The Medical Genome Project (MGP) was has been the first regional genomics project carried out in Spain, early in 2010, when most of the technology around genomics sequencing was in a very preliminary stage of development. MGP was a pioneer study in which the sequencing of exomes of hundreds of rare diseases patients and control individuals was determined and used to develop the technologies that ultimately speeded up the laborious process of detection of disease genes. The MGP has produced a number of publications as well as fostered the development of different innovative methodologies for the management of human genomic data, that were further used in different research and clinical settings and some of which awarded.


Javier Santoyo, former scientific supervisor and manager of the MPG:


Tools for the diagnostic of inherited diseases based on the genomic sequence of the patient (variant discovery and prioritization system). The Interactive Variant Analysis (IVA-MMP) tool based in the OpenCB genomic data management engine, which we started to develop during the MGP and now is one of the tools of the 100.000 genomes project UK ( This software was used within the CIBERER ( to centralize the analysis of the EnoD (undiagnosed diseases) project (

The Collaborative Spanish Variant Server, CSVS, was created to provide information about the variability of the Spanish population to the scientific/medical community. It is useful for filtering polymorphisms and local variations in the process of prioritizing candidate disease genes. CSVS currently stores information on almost 2000 unrelated Spanish individuals.


The first map of the genetic variability of the healthy Spanish population

Beyond the specific finding on particular diseases, one of the major achievements of the MGP project was the generation of the first map of genetic variability of the Spanish population. This map in available in the CSVS (see above) and was published (Dopazo et al., 2016; see below). In order to make this information available to the scientific community by complying with the data protection regulation (GDPR), we deposited the data in the EGA database ( under the EGA study ID: EGAS00001000938 ( EGA provides restricted access via a DAC (Data Access Committee), which safeguards that the use requested is GDPR compliant, to researchers interested in using these data in studies.



The first description of the genetic background of the healthy Spanish population, arisen from the MGP and published (Dopazo et al., Mol Biol Evol. 2016) was awarded in 2017 by the Medical College of Cordoba: The development of the bioinformatic tools for discovering disease genes and determining diagnostic variants (Aleman et al., 2014a NAR; Aleman et al., 2014b NAR) was also awarded by Cajasol in 2018 as the most innovative proposal in health research:

The development of the bioinformatic tools for discovering disease genes and determining diagnostic variants (Aleman et al., 2014a NAR; Aleman et al., 2014b NAR) was also awarded by Cajasol in 2018 as the most innovative proposal in health research:


Publications on bioinformatic tools

López-Domingo FJ, Florido JP, Rueda A1, Dopazo J, Santoyo-Lopez J. ngsCAT: a tool to assess the efficiency of targeted enrichment sequencing. Bioinformatics. 2014 Jun 15;30(12):1767-8. doi: 10.1093/bioinformatics/btu108.

Alemán A, Garcia-Garcia F, Medina I, Dopazo J. A web tool for the design and management of panels of genes for targeted enrichment and massive sequencing for clinical applications. Nucleic Acids Res. 2014 Jul;42(Web Server issue):W83-7. doi: 10.1093/nar/gku472

Alemán A, Garcia-Garcia F, Salavert F, Medina I, Dopazo J. A web-based interactive framework to assist in the prioritization of disease candidate genes in whole-exome sequencing studies. Nucleic Acids Res. 2014 Jul;42(Web Server issue):W88-93. doi: 10.1093/nar/gku407.


Publications on results of the project

Gui H, Schriemer D, Cheng WW, Chauhan RK, Antiňolo G, Berrios C, Bleda M, Brooks AS, Brouwer RW, Burns AJ, Cherny SS, Dopazo J, Eggen BJ, Griseri P, Jalloh B, Le TL, Lui VC, Luzón-Toro B, Matera I, Ngan ES, Pelet A, Ruiz-Ferrer M, Sham PC, Shepherd IT, So MT, Sribudiani Y, Tang CS, van den Hout MC, van der Linde HC, van Ham TJ, van IJcken WF, Verheij JB, Amiel J, Borrego S, Ceccherini I, Chakravarti A, Lyonnet S, Tam PK, Garcia-Barceló MM, Hofstra RM. Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes. Genome Biol. 2017 Mar 8;18(1):48. doi: 10.1186/s13059-017-1174-6.

Lagarde J, Uszczynska-Ratajczak B, Santoyo-Lopez J, Gonzalez JM, Tapanari E, Mudge JM, Steward CA, Wilming L, Tanzer A, Howald C, Chrast J, Vela-Boza A, Rueda A, Lopez-Domingo FJ, Dopazo J, Reymond A, Guigó R, Harrow J. Extension of human lncRNA transcripts by RACE coupled with long-read high-throughput sequencing (RACE-Seq). Nat Commun. 2016 Aug 17;7:12339. doi: 10.1038/ncomms12339.

Bravo-Gil N, Méndez-Vidal C, Romero-Pérez L, González-del Pozo M, Rodríguez-de la Rúa E, Dopazo J, Borrego S, Antiñolo G. Improving the management of Inherited Retinal Dystrophies by targeted sequencing of a population-specific gene panel. Sci Rep. 2016 Apr 1;6:23910. doi: 10.1038/srep23910.

Dopazo J, Amadoz A, Bleda M, Garcia-Alonso L, Alemán A, García-García F, Rodriguez JA, Daub JT, Muntané G, Rueda A, Vela-Boza A, López-Domingo FJ, Florido JP, Arce P, Ruiz-Ferrer M, Méndez-Vidal C, Arnold TE, Spleiss O, Alvarez-Tejado M, Navarro A, Bhattacharya SS, Borrego S, Santoyo-López J, Antiñolo G. 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation. Mol Biol Evol. 2016 May;33(5):1205-18. doi: 10.1093/molbev/msw005. Epub 2016 Jan 13.

This paper was awarded by the Medical College of Cordoba:

Luzón-Toro B, Bleda M, Navarro E, García-Alonso L, Ruiz-Ferrer M, Medina I, Martín-Sánchez M, Gonzalez CY, Fernández RM, Torroglosa A, Antiñolo G, Dopazo J, Borrego S. Identification of epistatic interactions through genome-wide association studies in sporadic medullary and juvenile papillary thyroid carcinomas. BMC Med Genomics. 2015 Dec 21;8:83. doi: 10.1186/s12920-015-0160-7.

Luzón-Toro B, Gui H, Ruiz-Ferrer M, Sze-Man Tang C, Fernández RM, Sham PC, Torroglosa A, Kwong-Hang Tam P, Espino-Paisán L, Cherny SS, Bleda M, Enguix-Riego Mdel V, Dopazo J, Antiñolo G, García-Barceló MM, Borrego S. Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease. Sci Rep. 2015 Nov 12;5:16473. doi: 10.1038/srep16473.

Pozo MG, Bravo-Gil N, Méndez-Vidal C, Montero-de-Espinosa I, Millán JM, Dopazo J, Borrego S, Antiñolo G. Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F. Am J Med Genet A. 2015 Jul;167(7):1597-600. doi: 10.1002/ajmg.a.37003. Epub 2015 Mar 30.

González-del Pozo M, Méndez-Vidal C, Bravo-Gil N, Vela-Boza A, Dopazo J, Borrego S, Antiñolo G. Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies. PLoS One. 2014 Dec 29;9(12):e116176. doi: 10.1371/journal.pone.0116176.

Méndez-Vidal C, Bravo-Gil N, González-Del Pozo M, Vela-Boza A, Dopazo J, Borrego S, Antiñolo G. Novel RP1 mutations and a recurrent BBS1 variant explain the co-existence of two distinct retinal phenotypes in the same pedigree. BMC Genet. 2014 Dec 14;15:143. doi: 10.1186/s12863-014-0143-2.

Garcia-Alonso L, Jiménez-Almazán J, Carbonell-Caballero J, Vela-Boza A, Santoyo-López J, Antiñolo G, Dopazo J. The role of the interactome in the maintenance of deleterious variability in human populations. Mol Syst Biol. 2014 Sep 26;10:752. doi: 10.15252/msb.20145222.

González-Del Pozo M, Méndez-Vidal C, Santoyo-Lopez J, Vela-Boza A, Bravo-Gil N, Rueda A, García-Alonso L, Vázquez-Marouschek C, Dopazo J, Borrego S, Antiñolo G. Deciphering intrafamilial phenotypic variability by exome sequencing in a Bardet-Biedl family. Mol Genet Genomic Med. 2014 Mar;2(2):124-33. doi: 10.1002/mgg3.50. Epub 2013 Dec 3.

Fernández RM, Bleda M, Luzón-Toro B, García-Alonso L, Arnold S, Sribudiani Y, Besmond C, Lantieri F, Doan B, Ceccherini I, Lyonnet S, Hofstra RM, Chakravarti A, Antiñolo G, Dopazo J, Borrego S. Pathways systematically associated to Hirschsprung's disease. Orphanet J Rare Dis. 2013 Dec 2;8:187. doi: 10.1186/1750-1172-8-187.

Méndez-Vidal C, González-Del Pozo M, Vela-Boza A, Santoyo-López J, López-Domingo FJ, Vázquez-Marouschek C, Dopazo J, Borrego S, Antiñolo G. Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa. Mol Vis. 2013 Nov 7;19:2187-95.

Fernández RM, Bleda M, Núñez-Torres R, Medina I, Luzón-Toro B, García-Alonso L, Torroglosa A, Marbà M, Enguix-Riego MV, Montaner D, Antiñolo G, Dopazo J, Borrego S. Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung's disease. Orphanet J Rare Dis. 2012 Dec 28;7:103. doi: 10.1186/1750-1172-7-103.

Carbonell J, Alloza E, Arce P, Borrego S, Santoyo J, Ruiz-Ferrer M, Medina I, Jiménez-Almazán J, Méndez-Vidal C, González-Del Pozo M, Vela A, Bhattacharya SS, Antiñolo G, Dopazo J. A map of human microRNA variation uncovers unexpectedly high levels of variability. Genome Med. 2012 Aug 24;4(8):62. doi: 10.1186/gm363.

González-del Pozo M, Borrego S, Barragán I, Pieras JI, Santoyo J, Matamala N, Naranjo B, Dopazo J, Antiñolo G. Mutation screening of multiple genes in Spanish patients with autosomal recessive retinitis pigmentosa by targeted resequencing. PLoS One. 2011;6(12):e27894. doi: 10.1371/journal.pone.0027894.

Barragán I, Borrego S, Pieras JI, González-del Pozo M, Santoyo J, Ayuso C, Baiget M, Millan JM, Mena M, Abd El-Aziz MM, Audo I, Zeitz C, Littink KW, Dopazo J, Bhattacharya SS, Antiñolo G. Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa. Hum Mutat. 2010 Nov;31(11):E1772-800.