Skip to main content
×
×
Home

ReMo-SNPs: a new software tool for identification of polymorphisms in regions and motifs genome-wide

  • LISETTE GRAAE (a1), SILVIA PADDOCK (a2) and ANDREA CARMINE BELIN (a1)
Summary

Studies of complex genetic diseases have revealed many risk factors of small effect, but the combined amount of heritability explained is still low. Genome-wide association studies are often underpowered to identify true effects because of the very large number of parallel tests. There is, therefore, a great need to generate data sets that are enriched for those markers that have an increased a priori chance of being functional, such as markers in genomic regions involved in gene regulation. ReMo-SNPs is a computational program developed to aid researchers in the process of selecting functional SNPs for association analyses in user-specified regions and/or motifs genome-wide. The useful feature of automatic selection of genotyped markers in the user-provided material makes the output data ready to be used in a following association study. In this article we describe the program and its functions. We also validate the program by including an example study on three different transcription factors and results from an association study on two psychiatric phenotypes. The flexibility of the ReMo-SNPs program enables the user to study any region or sequence of interest, without limitation to transcription factor binding regions and motifs. The program is freely available at: http://www.neuro.ki.se/ReMo-SNPs/

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      ReMo-SNPs: a new software tool for identification of polymorphisms in regions and motifs genome-wide
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      ReMo-SNPs: a new software tool for identification of polymorphisms in regions and motifs genome-wide
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      ReMo-SNPs: a new software tool for identification of polymorphisms in regions and motifs genome-wide
      Available formats
      ×
Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
* Corresponding author: Andrea.Carmine.Belin@ki.se
References
Hide All
Boomsma, D. I., Willemsen, G., Sullivan, P. F., Heutink, P., Meijer, P., Sondervan, D., Kluft, C., Smit, G., Nolen, W. A., Zitman, F. G., Smit, J. H., Hoogendijk, W. J., van Dyck, R., de Geus, E. J. & Penninx, B. W. (2008). Genome-wide association of major depression: description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects. European Journal of Human Genetics 16, 335342.
Boyle, A. P., Hong, E. L., Hariharan, M., Cheng, Y., Schaub, M. A., Kasowski, M., Karczewski, K. J., Park, J., Hitz, B. C., Weng, S., Cherry, J. M. & Snyder, M. (2012). Annotation of functional variation in personal genomes using RegulomeDB. Genome Research 22, 17901797.
Bulik-Sullivan, B., Selitsky, S. & Sethupathy, P. (2013). Prioritization of genetic variants in the microRNA regulome as functional candidates in genome-wide association studies. Human Mutation 34, 10491056.
Conde, L., Vaquerizas, J. M., Dopazo, H., Arbiza, L., Reumers, J., Rousseau, F., Schymkowitz, J. & Dopazo, J. (2006). PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes. Nucleic Acids Research 34, W621W625.
Degenhardt, T., Saramaki, A., Malinen, M., Rieck, M., Vaisanen, S., Huotari, A., Herzig, K. H., Muller, R. & Carlberg, C. (2007). Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta. Journal of Molecular Biology 372, 341355.
Frazer, K. A., Ballinger, D. G., Cox, D. R., Hinds, D. A., Stuve, L. L., Gibbs, R. A., Belmont, J. W., Boudreau, A., Hardenbol, P., Leal, S. M., Pasternak, S., Wheeler, D. A., Willis, T. D., Yu, F., Yang, H., Zeng, C., Gao, Y., Hu, H., Hu, W., Li, C., Lin, W., Liu, S., Pan, H., Tang, X., Wang, J., Wang, W., Yu, J., Zhang, B., Zhang, Q., Zhao, H., Zhao, H., Zhou, J., Gabriel, S. B., Barry, R., Blumenstiel, B., Camargo, A., Defelice, M., Faggart, M., Goyette, M., Gupta, S., Moore, J., Nguyen, H., Onofrio, R. C., Parkin, M., Roy, J., Stahl, E., Winchester, E., Ziaugra, L., Altshuler, D., Shen, Y., Yao, Z., Huang, W., Chu, X., He, Y., Jin, L., Liu, Y., Shen, Y., Sun, W., Wang, H., Wang, Y., Wang, Y., Xiong, X., Xu, L., Waye, M. M., Tsui, S. K., Xue, H., Wong, J. T., Galver, L. M., Fan, J. B., Gunderson, K., Murray, S. S., Oliphant, A. R., Chee, M. S., Montpetit, A., Chagnon, F., Ferretti, V., Leboeuf, M., Olivier, J. F., Phillips, M. S., Roumy, S., Sallee, C., Verner, A., Hudson, T. J., Kwok, P. Y., Cai, D., Koboldt, D. C., Miller, R. D., Pawlikowska, L., Taillon-Miller, P., Xiao, M., Tsui, L. C., Mak, W., Song, Y. Q., Tam, P. K., Nakamura, Y., Kawaguchi, T., Kitamoto, T., Morizono, T., Nagashima, A., Ohnishi, Y., Sekine, A., Tanaka, T., Tsunoda, T., Deloukas, P., Bird, C. P., Delgado, M., Dermitzakis, E. T., Gwilliam, R., Hunt, S., Morrison, J., Powell, D., Stranger, B. E., Whittaker, P., Bentley, D. R., Daly, M. J., de Bakker, P. I., Barrett, J., Chretien, Y. R., Maller, J., McCarroll, S., Patterson, N., Pe'er, I., Price, A., Purcell, S., Richter, D. J., Sabeti, P., Saxena, R., Schaffner, S. F., Sham, P. C., Varilly, P., Altshuler, D., Stein, L. D., Krishnan, L., Smith, A. V., Tello-Ruiz, M. K., Thorisson, G. A., Chakravarti, A., Chen, P. E., Cutler, D. J., Kashuk, C. S., Lin, S., Abecasis, G. R., Guan, W., Li, Y., Munro, H. M., Qin, Z. S., Thomas, D. J., McVean, G., Auton, A., Bottolo, L., Cardin, N., Eyheramendy, S., Freeman, C., Marchini, J., Myers, S., Spencer, C., Stephens, M., Donnelly, P., Cardon, L. R., Clarke, G., Evans, D. M., Morris, A. P., Weir, B. S., Tsunoda, T., Mullikin, J. C., Sherry, S. T., Feolo, M., Skol, A., Zhang, H., Zeng, C., Zhao, H., Matsuda, I., Fukushima, Y., Macer, D. R., Suda, E., Rotimi, C. N., Adebamowo, C. A., Ajayi, I., Aniagwu, T., Marshall, P. A., Nkwodimmah, C., Royal, C. D., Leppert, M. F., Dixon, M., Peiffer, A., Qiu, R., Kent, A., Kato, K., Niikawa, N., Adewole, I. F., Knoppers, B. M., Foster, M. W., Clayton, E. W., Watkin, J., Gibbs, R. A., Belmont, J. W., Muzny, D., Nazareth, L., Sodergren, E., Weinstock, G. M., Wheeler, D. A., Yakub, I., Gabriel, S. B., Onofrio, R. C., Richter, D. J., Ziaugra, L., Birren, B. W., Daly, M. J., Altshuler, D., Wilson, R. K., Fulton, L. L., Rogers, J., Burton, J., Carter, N. P., Clee, C. M., Griffiths, M., Jones, M. C., McLay, K., Plumb, R. W., Ross, M. T., Sims, S. K., Willey, D. L., Chen, Z., Han, H., Kang, L., Godbout, M., Wallenburg, J. C., L'Archeveque, P., Bellemare, G., Saeki, K., Wang, H., An, D., Fu, H., Li, Q., Wang, Z., Wang, R., Holden, A. L., Brooks, L. D., McEwen, J. E., Guyer, M. S., Wang, V. O., Peterson, J. L., Shi, M., Spiegel, J., Sung, L. M., Zacharia, L. F., Collins, F. S., Kennedy, K., Jamieson, R. & Stewart, J. (2007). A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851861.
Graae, L., Karlsson, R. & Paddock, S. (2012). Significant association of estrogen receptor binding site variation with bipolar disorder in females. PLoS One 7, e32304.
Guo, Y. & Jamison, D. C. (2005). The distribution of SNPs in human gene regulatory regions. BMC Genomics 6, 140.
Heikkinen, S., Väisänen, S., Pehkonen, P., Seuter, S., Benes, V. & Carlberg, C. (2011). Nuclear hormone 1α,25-dihydroxyvitamin D3 elicits a genome-wide shift in the locations of VDR chromatin occupancy. Nucleic Acids Research 39, 91819193.
Hidalgo, A. A., Deeb, K. K., Pike, J. W., Johnson, C. S. & Trump, D. L. (2011). Dexamethasone enhances 1alpha,25-dihydroxyvitamin D3 effects by increasing vitamin D receptor transcription. The Journal of Biological Chemistry 286, 3622836237.
IJpenberg, A., Jeannin, E., Wahli, W. & Desvergne, B. (1997). Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element. The Journal of Biological Chemistry 272, 2010820117.
Juge-Aubry, C., Pernin, A., Favez, T., Burger, A. G., Wahli, W., Meier, C. A. & Desvergne, B. (1997). DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region. The Journal of Biological Chemistry 272, 2525225259.
Lin, C. Y., Vega, V. B., Thomsen, J. S., Zhang, T., Kong, S. L., Xie, M., Chiu, K. P., Lipovich, L., Barnett, D. H., Stossi, F., Yeo, A., George, J., Kuznetsov, V. A., Lee, Y. K., Charn, T. H., Palanisamy, N., Miller, L. D., Cheung, E., Katzenellenbogen, B. S., Ruan, Y., Bourque, G., Wei, C. L. & Liu, E. T. (2007). Whole-genome cartography of estrogen receptor alpha binding sites. PLoS Genetics 3, e87.
Lonsdale, J., Thomas, J., Salvatore, M., Phillips, R., Lo, E., Shad, S., Hasz, R., Walters, G., Garcia, F., Young, N., Foster, B., Moser, M., Karasik, E., Gillard, B., Ramsey, K., Sullivan, S., Bridge, J., Magazine, H., Syron, J., Fleming, J., Siminoff, L., Traino, H., Mosavel, M., Barker, L., Jewell, S., Rohrer, D., Maxim, D., Filkins, D., Harbach, P., Cortadillo, E., Berghuis, B., Turner, L., Hudson, E., Feenstra, K., Sobin, L., Robb, J., Branton, P., Korzeniewski, G., Shive, C., Tabor, D., Qi, L., Groch, K., Nampally, S., Buia, S., Zimmerman, A., Smith, A., Burges, R., Robinson, K., Valentino, K., Bradbury, D., Cosentino, M., Diaz-Mayoral, N., Kennedy, M., Engel, T., Williams, P., Erickson, K., Ardlie, K., Winckler, W., Getz, G., DeLuca, D., MacArthur, D., Kellis, M., Thomson, A., Young, T., Gelfand, E., Donovan, M., Meng, Y., Grant, G., Mash, D., Marcus, Y., Basile, M., Liu, J., Zhu, J., Tu, Z., Cox, N. J., Nicolae, D. L., Gamazon, E. R., Im, H. K., Konkashbaev, A., Pritchard, J., Stevens, M., Flutre, T., Wen, X., Dermitzakis, E. T., Lappalainen, T., Guigo, R., Monlong, J., Sammeth, M., Koller, D., Battle, A., Mostafavi, S., McCarthy, M., Rivas, M., Maller, J., Rusyn, I., Nobel, A., Wright, F., Shabalin, A., Feolo, M., Sharopova, N., Sturcke, A., Paschal, J., Anderson, J. M., Wilder, E. L., Derr, L. K., Green, E. D., Struewing, J. P., Temple, G., Volpi, S., Boyer, J. T., Thomson, E. J., Guyer, M. S., Ng, C., Abdallah, A., Colantuoni, D., Insel, T. R., Koester, S. E., Little, A. R., Bender, P. K., Lehner, T., Yao, Y., Compton, C. C., Vaught, J. B., Sawyer, S., Lockhart, N. C., Demchok, J. & Moore, H. F. (2013). The Genotype-Tissue Expression (GTEx) project. Nature Genetics 45, 580585.
Meyer, M. B., Goetsch, P. D. & Pike, J. W. (2012). VDR/RXR and TCF4/β-catenin cistromes in colonic cells of colorectal tumor origin: impact on c-FOS and c-MYC gene expression. Molecular Endocrinology 26, 3751.
Michalik, L., Auwerx, J., Berger, J. P., Chatterjee, V. K., Glass, C. K., Gonzalez, F. J., Grimaldi, P. A., Kadowaki, T., Lazar, M. A., O'Rahilly, S., Palmer, C. N., Plutzky, J., Reddy, J. K., Spiegelman, B. M., Staels, B. & Wahli, W. (2006). International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacological Reviews 58, 726741.
Pellegrini, M. & Ferrari, R. (2012). Epigenetic Analysis: ChIP-chip and ChIP-seq. In Next Generation Microarray Bioinformatics, p. 377. New York, NY: Humana Press.
Pico, A. R., Smirnov, I. V., Chang, J. S., Yeh, R. F., Wiemels, J. L., Wiencke, J. K., Tihan, T., Conklin, B. R. & Wrensch, M. (2009). SNPLogic: an interactive single nucleotide polymorphism selection, annotation, and prioritization system. Nucleic Acids Research 37, D803D809.
Ramagopalan, S. V., Heger, A., Berlanga, A. J., Maugeri, N. J., Lincoln, M. R., Burrell, A., Handunnetthi, L., Handel, A. E., Disanto, G., Orton, S. M., Watson, C. T., Morahan, J. M., Giovannoni, G., Ponting, C. P., Ebers, G. C. & Knight, J. C. (2010). A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Research 20, 13521360.
Reddy, T. E., Pauli, F., Sprouse, R. O., Neff, N. F., Newberry, K. M., Garabedian, M. J. & Myers, R. M. (2009). Genomic determination of the glucocorticoid response reveals unexpected mechanisms of gene regulation. Genome Research 19, 21632171.
Schaub, M. A., Boyle, A. P., Kundaje, A., Batzoglou, S. & Snyder, M. (2012). Linking disease associations with regulatory information in the human genome. Genome Research 22, 17481759.
Schmidt, S. F., Jörgensen, M., Chen, Y., Nielsen, R., Sandelin, A. & Mandrup, S. (2011). Cross species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites. BMC Genomics 12, 152.
Sherry, S. T., Ward, M. H., Kholodov, M., Baker, J., Phan, L., Smigielski, E. M. & Sirotkin, K. (2001). dbSNP: the NCBI database of genetic variation. Nucleic Acids Research 29, 308311.
Smith, E. N., Bloss, C. S., Badner, J. A., Barrett, T., Belmonte, P. L., Berrettini, W., Byerley, W., Coryell, W., Craig, D., Edenberg, H. J., Eskin, E., Foroud, T., Gershon, E., Greenwood, T. A., Hipolito, M., Koller, D. L., Lawson, W. B., Liu, C., Lohoff, F., McInnis, M. G., McMahon, F. J., Mirel, D. B., Murray, S. S., Nievergelt, C., Nurnberger, J., Nwulia, E. A., Paschall, J., Potash, J. B., Rice, J., Schulze, T. G., Scheftner, W., Panganiban, C., Zaitlen, N., Zandi, P. P., Zöllner, S., Schork, N. J. & Kelsoe, J. R. (2009). Genome-wide association study of bipolar disorder in European American and African American individuals. Molecular Psychiatry 14, 755763.
Sullivan, P. F., de Geus, E. J., Willemsen, G., James, M. R., Smit, J. H., Zandbelt, T., Arolt, V., Baune, B. T., Blackwood, D., Cichon, S., Coventry, W. L., Domschke, K., Farmer, A., Fava, M., Gordon, S. D., He, Q., Heath, A. C., Heutink, P., Holsboer, F., Hoogendijk, W. J., Hottenga, J. J., Hu, Y., Kohli, M., Lin, D., Lucae, S., Macintyre, D. J., Maier, W., McGhee, K. A., McGuffin, P., Montgomery, G. W., Muir, W. J., Nolen, W. A., Nöthen, M. M., Perlis, R. H., Pirlo, K., Posthuma, D., Rietschel, M., Rizzu, P., Schosser, A., Smit, A. B., Smoller, J. W., Tzeng, J. Y., van Dyck, R., Verhage, M., Zitman, F. G., Martin, N. G., Wray, N. R., Boomsma, D. I. & Penninx, B. W. (2009). Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Molecular Psychiatry 14, 359375.
Teng, M., Ichikawa, S., Padgett, L. R., Wang, Y., Mort, M., Cooper, D. N., Koller, D. L., Foroud, T., Edenberg, H. J., Econs, M. J. & Liu, Y. (2012). regSNPs: a strategy for prioritizing regulatory single nucleotide substitutions. Bioinformatics 28, 18791886.
The Encode Project Consortium (2012). An integrated encyclopedia of DNA elements in the human genome. Nature 489, 5774.
Vernot, B., Stergachis, A. B., Maurano, M. T., Vierstra, J., Neph, S., Thurman, R. E., Stamatoyannopoulos, J. A. & Akey, J. M. (2012). Personal and population genomics of human regulatory variation. Genome Research 22, 16891697.
Wang, P., Dai, M., Xuan, W., McEachin, R. C., Jackson, A. U., Scott, L. J., Athey, B., Watson, S. J. & Meng, F. (2006). SNP Function Portal: a web database for exploring the function implication of SNP alleles. Bioinformatics 22, e523e529.
Xu, Z. & Taylor, J. A. (2009). SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Research 37, W600W605.
Yuan, H. Y., Chiou, J. J., Tseng, W. H., Liu, C. H., Liu, C. K., Lin, Y. J., Wang, H. H., Yao, A., Chen, Y. T. & Hsu, C. N. (2006). FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization. Nucleic Acids Research 34, W635W641.
Zhang, J., Chalmers, M. J., Stayrook, K. R., Burris, L. L., Wang, Y., Busby, S. A., Pascal, B. D., Garcia-Ordonez, R. D., Bruning, J. B., Istrate, M. A., Kojetin, D. J., Dodge, J. A., Burris, T. P. & Griffin, P. R. (2011). DNA binding alters coactivator interaction surfaces of the intact VDR−RXR complex. Nature Structural & Molecular Biology 18, 556563.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Genetics Research
  • ISSN: 0016-6723
  • EISSN: 1469-5073
  • URL: /core/journals/genetics-research
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed