WWOX (WW domain-containing oxidoreductase) is the gene mapping at FRA16D HSA16q23.1, the second most active common fragile site in the human genome. In this study we characterized at a detailed molecular level WWOX in the bovine genome. First, we sequenced cDNA from various tissues and obtained evidence in support of a 9-exon structure for the gene, similar to the human gene. Then, we recovered BACs using exon tags and annotated the gene to a >1-Mb genomic region of BTA18 using the Btau 4.0 genome assembly as a reference, thus resolving an issue related to exon 9, which is not included in the genomic annotation of the gene in the Entrez database. Finally, BACs spanning WWOX were used as FISH probes to obtain comparative mapping of the gene in Bos taurus, Bubalus bubalis, Ovis aries and Capra hircus to BTA18q12.1, BBU18q13, OAR14q12.1 and CHI18q12.1, respectively. Our data show that the chromosomal location of WWOX is conserved between man and 4 major domesticated species. Moreover, the annotation of the bovine gene also suggests a highly conserved genomic arrangement, including number and size of introns.

Keywords:
BACs, Bovine, Comparative mapping, FISH, Gene annotation, WWOX
1.
Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM: WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3–24.1, a region frequently affected in breast cancer. Cancer Res 60:2140–2145 (2000).
2.
Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101:2999–3004 (2004).
3.
Cribiu EP, Di Berardino D, Di Meo GP, Eggen A, Gallagher DS, et al: International System for Chromosome Nomenclature of Domestic Bovids (ISCNDB 2000). Cytogenet Cell Genet 92:283–299 (2001).
4.
Di Meo GP, Perucatti A, Uboldi C, Roperto S, Incarnato D, et al: Comparative mapping of the fragile histidine triad (FHIT) gene in cattle, river buffalo, sheep and goat by FISH and assignment to BTA22 by RH-mapping: a comparison with HSA3. Anim Genet 36:363–364 (2005).
5.
Di Meo GP, Perucatti A, Floriot S, Hayes H, Schibler L, et al: An advanced sheep (Ovis aries, 2n = 54) cytogenetic map and assignment of 88 new loci by fluorescent in situ hybridization and R-banding. Anim Genet 38:233–240 (2007).
6.
Di Meo GP, Perucatti A, Floriot S, Hayes H, Schibler L, et al: An extended river buffalo (Bubalus bubalus, 2n = 50) cytogenetic map: assignment of 68 autosomal loci by FISH-mapping and R-banding and comparison with human chromosomes. Chromosome Res 16:827–837 (2008).
7.
Durkin SG, Glover TW: Chromosome fragile sites. Annu Rev Genet 41:169–192 (2007).
8.
Eggen A, Gautier M, Billaut A, Petit E, Hayes H, et al: Construction and characterization of a bovine BAC library with four genome-equivalent coverage. Genet Sel Evol 33:543–548 (2001).
9.
Guidi E, Uboldi C, Ferretti L: Molecular analysis of the fragile histidine triad (FHIT) tumor suppressor gene in vesical tumors of cattle with chronic enzootic hematuria (CEH). Cytogenet Genome Res 120:173–177 (2008).
10.
Hayes H: Chromosome painting with human chromosome-specific DNA libraries reveals the extent and distribution of conserved segments in bovine chromosomes. Cytogenet Cell Genet 71:168–174 (1995).
11.
Hecht F, Glover TW: Cancer chromosome breakpoints and common fragile sites induced by aphidicolin. Cancer Genet Cytogenet 13:185–188 (1984).
12.
Iannuzzi L: Standard karyotype of river buffalo (Bubalus bubalis L., 2n = 50). Report of the committee for the standardization of banded karyotypes of the river buffalo. Cytogenet Cell Genet 67:102–113 (1994).
13.
Iannuzzi L, Di Berardino D: Tools of the trade: diagnostic and research applied to domestic animal cytogenetics. J Appl Genet 49:357–366 (2008).
14.
Iannuzzi L, Di Meo GP, Perucatti A, Bardaro T: ZOO-FISH and R-banding reveal extensive conservation of human chromosome regions in euchromatic regions of river buffalo chromosomes. Cytogenet Cell Genet 82:210–214 (1998).
15.
Iannuzzi L, Di Meo GP, Perucatti A, Incarnato D: Comparison of the human with the sheep genomes by use of human chromosome-specific painting probes. Mammal Genome 10:719–723 (1999).
16.
Iliopoulos D, Guler G, Han SY, Druck T, Ottey M, et al: Roles of FHIT and WWOX fragile genes in cancer. Cancer Lett 232:27–36 (2006).
17.
Lee SH, Kim WH, Kim HK, Woo KM, Nam HS, et al: Altered expression of the fragile histidine triad gene in primary gastric adenocarcinomas. Biochem Biophys Res Commun 284:850–855 (2001).
18.
Matsuyama A, Shiraishi T, Trapasso F, Kuroki T, Alder H, et al: Fragile site orthologs FHIT/FRA3B and Fhit/Fra14a2: evolutionarily conserved but highly recombinogenic. Proc Natl Acad Sci USA 100:14988–14993 (2003).
19.
Murphy WJ, Larkin DM, Everts-van der Wind A, Bourque G, Tesler G, et al: Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps. Science 309:613–617 (2005).
20.
Nicodemo D, Coppola G, Pauciullo A, Cosenza G, Ramunno L, et al: Chromosomal expression and localization of aphidicolin-induced fragile sites in the standard karyotype of river buffalo (Bubalus bubalis). Cytogenet Genome Res 120:178–182 (2008).
21.
Ohta M, Inoue H, Cotticelli MG, Kastury K, Baffa R, et al: The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell 84:587–597 (1996).
22.
Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, et al: WWOX: a candidate tumor suppressor gene involved in multiple tumor types. Proc Natl Acad Sci USA 98:11417–11422 (2001).
23.
Panagopoulos I, Thelin S, Mertens F, Mitelman F, Aman P: Variable FHIT transcripts in non-neoplastic tissues. Genes Chromosomes Cancer 19:215–219 (1997).
24.
Robinson TJ, Ruiz-Herrera A, Froenicke L: Dissecting the mammalian genome – new insights into chromosomal evolution. Trends Genet 22:297–301 (2006).
25.
Rodriguez V, Llambí S, Postiglioni A, Guevara K, Rincón G, et al: Localisation of aphidicolin-induced break points in Holstein-Friesian cattle (Bos taurus) using RBG-banding. Genet Sel Evol 34:649–656 (2002).
26.
Ruiz-Herrera A, Castresana J, Robinson TJ: Is mammalian chromosomal evolution driven by regions of genome fragility? Genome Biol 7:R115 (2006).
27.
Sutherland GR: Heritable fragile sites on human chromosomes II. Distribution, phenotypic effects, and cytogenetics. Am J Hum Genet 31:136–48 (1979).
28.
Uboldi C, Guidi E, Roperto S, Russo V, Roperto F, et al: Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT) tumour suppressor gene: characterization of a 2-Mb BAC contig covering the locus, complete annotation of the gene, analysis of cDNA and of physiological expression profiles. BMC Genomics 7:123 (2006).
29.
Yunis JJ, Soreng AL: Constitutive fragile sites and cancer. Science 226:1199–1204 (1984).
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.