Login Register Cart 0
Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Analysis of Inter-Chromosomal Distribution of Disease-Related Genes in Human Genome

Author(s): Xiaochao Sun, Bin Yang* and Qunye Zhang*

Volume 21, Issue 11, 2020

Page: [1068 - 1077] Pages: 10

DOI: 10.2174/1389203721666200426233158

Price: $65

Abstract

Many studies have shown that the spatial distribution of genes within a single chromosome exhibits distinct patterns. However, little is known about the characteristics of inter-chromosomal distribution of genes (including protein-coding genes, processed transcripts and pseudogenes) in different genomes. In this study, we explored these issues using the available genomic data of both human and model organisms. Moreover, we also analyzed the distribution pattern of protein-coding genes that have been associated with 14 common diseases and the insert/deletion mutations and single nucleotide polymorphisms detected by whole genome sequencing in an acute promyelocyte leukemia patient. We obtained the following novel findings. Firstly, inter-chromosomal distribution of genes displays a nonstochastic pattern and the gene densities in different chromosomes are heterogeneous. This kind of heterogeneity is observed in genomes of both lower and higher species. Secondly, protein-coding genes involved in certain biological processes tend to be enriched in one or a few chromosomes. Our findings have added new insights into our understanding of the spatial distribution of genome and disease- related genes across chromosomes. These results could be useful in improving the efficiency of disease-associated gene screening studies by targeting specific chromosomes.

Keywords: Inter-chromosomal distribution, gene, protein-coding, disease-associated, non-stochastic pattern, density, DNA.

« Previous Next »
Graphical Abstract

[1]
Ruban, A.; Schmutzer, T.; Scholz, U.; Houben, A. How Next-Generation Sequencing Has Aided Our Understanding of the Sequence Composition and Origin of B Chromosomes. Genes (Basel), 2017, 8(11), 294.
[http://dx.doi.org/10.3390/genes8110294] [PMID: 29068386]
[2]
Cacheux, L.; Ponger, L.; Gerbault-Seureau, M.; Loll, F.; Gey, D.; Richard, F.A.; Escudé, C. The Targeted Sequencing of Alpha Satellite DNA in Cercopithecus pogonias Provides New Insight Into the Diversity and Dynamics of Centromeric Repeats in Old World Monkeys. Genome Biol. Evol., 2018, 10(7), 1837-1851.
[http://dx.doi.org/10.1093/gbe/evy109] [PMID: 29860303]
[3]
Córdoba, M.; Rodriguez-Quiroga, S.A.; Vega, P.A.; Salinas, V.; Perez-Maturo, J.; Amartino, H.; Vásquez-Dusefante, C.; Medina, N.; González-Morón, D.; Kauffman, M.A. Whole exome sequencing in neurogenetic odysseys: An effective, cost- and time-saving diagnostic approach. PLoS One, 2018, 13(2)e0191228
[http://dx.doi.org/10.1371/journal.pone.0191228] [PMID: 29389947]
[4]
Excoffier, L. Patterns of DNA sequence diversity and genetic structure after a range expansion: lessons from the infinite-island model. Mol. Ecol., 2004, 13(4), 853-864.
[http://dx.doi.org/10.1046/j.1365-294X.2003.02004.x] [PMID: 15012760]
[5]
Colbran, L.L.; Chen, L.; Capra, J.A. Short DNA sequence patterns accurately identify broadly active human enhancers. BMC Genomics, 2017, 18(1), 536.
[http://dx.doi.org/10.1186/s12864-017-3934-9] [PMID: 28716036]
[6]
Wang, X.; Moazed, D. DNA sequence-dependent epigenetic inheritance of gene silencing and histone H3K9 methylation. Science, 2017, 356(6333), 88-91.
[http://dx.doi.org/10.1126/science.aaj2114] [PMID: 28302794]
[7]
Surrallés, J.; Sebastian, S.; Natarajan, A.T. Chromosomes with high gene density are preferentially repaired in human cells. Mutagenesis, 1997, 12(6), 437-442.
[http://dx.doi.org/10.1093/mutage/12.6.437] [PMID: 9412997]
[8]
Nekrutenko, A.; Li, W.H. Assessment of compositional heterogeneity within and between eukaryotic genomes. Genome Res., 2000, 10(12), 1986-1995.
[http://dx.doi.org/10.1101/gr.10.12.1986] [PMID: 11116093]
[9]
Oliver, J.L.; Bernaola-Galván, P.; Carpena, P.; Román-Roldán, R. Isochore chromosome maps of eukaryotic genomes. Gene, 2001, 276(1-2), 47-56.
[http://dx.doi.org/10.1016/S0378-1119(01)00641-2] [PMID: 11591471]
[10]
Saccone, S.; Federico, C.; Bernardi, G. Localization of the gene-richest and the gene-poorest isochores in the interphase nuclei of mammals and birds. Gene, 2002, 300(1-2), 169-178.
[http://dx.doi.org/10.1016/S0378-1119(02)01038-7] [PMID: 12468098]
[11]
Federico, C.; Scavo, C.; Cantarella, C.D.; Motta, S.; Saccone, S.; Bernardi, G. Gene-rich and gene-poor chromosomal regions have different locations in the interphase nuclei of cold-blooded vertebrates. Chromosoma, 2006, 115(2), 123-128.
[http://dx.doi.org/10.1007/s00412-005-0039-z] [PMID: 16404627]
[12]
Bickmore, W.A.; Teague, P. Influences of chromosome size, gene density and nuclear position on the frequency of constitutional translocations in the human population. Chromosome Res., 2002, 10(8), 707-715.
[http://dx.doi.org/10.1023/A:1021589031769] [PMID: 12575798]
[13]
Boutanaev, A.M.; Mikhaylova, L.M.; Nurminsky, D.I. The pattern of chromosome folding in interphase is outlined by the linear gene density profile. Mol. Cell. Biol., 2005, 25(18), 8379-8386.
[http://dx.doi.org/10.1128/MCB.25.18.8379-8386.2005] [PMID: 16135824]
[14]
Boyle, S.; Gilchrist, S.; Bridger, J.M.; Mahy, N.L.; Ellis, J.A.; Bickmore, W.A. The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum. Mol. Genet., 2001, 10(3), 211-219.
[http://dx.doi.org/10.1093/hmg/10.3.211] [PMID: 11159939]
[15]
Mayer, R.; Brero, A.; von Hase, J.; Schroeder, T.; Cremer, T.; Dietzel, S. Common themes and cell type specific variations of higher order chromatin arrangements in the mouse. BMC Cell Biol., 2005, 6, 44.
[http://dx.doi.org/10.1186/1471-2121-6-44] [PMID: 16336643]
[16]
Bonnefond, A.; Philippe, J.; Durand, E.; Dechaume, A.; Huyvaert, M.; Montagne, L.; Marre, M.; Balkau, B.; Fajardy, I.; Vambergue, A.; Vatin, V.; Delplanque, J.; Le Guilcher, D.; De Graeve, F.; Lecoeur, C.; Sand, O.; Vaxillaire, M.; Froguel, P. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One, 2012, 7(6)e37423
[http://dx.doi.org/10.1371/journal.pone.0037423] [PMID: 22701567]
[17]
Li, H.; Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics, 2009, 25(14), 1754-1760.
[http://dx.doi.org/10.1093/bioinformatics/btp324] [PMID: 19451168]
[18]
Li, H.; Handsaker, B.; Wysoker, A.; Fennell, T.; Ruan, J.; Homer, N.; Marth, G.; Abecasis, G.; Durbin, R. 1000 Genome Project Data Processing Subgroup. The Sequence alignment/map (SAM) format and SAMtools. Bioinformatics, 2009, 25, 2078-2079.
[http://dx.doi.org/10.1093/bioinformatics/btp352] [PMID: 19505943]
[19]
Li, R.; Li, Y.; Fang, X.; Yang, H.; Wang, J.; Kristiansen, K.; Wang, J. SNP detection for massively parallel whole-genome resequencing. Genome Res., 2009, 19(6), 1124-1132.
[http://dx.doi.org/10.1101/gr.088013.108] [PMID: 19420381]
[20]
Chen, K.; Wallis, J.W.; McLellan, M.D.; Larson, D.E.; Kalicki, J.M.; Pohl, C.S.; McGrath, S.D.; Wendl, M.C.; Zhang, Q.; Locke, D.P.; Shi, X.; Fulton, R.S.; Ley, T.J.; Wilson, R.K.; Ding, L.; Mardis, E.R. BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat. Methods, 2009, 6(9), 677-681.
[http://dx.doi.org/10.1038/nmeth.1363] [PMID: 19668202]
[21]
Wang, K.; Li, M.; Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res., 2010, 38(16)e164
[http://dx.doi.org/10.1093/nar/gkq603] [PMID: 20601685]
[22]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[23]
Mi, H.; Huang, X.; Muruganujan, A.; Tang, H.; Mills, C.; Kang, D.; Thomas, P.D. PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements. Nucleic Acids Res., 2017, 45(D1), D183-D189.
[http://dx.doi.org/10.1093/nar/gkw1138] [PMID: 27899595]
[24]
Guerra, C. Ingenuity Pathways Analysis: software for discovering and modelling pathways and networks in your systems data. Comp. Biochem. Physiol. A Mol. Integr. Physiol., 2008, 150(3), S50.
[http://dx.doi.org/10.1016/j.cbpa.2008.04.619]
[25]
Hurst, L.D.; Pál, C.; Lercher, M.J. The evolutionary dynamics of eukaryotic gene order. Nat. Rev. Genet., 2004, 5(4), 299-310.
[http://dx.doi.org/10.1038/nrg1319] [PMID: 15131653]
[26]
Michalak, P. Coexpression, coregulation, and cofunctionality of neighboring genes in eukaryotic genomes. Genomics, 2008, 91(3), 243-248.
[http://dx.doi.org/10.1016/j.ygeno.2007.11.002] [PMID: 18082363]
[27]
Saccone, C.; Pesole, G. Handbook of Comparative Genomics: Principles and Methodology; Wiley & Sons: New York, 2005.
[28]
Yi, G.; Sze, S.H.; Thon, M.R. Identifying clusters of functionally related genes in genomes. Bioinformatics, 2007, 23(9), 1053-1060.
[http://dx.doi.org/10.1093/bioinformatics/btl673] [PMID: 17237058]
[29]
Raghupathy, N.; Durand, D. Gene cluster statistics with gene families. Mol. Biol. Evol., 2009, 26(5), 957-968.
[http://dx.doi.org/10.1093/molbev/msp002] [PMID: 19150803]
[30]
Segal, E.; Shapira, M.; Regev, A.; Pe’er, D.; Botstein, D.; Koller, D.; Friedman, N. Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data. Nat. Genet., 2003, 34(2), 166-176.
[http://dx.doi.org/10.1038/ng1165] [PMID: 12740579]
[31]
Purmann, A.; Toedling, J.; Schueler, M.; Carninci, P.; Lehrach, H.; Hayashizaki, Y.; Huber, W.; Sperling, S. Genomic organization of transcriptomes in mammals: Coregulation and cofunctionality. Genomics, 2007, 89(5), 580-587.
[http://dx.doi.org/10.1016/j.ygeno.2007.01.010] [PMID: 17369017]
[32]
Lawrence, J.G. Gene organization: selection, selfishness, and serendipity. Annu. Rev. Microbiol., 2003, 57, 419-440.
[http://dx.doi.org/10.1146/annurev.micro.57.030502.090816] [PMID: 14527286]
[33]
Lefthériotis, G.; Omarjee, L.; Le Saux, O.; Henrion, D.; Abraham, P.; Prunier, F.; Willoteaux, S.; Martin, L. The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification. Front. Genet., 2013, 4, 4.
[http://dx.doi.org/10.3389/fgene.2013.00004] [PMID: 23408347]
[34]
Glass, R.I.; Gentsch, J.R. Rotaviruses: Methods and Protocols: Edited by James Gray and Ulrich Desselberger.Clinical Infectious Diseases; Humana Press: Totowa, NJ, 2000, p. 261. illustrated..
[35]
McGranahan, N.; Swanton, C. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell, 2015, 27(1), 15-26.
[http://dx.doi.org/10.1016/j.ccell.2014.12.001] [PMID: 25584892]
[36]
Cooper, D.N.; Ball, E.V.; Mort, M. Chromosomal distribution of disease genes in the human genome. Genet. Test. Mol. Biomarkers, 2010, 14(4), 441-446.
[http://dx.doi.org/10.1089/gtmb.2010.0081] [PMID: 20642358]

Rights & Permissions Print Cite
Article Metrics
32
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy