Use of Synteny Conversion in Identification of Candidate Genes for Somitogenesis in Humans

DOI: 10.4236/ojo.2012.22013   PDF   HTML   XML   4,985 Downloads   7,224 Views   Citations

Abstract

Understanding the genetic component of scoliosis in humans has relied on the assumption that spine development is conserved across species. Since evolutionary conserved genes tend to lie within synteny blocks (HSBs) and genes which are not conserved lie within evolutionary breakpoint regions (EBRs), HSB analysis may be used to determine if spine development is conserved across species. We hypothesized that vertebral patterning genes are conserved in amniotes and their location is within stable or “syntenic” regions of chromosomes. Seventy seven patterning genes involved in Fgf, Wnt and Notch signaling pathways were analyzed to determine their location within HSBs or EBRs in the genomes of several amniotic species. The human genome was divided into 1 Mbp intervals and a comparison was made to determine whether these genes were preferentially localized within HSBs or EBRs associated with rapid evolution. The results indicate that genes associated with somite development in humans are preferentially located away from the EBRs: 0.014 genes in EBRs on genome average vs. 0.030 on average in other parts of the genome (p-value = 0.01). The concentration of vertebral patterning genes in HSBs, provides evidence that developmental pathways involved in vertebral morphogenesis are likely conserved across amniotes, consistent with their known function. These data support prior observations indicating that gene networks associated with major developmental processes such as neuronal, central nervous system, bone and blood vessel development, some mediated by Wnt and Notch signaling pathways, were less likely to be localized at EBRs.

Share and Cite:

P. Giampietro, C. Raggio and R. Blank, "Use of Synteny Conversion in Identification of Candidate Genes for Somitogenesis in Humans," Open Journal of Orthopedics, Vol. 2 No. 2, 2012, pp. 62-68. doi: 10.4236/ojo.2012.22013.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Scoliosis Research Society, “Glossary of Scoliosis Terms,” Spine, Vol. 1, No. 1, 1976, pp. 57-58. doi:10.1097/00007632-197603000-00008
[2] S. B. Purkiss, B. Driscoll, W. G. Cole and B. Alman, “Idi-opathic Scoliosis in Families of Children with Congenital Scoliosis,” Clinical Orthopaedics and Related Research, Vol. 401, 2002, pp. 27-31. doi:10.1097/00003086-200208000-00005
[3] M. De-queant, E. Glynn, K. Gaundenz, M. Wahl, J. Chen, A. Mushegian and O. Pourquie, “A Complex Oscillating Network of Signaling Genes Underlies the Mouse Segmentation Clock,” Science, Vol. 314, No. 5805, 2006, pp. 1595-1598. doi:10.1126/science.1133141
[4] N. Ghe-branious, R. Blank, C. Raggio, J. Staubli, E. McPherson, L. Ivacic, K. Rasmussen, F. Jacobsen, T.Faciszewski, J. K. Burmester, R. M. Pauli, O. Boachie-Adjei, I. Glurich and P. F. Giampietro, “A Missense T(Brachyury) Mutation Contributes to Vertebral Malformations,” Journal of Bone and Mineral Research, Vol. 23, No. 10 2008, pp. 1576-1583. doi:10.1359/jbmr.080503
[5] N. Ghebranious, J. Burmester, I. Glurich, E. McPherson, L. Ivacic, J. Kislow, K. Rasmussen, V. Kumar, C. Raggio, R. Blank, F. S. Jacobsen, T. Faciszewski, J. Womack and P. F. Giampietro, “Evaluation of SLC35A3 as a Candidate Gene for Human Vertebral Malformations,” American Journal of Medical Genetics, Vol. 140A, No. 12, 2006, pp. 1346-1348. doi:10.1002/ajmg.a.31307
[6] N. Ghebranious, C. L. Raggio, R. D. Blank, E. McPherson, J. K. Burmester, L. Ivacic, K. Rasmussen, J. Kislow, I. Glurich, F. S. Jacobsen, T. Faciszewski, R. M. Pauli, O. Boachie-Adjei and P. F. Giampietro, “Lack of Evidence of WNT3A as a Candidate Gene for Congenital Vertebral Malformations,” Sco-liosis, Vol. 2, 2007, p. 13. doi:10.1186/1748-7161-2-13
[7] P. Giampietro, C. Raggio, C. Reynolds, N. Ghebranious, J. Burmester, I. Glurich, K. Rasmussen, E. McPherson, R. Pauli, S. K. Shukla, S. Merchant, F. S. Jacobsen, T. Faciszewski and R. D. Bland, “DLL3 as a Candidate for Vertebral Mal-formations,” American Journal of Medical Genetics, Vol. 140A, No. 22, 2006, pp. 2447-2453. doi:10.1002/ajmg.a.31509
[8] P. F. Giampietro, C. L. Raggio and R. D. Blank, “Synteny- Defined Candidate Genes for Idiopathic and Congenital Scoliosis,” American Journal of Medical Genetics, Vol. 83, No. 3, 1999, pp. 164-177. doi:10.1002/(SICI)1096-8628(19990319)83:3<164::AID-AJMG5>3.0.CO;2-D
[9] P. F. Giampietro, C. L. Raggio, C. E. Reynolds, S. K. Shukla, E. McPherson, N. Ghebranious, F. S. Jacobsen, V. Kumar, T. Faciszewski, R. M. Pauli, K. Rasmussen, J. K. Burmester, C. Zaleski, S. Merchant, D. David, J. L. Weber, I. Glurich and R. D. Blank, “An Analysis of PAX1 in the Development of Vertebral Malformations,” Clinical Genetics, Vol. 68, No. 5, 2005, pp. 448-453. doi:10.1111/j.1399-0004.2005.00520.x
[10] K. J. Alden, B. Marosy, N. Nzegwu, C. M. Justice, A. F. Wilson and N. H.Miller, “Idiopathic Scoliosis: Identification of Can-didate Regions on Chromosome 19, p13,” Spine, Vol. 31, No. 16, 2006, pp. 1815-1819. doi:10.1097/01.brs.0000227264.23603.dc
[11] X. Gao, D. Gordon, D. Zhang, R. Browne, C. Helms, J. Gillum, S. Weber, S. Devroy, S. Swaney, M. Dobbs, J. Morcuende, V. Sheffield, M. Lovett, A. Bowcock, J. Herring and C. Wise, “CHD7 Gene Polymorphisms Are Associated with Susceptibility to Idiopathic Scoliosis,” American Journal of Human Genetics, Vol. 80, No. 5, 2007, pp. 957-965. doi:10.1086/513571
[12] N. H. Miller, C. M. Justice, B. Marosy, K. F. Doheny, E. Pugh, J. Zhang, H. C. Dietz 3rd and A. F. Wilson, “Identification of Candidate Regions for Familial Idiopathic Scoliosis,” Spine, Vol. 30, No. 10, 2005, pp. 1181-1187. doi:10.1097/01.brs.0000162282.46160.0a
[13] N. H. Miller, B. Marosy, C. M. Justice, S. M. Novak, E. Y. Tang, P. Boyce, J. Pettengil, K. F. Doheny, E. W. Pugh and A. F. Wilson, “Linkage Analysis of Genetic Loci for Kyphoscoliosis on Chromosomes 5, p13,” 13q13.3, and 13q32,” American Journal of Medical Genetics A, Vol. 140, No. 10, 2006, pp. 1059-1068. doi:10.1002/ajmg.a.31211
[14] V. Subramanian, B. I. Meyer and P. Gruss, “Disruption of the Murine Homeo-box Gene Cdx1 Affects Axial Skeletal Identities by Al-tering the Mesodermal Expression Domains of Hox Genes,” Cell, Vol. 83, No. 4, 1995, pp. 641-653. doi:10.1016/0092-8674(95)90104-3
[15] W. J. Murphy, D. M. Larkin, A. Evertsvan der Wind, G. Bourque, G. Tesler, L. Auvil, J. E. Beever, B. P. Chowdhary, F. Gali-bert, L. Gatzke, C. Hitte, S. N. Meyers, D. Milan, E. A. Ostrander, G. Pape, H. G. Parker, T. Raudsepp, M. B. Roqatcheva, L. B. Schook, L. C. Skow, M. Welge, J. E. Womack, S. J. O’brien, P. A. Pevzner and H. A. Lewin, “Dynamics of Mammalian Chromosome Evolution Inferred from Multispecies Comparative Maps,” Science, Vol. 309, No. 5734, 2005, pp. 613-617. doi:10.1126/science.1111387
[16] ensemble.org
[17] E. Skovlund and G. U. Fenstad, “Should We Always Choose a Nonparametric Test When Comparing Two Apparently Nonnormal Distributions?” Journal of clinical epidemi-ology, Vol. 54, No. 1, 2001, pp. 86-92. doi:10.1016/S0895-4356(00)00264-X
[18] A. V. Smith, D. J. Thomas, H. M. Munro and G. R. Abecasis, “Se-quence Features in Regions of Weak and Strong Linkage Disequilibrium,” Genome Research, Vol. 15, No. 11, 2005, pp. 1519-1534. doi:10.1101/gr.4421405
[19] D. M. Larkin, G. Pape, R. Donthu, L. Auvil, M. Welge and H. A. Lewin, “Breakpoint Regions and Homologous Synteny Blocks in Chromosomes Have Different Evolutionary Histories,” Genome Research, Vol. 19, No. 5, 2009, pp. 770-777. doi:10.1101/gr.086546.108
[20] evolution.gs.org
[21] A. Theodosiou, S. Arhondakis, M. Baumann and S. Kossida, “Evolutionary Scenarios of Notch Proteins,” Molecular Biology and Evolution, Vol. 26, No. 7, 2009, pp. 1631-1640. doi:10.1093/molbev/msp075
[22] K. Takacs-Vellai, T. Vellai, E. B. Chen, Y. Zhang, F. Guerry, M. J. Stern and F. Muller, “Transcriptional Control of Notch Signaling by a HOX and a PBX/EXD Protein during Vulval Development in C. elegans,” Developmental Biology, Vol. 302, No. 2, 2007, pp. 661-669. doi:10.1016/j.ydbio.2006.09.049
[23] X. Coumoul and C. X. Deng, “Roles of FGF Receptors in Mammalian Development and Congenital Diseases,” Birth Defects Research C: Embryo Today, Vol. 69, No. 4, 2003, pp. 286-304. doi:10.1002/bdrc.10025
[24] R. Alvarez-Medina, J. Cayuso, T. Okubo, S. Takada and E. Marti, “Wnt Canonical Pathway Restricts Graded Shh/Gli Pat-terning Activity through the Regulation of Gli 3 Expres-sion,” Development, Vol. 135, 2008, pp. 237- 247. doi:10.1242/dev.012054
[25] T. Gridley, “Notch Signal-ing and Inherited Human Disease Syndromes,” Human Molecular Genetics, Vol. 12, No. 1, 2003, pp. R9-R13. doi:10.1093/hmg/ddg052
[26] Y. G. Yueh, D. P. Gardner and C. Kappen, “Evidence for Regulation of Cartilage Differentiation by the Homeobox Gene Hoxc-8,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 17, 1998, pp. 9956-9961. doi:10.1073/pnas.95.17.9956
[27] F. Apiou, D. Flagiello, C. Cillo, B. Malfoy, M. F. Poupon and B. Dutrillaux, “Fine Mapping of Human HOX Gene Clusters,” Cytogenetics and Cell Genetics, Vol. 73, No. 1-2, 1996, pp. 114-115. doi:10.1159/000134320
[28] M. Kessel and P. Gruss, “Murine Developmental Control Genes,” Science, Vol. 249, No. 4967, 1990, pp. 374-379. doi:10.1126/science.1974085
[29] H. Peters, B. Wilm, N. Sakai, K. Imai, R. Mass and R. Balling, “Pax1 and Pax9 Synergistically Regulate Vertebral Column Development,” Development, Vol. 126, 1999, pp. 5399-5408.
[30] M. L. Basch, M. Bronner-Fraser and M. I. Garcia-Castro, “Specification of the Neural Crest Occurs during Gastrulation and Requires Pax7,” Nature, Vol. 441, No. 7090, 2006, pp. 218-222. doi:10.1038/nature04684
[31] F. Relaix, D. Rocancourt, A. Mansouri and M. Buckingham, “A Pax3/Pax7-Dependent Population of Skeletal Muscle Progenitor Cells,” Nature, Vol. 435, No. 7044, 2005, pp. 948-953. doi:10.1038/nature03594
[32] J. Brennan, C. C. Lu, D P. Norris, T. A. Rodriguez, R. S. Beddington and E. J. Robertson, “Nodal Signaling in the Epiblast Patterns the Early Mouse Embryo,” Nature, Vol. 411, No. 6840, 2001, pp. 965-969. doi:10.1038/35082103
[33] M. O. Baffi, M. A. Moran and R. Serra, “Tgfbr2 Regulates the Maintenance of Boundaries in the Axial Skeleton,” Developmental Biology, Vol. 296, No. 2, 2006, pp. 363-374. doi:10.1016/j.ydbio.2006.06.002
[34] J. T. Eggenschwiler, E. Espinoza and K. V. Anderson, “Rab23 Is an Essential Negative Regulator of the Mouse Sonic Hedgehog Signalling Pathway,” Nature, Vol. 412, No. 6843, 2001, pp. 194-198. doi:10.1038/35084089
[35] A. Vortkamp, K. Lee, B. Lanske, G. V. Segre, H. M. Kronenberg and C. J. Tabin, “Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein [See Comments],” Science, Vol. 273, No. 5275, 1996, pp. 613-622. doi:10.1126/science.273.5275.613
[36] T. Kanda, Y. Yoshida, Y. Izu, A. Nifuji, Y. Ezura, K. Nakashima and M. Noda, “PlexinD1 Deficiency Induces Defects in Axial Skeletal Morphogenesis,” Journal of Cellular Biochemistry, Vol. 101, No. 6, 2007, pp. 1329- 1337. doi:10.1002/jcb.21306
[37] P. Bialek, B. Kern, X. Yang, M. Schrock, D. Sosic, N. Hong, H. Wu, K. Yu, D. M. Ornitz, E. N. Olson, M. J. Justice and G. Karsenty, “A Twist Code Determines the Onset of Osteoblast Differentiation,” Developmental Cell, Vol. 6, No. 3, 2004, pp. 423-435. doi:10.1016/S1534-5807(04)00058-9
[38] J. Aruga, K. Mizugishi, H. Koseki, K. Imai, R. Balling, T. Noda and K. Mikoshiba, “Zic1 Regulates the Patterning of Vertebral Arches in Cooperation with Gli3,” Mechanisms of De-velopment, Vol. 89, No. 1-2, 1999, pp. 141- 150. doi:10.1016/S0925-4773(99)00220-8
[39] D. Krakow, S. P. Robertson, L. M. King, T. Morgan, E. T. Sebald, C. Bertolotto, S. Wachsmann-Hogiu, D. Acuna, S. S. Shapiro, T. Takafuta, S. Aftimos, C. A. Kim, H. Firth, C. E. Steiner, V. Cormier-Daire, A. Superti Furga, L. Bonafe, J. M. Graham, A. Grix, C. A. Bacino, J. Allanson, M. G. Bialer, R. S. Lachman, D. L. Rimoin and D. H. Cohn, “Mutations in the Gene Encoding Filamin B Disrupt Vertebral Segmentation, Joint Formation and Skeletogenesis,” Nature Genetics, Vol. 36, No. 4, 2004, pp. 405-410. doi:10.1
[40] B. Thomsen, P. Horn, F. Panitz, E. Bendixen, A. H. Petersen, L. E. Holm, V. H. Nielsen, J. S. Agerholm, J. Arnbjerg and C. Bendixen, “A Missense Mutation in the Bovine SLC35A3 Gene, Encoding a UDP-N-acetylgluco- samine Transporter, Causes Complex Vertebral Malformation,” Genome Research, Vol. 16, No. 1, 2006, pp. 97- 105. doi:10.1101/gr.3690506
[41] S. Yokoyama, Y. Ito, H. Ueno-Kudoh, H. Shimizu, K. Uchibe, S. Albini, K. Mitsuoka, S. Miyaki, M. Kiso, A. Nagai, T. Kikata, T. Osada, N. Fukuda, S. Yamashita, D. Harada, V. Mezzano, M. Kasai, P. L. Puri, Y. Hayashizaki, H. Okado, M. Hashimoto and H. Ashara, “A Systems Approach Reveals That the Myogenesis Genome Network Is Regulated by the Transcriptional Repressor RP58,” Developmental Cell, Vol. 17, No. 6, 2009, pp. 836-848. doi:10.1016/j.devcel.2009.10.011
[42] P. Soriano, “The PDGF Alpha Receptor Is Required for Neural Crest Cell Development and for Normal Patterning of the Somites,” Development, Vol. 124, No. 14, 1997, pp. 2691-2700.
[43] D. Chapman, A. Cooper-Morgan, Z. Harrelson and V. Papaioannou, “Critical Role for Tbx6 in Mesoderm Specification in the Mouse Embryo,” Me-chanisms of Development, Vol. 120, No. 7, 2003, pp. 837-847. doi:10.1016/S0925-4773(03)00066-2
[44] C. Keegan, J. Hutz, T. Else, M. Adamska, S. Shah, A. Kent, J. Howes, W. Beamer and G. Hammer, “Urogenital and Caudal Dysgenesis in Adrenocortical Dysplasia (acd) Is Caused by a Splicing Mutation in a Novel Telomeric Regulator,” Human Molecular Genetics, Vol. 14, 2005, pp. 113-123. doi:10.1093/hmg/ddi011
[45] N. A. Quaderi, S. Schweiger, K. Gaudenz, B. Franco, E. I. Rugarli, W. Berger, G. J. Feldman, M. Volta, G. Andolfi, S. Gilgen-krantz, R. W. Marion, R. C. Hennekam, J. M. Optiz, M. Muenke, H. H. Ropers and A. Ballabio, “Opitz G/BBB Syndrome, a Defect of Midline Development, Is Due to Mutations in a New RING Finger Gene on Xp22,” Nature Genetics, Vol. 17, No. 3, 1997, pp. 285-291. doi:10.1038/ng1197-285

  
comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.