Paetzel Senior Supervisor Professor Dr. Sharon Gorski Supervisor Professor Dr. Christian Steidl Supervisor Associate Professor Department of Pathology University of British Columbia Dr. Jack Chen Internal Examiner Professor Date Defended/Approved: June 29, 2017 Ethics Statement ii Abstract Mantle cell lymphoma (MCL) is a rare, aggressive and incurable type of cancer with a high incidence of systemic dissemination and poor survival outcomes. Understanding the genetics and biology of MCL is necessary for development of suitable biomarkers and therapies. A limited number of sequencing-based studies were performed on MCL recently, which improved the knowledge on causal mutations and molecular mechanisms of MCL. However, because of the small cohort sizes of these studies and use of outdated computational tools and databases have limited the findings of these studies. The objective of our study was to identify the genetic alterations and molecular pathways that are associated with the development, progression, and dissemination of MCL by using leading-edge bioinformatics tools, up-to-date molecular biology databases, and a large sample size.
    [Show full text]
  • Whole Exome Sequencing in Adult-Onset Hearing Loss Reveals A
    Lewis et al. BMC Medical Genomics (2018) 11:77 https://doi.org/10.1186/s12920-018-0395-1 RESEARCHARTICLE Open Access Whole exome sequencing in adult-onset hearing loss reveals a high load of predicted pathogenic variants in known deafness-associated genes and identifies new candidate genes Morag A. Lewis1,2, Lisa S. Nolan3, Barbara A. Cadge3, Lois J. Matthews4, Bradley A. Schulte4, Judy R. Dubno4, Karen P. Steel1,2† and Sally J. Dawson3*† Abstract Background: Deafness is a highly heterogenous disorder with over 100 genes known to underlie human non- syndromic hearing impairment. However, many more remain undiscovered, particularly those involved in the most common form of deafness: adult-onset progressive hearing loss. Despite several genome-wide association studies of adult hearing status, it remains unclear whether the genetic architecture of this common sensory loss consists of multiple rare variants each with large effect size or many common susceptibility variants each with small to medium effects. As next generation sequencing is now being utilised in clinical diagnosis, our aim was to explore the viability of diagnosing the genetic cause of hearing loss using whole exome sequencing in individual subjects as in a clinical setting. Methods: We performed exome sequencing of thirty patients selected for distinct phenotypic sub-types from well- characterised cohorts of 1479 people with adult-onset hearing loss. Results: Every individual carried predicted pathogenic variants in at least ten deafness-associated genes; similar findings were obtained from an analysis of the 1000 Genomes Project data unselected for hearing status. We have identified putative causal variants in known deafness genes and several novel candidate genes, including NEDD4 and NEFH that were mutated in multiple individuals.
    [Show full text]
  • Comparative Analysis of the Gene-Dense ACHE/TFR2 Region on Human Chromosome 7Q22 with the Orthologous Region on Mouse Chromosome 5 Michael D
    1352–1365 Nucleic Acids Research, 2001, Vol. 29, No. 6 © 2001 Oxford University Press Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5 Michael D. Wilson, Cathy Riemer1, Duane W. Martindale, Pamela Schnupf, Andrew P. Boright2, Tony L. Cheung3,DanielM.Hardy3, Scott Schwartz1,StephenW.Scherer2,Lap-CheeTsui2, Webb Miller1 and Ben F. Koop* Department of Biology, Centre for Environmental Health, PO Box 3020, University of Victoria, Victoria, British Columbia V8W 3N5, Canada, 1Department of Computer Science and Engineering, Pennsylvania State University, University Park, PA 16802, USA, 2Department of Genetics, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada and 3Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 Fourth Street, Lubbock, TX 79430, USA Received October 13, 2000; Revised and Accepted January 26, 2001 DDBJ/EMBL/GenBank accession nos AF312032, AF312033 ABSTRACT can be viewed at http://web.uvic.ca/~bioweb/laj.html. Chromosome 7q22 has been the focus of many cyto- Laj is available at http://bio.cse.psu.edu/, along with online documentation and additional examples of genetic and molecular studies aimed at delineating annotated genomic regions. regions commonly deleted in myeloid leukemias and myelodysplastic syndromes. We have compared a gene-dense, GC-rich sub-region of 7q22 with the INTRODUCTION orthologous region on mouse chromosome 5. A The Giemsa negative band q22 of human chromosome 7 is an physical map of 640 kb of genomic DNA from mouse area known to be gene-rich and prone to chromosomal chromosome 5 was derived from a series of over- breakage.
    [Show full text]
  • Construction of a Catalogue of Amphioxus (Branchiostoma Floridae
    Construction of a catalogue of amphioxus (Branchiostoma Jîoridae) genes expressed at neurula and gastrula stages by oligonucleotide fingerprinting. Georgia Panopoulou a thesis submitted for the degree of Doctor of Philosophy in the University of London Windeyer Institute of Medical Sciences Department of Molecular Pathology and Clinical Biochemistry University College London Windeyer Building 46 Cleveland Street London W IP 6DB ENGLAND Max-Planck Institute fuer Molekulare Genetik Department Prof. Hans Lehrach Ihnestrasse 73 D-14195 Berlin GERMANY June 1999 ProQuest Number: U643583 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U643583 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 To Dimitri, Vicky and Lena Abstract So far 9% of the human genome has been sequenced and for more than 50% of human genes there is a representative tag sequence (61,811 Unigene clusters, NCBI release statistics 1999). The major challenge of the next phase of the human genome project will be to try to understand the function of those genes. Cross-species comparison is an effective tool for providing clues based on sequence conservation combined with the possibility of genetic manipulations such as generation of mutants or crosses.
    [Show full text]
  • Download Special Issue
    BioMed Research International Advances in Computational Genomics NeuralGuest Editors: Computation Leng Han, Yan Guo, Zhixi Su, for Siyuan Rehabilitation Zheng, and Zhixiang Lu Advances in Computational Genomics BioMed Research International Advances in Computational Genomics Guest Editors: Leng Han, Yan Guo, Zhixi Su, Siyuan Zheng, and Zhixiang Lu Copyright © 2015 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “BioMed Research International.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Contents Advances in Computational Genomics, Leng Han, Yan Guo, Zhixi Su, Siyuan Zheng, and Zhixiang Lu Volume 2015, Article ID 187803, 2 pages Genepleio Software for Effective Estimation of Gene Pleiotropy from Protein Sequences, Wenhai Chen, Dandan Chen, Ming Zhao, Yangyun Zou, Yanwu Zeng, and Xun Gu Volume 2015, Article ID 269150, 6 pages Integration Strategy Is a Key Step in Network-Based Analysis and Dramatically Affects Network Topological Properties and Inferring Outcomes, Nana Jin, Deng Wu, Yonghui Gong, Xiaoman Bi, Hong Jiang, Kongning Li, and Qianghu Wang Volume 2014, Article ID 296349, 13 pages Informative Gene Selection and Direct Classification of Tumor Based on Chi-Square Test of Pairwise Gene Interactions, Hongyan Zhang, Lanzhi Li, Chao Luo, Congwei Sun, Yuan Chen, Zhijun Dai, and Zheming Yuan Volume 2014, Article ID 589290,
    [Show full text]