{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T23:11:40Z","timestamp":1765667500303,"version":"build-2065373602"},"reference-count":91,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMedInformatics"],"abstract":"<jats:p>Background: Runs of homozygosity (ROHs), continuous homozygous regions across the genome, are often linked to consanguinity, with their size and frequency reflecting shared parental ancestry. Homozygosity mapping (HM) leverages ROHs to identify genes associated with autosomal recessive diseases. Whole-exome sequencing (WES) improves HM by detecting ROHs and disease-causing variants. Methods: To streamline personalized multigene panel creation, using WES and ROHs, we developed a methodology integrating ROHMMCLI and HomozygosityMapper algorithms, and, optionally, Human Phenotype Ontology (HPO) terms, implemented in a Django Web application. Resorting to a dataset of 12,167 WES, we performed the first ROH profiling of the Portuguese population. Clustering models were applied to predict consanguinity from ROH features. Results: These resources were applied for the genetic characterization of two siblings with epilepsy, myoclonus and dystonia, pinpointing the CSTB gene as disease-causing. Using the 2021 Census population distribution, we created a representative sample (3941 WES) and measured genome-wide autozygosity (FROH). Portalegre, Viseu, Bragan\u00e7a, Madeira, and Vila Real districts presented the highest FROH scores. Multidimensional scaling showed that ROH count and sum were key predictors of consanguinity, achieving a test F1-score of 0.96 with additional features. Conclusions: This study contributes with new bioinformatics tools for ROH analysis in a clinical setting, providing unprecedented population-level ROH data for Portugal.<\/jats:p>","DOI":"10.3390\/biomedinformatics4040128","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T06:26:12Z","timestamp":1734416772000},"page":"2374-2399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of Regions of Homozygosity: Revisited Through New Bioinformatic Approaches"],"prefix":"10.3390","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2219-5887","authenticated-orcid":false,"given":"Susana","family":"Valente","sequence":"first","affiliation":[{"name":"Centro de Gen\u00e9tica Preditiva e Preventiva (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Mariana","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica Preditiva e Preventiva (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Jennifer","family":"Schnur","sequence":"additional","affiliation":[{"name":"Lucy Family Institute for Data and Society, University of Notre Dame, Notre Dame, IN 46556, USA"}]},{"given":"Filipe","family":"Alves","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica Preditiva e Preventiva (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Nuno","family":"Moniz","sequence":"additional","affiliation":[{"name":"Lucy Family Institute for Data and Society, University of Notre Dame, Notre Dame, IN 46556, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9746-4412","authenticated-orcid":false,"given":"Dominik","family":"Seelow","sequence":"additional","affiliation":[{"name":"Exploratory Diagnostic Sciences, Berliner Institut F\u00fcr Gesundheitsforschung@Charit\u00e9, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Institut F\u00fcr Medizinische Genetik und Humangenetik, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-6267","authenticated-orcid":false,"given":"Jo\u00e3o Parente","family":"Freixo","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica Preditiva e Preventiva (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-8783","authenticated-orcid":false,"given":"Paulo Filipe","family":"Silva","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica Preditiva e Preventiva (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-6385","authenticated-orcid":false,"given":"Jorge","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica Preditiva e Preventiva (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Laboratory of Cell Biology, Department of Microscopy, ICBAS\u2014Institute of Biomedical Sciences Abel Salazar; Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS\/ITR-Laboratory for Integrative and Translational Research in Population Health, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref_1","first-page":"268","article-title":"Evaluating runs of homozygosity in exome sequencing data\u2014Utility in disease inheritance model selection and variant filtering","volume":"881","author":"Oliveira","year":"2018","journal-title":"Commun. Comput. Inf. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/age.12526","article-title":"Runs of homozygosity: Current knowledge and applications in livestock","volume":"48","author":"Peripolli","year":"2017","journal-title":"Anim. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1093\/bioinformatics\/btu401","article-title":"H3M2: Detection of runs of homozygosity from whole-exome sequencing data","volume":"30","author":"Magi","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejogrb.2018.10.042","article-title":"A review of the reproductive consequences of consanguinity","volume":"232","author":"Oniya","year":"2019","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Marchi, N., Mennecier, P., Georges, M., Lafosse, S., Hegay, T., Dorzhu, C., Chichlo, B., S\u00e9gurel, L., and Heyer, E. (2018). Close inbreeding and low genetic diversity in Inner Asian human populations despite geographical exogamy. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-27047-3"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1038\/s41467-019-11724-6","article-title":"Extreme inbreeding in a European ancestry sample from the contemporary UK population","volume":"10","author":"Yengo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1086\/423146","article-title":"A Population-Genetic Test of Founder Effects and Implications for Ashkenazi Jewish Diseases","volume":"75","author":"Slatkin","year":"2004","journal-title":"Am. J. Hum. Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1023\/A:1015575125780","article-title":"Chromosomal deletions and tumor suppressor genes in prostate cancer","volume":"20","author":"Dong","year":"2001","journal-title":"Cancer Metastasis Rev."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nalls, M.A., Simon-Sanchez, J., Gibbs, J.R., Paisan-Ruiz, C., Bras, J.T., Tanaka, T., Matarin, M., Scholz, S., Weitz, C., and Harris, T.B. (2009). Measures of autozygosity in decline: Globalization, urbanization, and its implications for medical genetics. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000415"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1007\/s00439-019-02045-1","article-title":"Runs of homozygosity in sub-Saharan African populations provide insights into complex demographic histories","volume":"138","author":"Ceballos","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lemes, R.B., Nunes, K., Carnavalli, J.E.P., Kimura, L., Mingroni-Netto, R.C., Meyer, D., and Otto, P.A. (2018). Inbreeding estimates in human populations: Applying new approaches to an admixed Brazilian isolate. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196360"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/ahg.12131","article-title":"Estimation of Recent and Ancient Inbreeding in a Small Endogamous Tunisian Community Through Genomic Runs of Homozygosity","volume":"79","author":"Nagara","year":"2015","journal-title":"Ann. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000478897","article-title":"Consanguinity Rates Predict Long Runs of Homozygosity in Jewish Populations","volume":"82","author":"Kang","year":"2017","journal-title":"Hum. Hered."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ajhg.2012.06.014","article-title":"Genomic patterns of homozygosity in worldwide human populations","volume":"91","author":"Pemberton","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kirin, M., Mcquillan, R., Franklin, C.S., Campbell, H., and Mckeigue, P.M. (2010). Genomic Runs of Homozygosity Record Population History and Consanguinity. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013996"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ajhg.2010.05.018","article-title":"Population genetic structure of the people of Qatar","volume":"87","author":"Musharoff","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mezzavilla, M., Cocca, M., Maisano Delser, P., Badii, R., Abbaszadeh, F., Hadi, K.A., Giorgia, G., and Gasparini, P. (2022). Ancestry-related distribution of Runs of homozygosity and functional variants in Qatari population. BMC Genom. Data, 23.","DOI":"10.1186\/s12863-022-01087-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/ng.3592","article-title":"Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery","volume":"48","author":"Scott","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/jhg.2014.81","article-title":"The influence of admixture and consanguinity on population genetic diversity in Middle East","volume":"59","author":"Yang","year":"2014","journal-title":"J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1016\/j.cub.2021.06.027","article-title":"Human inbreeding has decreased in time through the Holocene","volume":"31","author":"Ceballos","year":"2021","journal-title":"Curr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2026076118","DOI":"10.1073\/pnas.2026076118","article-title":"The genetic structure of the Turkish population reveals high levels of variation and admixture","volume":"118","author":"Kars","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1177\/1352458514557305","article-title":"High inbreeding in the Faroe Islands does not appear to constitute a risk factor for multiple sclerosis","volume":"21","author":"Binzer","year":"2015","journal-title":"Mult. Scler."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/ejhg.2014.299","article-title":"Extensive genome-wide autozygosity in the population isolates of Daghestan","volume":"23","author":"Karafet","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ygeno.2015.01.002","article-title":"Homozygosity mapping in an Irish ALS case-control cohort describes local demographic phenomena and points towards potential recessive risk loci","volume":"105","author":"McLaughlin","year":"2015","journal-title":"Genomics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/cge.12872","article-title":"Chromosomal microarray in a highly consanguineous population: Diagnostic yield, utility of regions of homozygosity, and novel mutations","volume":"91","author":"Alabdullatif","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/ejhg.2014.153","article-title":"Regions of homozygosity identified by oligonucleotide SNP arrays: Evaluating the incidence and clinical utility","volume":"23","author":"Wang","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Prasad, A., Sdano, M.A., Vanzo, R.J., Mowery-Rushton, P.A., Serrano, M.A., Hensel, C.H., and Wassman, E.R. (2018). Clinical utility of exome sequencing in individuals with large homozygous regions detected by chromosomal microarray analysis. BMC Med. Genet., 19.","DOI":"10.1186\/s12881-018-0555-3"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/s41431-020-0609-9","article-title":"First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery","volume":"28","author":"Hengel","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1007\/s00439-020-02187-7","article-title":"Autozygosity-driven genetic diagnosis in consanguineous families from Italy and the Greater Middle East","volume":"139","author":"Palombo","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.mcp.2015.05.008","article-title":"Syndromic ciliopathies: From single gene to multi gene analysis by SNP arrays and next generation sequencing","volume":"29","author":"Knopp","year":"2015","journal-title":"Mol. Cell. Probes"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"de Farias, A.A., Nunes, K., Lemes, R.B., Moura, R., Fernandes, G.R., Melo, U.S., Zatz, M., Kok, F., and Santos, S. (2018). Origin and age of the causative mutations in KLC2, IMPA1, MED25 and WNT7A unravelled through Brazilian admixed populations. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-35022-1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.gene.2013.11.043","article-title":"Infantile-onset ascending hereditary spastic paraplegia with bulbar involvement due to the novel ALS2 mutation c.2761C>T","volume":"536","author":"Wakil","year":"2014","journal-title":"Gene"},{"key":"ref_33","first-page":"59","article-title":"A homozygous mutation in GPT2 associated with nonsyndromic intellectual disability in a consanguineous family from costa rica","volume":"36","author":"Sticht","year":"2017","journal-title":"JIMD Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Guo, T., Tan, Z.P., Chen, H.M., Zheng, D.Y., Liu, L., Huang, X.G., Chen, P., Luo, H., and Yang, Y.F. (2017). An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-08510-z"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1684\/epd.2019.1100","article-title":"Epileptic encephalopathy with microcephaly in a patient with asparagine synthetase deficiency: A video-EEG report","volume":"21","author":"Costa","year":"2019","journal-title":"Epileptic Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1080\/13816810.2019.1709124","article-title":"A founder RDH5 splice site mutation leads to retinitis punctata albescens in two inbred Pakistani kindreds","volume":"41","author":"Khan","year":"2020","journal-title":"Ophthalmic Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jns.2015.10.057","article-title":"Microarray analysis unmasked two siblings with pure hereditary spastic paraplegia shared a run of homozygosity region on chromosome 3q28-q29","volume":"359","author":"Yu","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12110-017-9305-z","article-title":"Inbreeding in Southeastern Spain: The Impact of Geography and Demography on Marital Mobility and Marital Distance Patterns (1900\u20131969)","volume":"29","author":"Masciarelli","year":"2018","journal-title":"Hum. Nat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1159\/000362412","article-title":"Detection of runs of homozygosity from whole exome sequencing data: State of the art and perspectives for clinical, population and epidemiological studies","volume":"77","author":"Pippucci","year":"2014","journal-title":"Hum. Hered."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1126\/science.2884728","article-title":"Homozygosity Mapping: A Way to Map Human Recessive Traits with the DNA of Inbred Children","volume":"236","author":"Lander","year":"1987","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.humimm.2021.02.012","article-title":"Next-generation sequencing technologies: An overview","volume":"82","author":"Hu","year":"2021","journal-title":"Hum. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Pereira, R., Oliveira, J., and Sousa, M. (2020). Bioinformatics and computational tools for next-generation sequencing analysis in clinical genetics. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010132"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Thompson, J.F., and Milos, P.M. (2011). The properties and applications of single-molecule DNA sequencing. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-2-217"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.gpb.2015.08.002","article-title":"PacBio Sequencing and Its Applications","volume":"13","author":"Rhoads","year":"2015","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhang, L., Chen, F.X., Zeng, Z., Xu, M., Sun, F., Yang, L., Bi, X., Lin, Y., Gao, Y.J., and Hao, H.X. (2015). Advances in Metagenomics and Its Application in Environmental Microorganisms. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.766364"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4","DOI":"10.20892\/j.issn.2095-3941.2018.0055","article-title":"Next-generation sequencing and its clinical application","volume":"16","author":"Qin","year":"2019","journal-title":"Cancer Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Barbitoff, Y.A., Polev, D.E., Glotov, A.S., Serebryakova, E.A., Shcherbakova, I.V., Kiselev, A.M., Kostareva, A.A., Glotov, O.S., and Predeus, A.V. (2020). Systematic dissection of biases in whole-exome and whole-genome sequencing reveals major determinants of coding sequence coverage. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-59026-y"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19096","DOI":"10.1073\/pnas.0910672106","article-title":"Genetic diagnosis by whole exome capture and massively parallel DNA sequencing","volume":"106","author":"Choi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bartha, \u00c1., and Gy\u0151rffy, B. (2019). Comprehensive outline of whole exome sequencing data analysis tools available in clinical oncology. Cancers, 11.","DOI":"10.3390\/cancers11111725"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s11910-015-0584-7","article-title":"Axons to Exons: The Molecular Diagnosis of Rare Neurological Diseases by Next-Generation Sequencing","volume":"15","author":"Beaulieu","year":"2015","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"D1333","DOI":"10.1093\/nar\/gkad1005","article-title":"The Human Phenotype Ontology in 2024: Phenotypes around the world","volume":"52","author":"Gargano","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.jmoldx.2022.02.003","article-title":"Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases","volume":"24","author":"Bullich","year":"2022","journal-title":"J. Mol. Diagn."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.jmoldx.2020.06.008","article-title":"Improved Diagnosis of Rare Disease Patients through Systematic Detection of Runs of Homozygosity","volume":"22","author":"Matalonga","year":"2020","journal-title":"J. Mol. Diagn."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ajhg.2011.01.015","article-title":"Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta","volume":"88","author":"Becker","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000371387","article-title":"Increased rate of deleterious variants in long runs of homozygosity of an inbred population from Qatar","volume":"79","author":"Mezzavilla","year":"2015","journal-title":"Hum. Hered."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3777","DOI":"10.1210\/jc.2009-1715","article-title":"Runs of homozygosity identify a recessive locus 12q21.31 for human adult height","volume":"95","author":"Yang","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wang, L.S., Hranilovic, D., Wang, K., Lindquist, I.E., Yurcaba, L., Petkovic, Z.B., Gidaya, N., Jernej, B., Hakonarson, H., and Bucan, M. (2010). Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia. BMC Med. Genet., 11.","DOI":"10.1186\/1471-2350-11-134"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gross, A., T\u00f6njes, A., Kovacs, P., Veeramah, K.R., Ahnert, P., Roshyara, N.R., Gieger, C., Rueckert, I.M., Loeffler, M., and Stoneking, M. (2011). Population-genetic comparison of the Sorbian isolate population in Germany with the German KORA population using genome-wide SNP arrays. BMC Genet., 12.","DOI":"10.1186\/1471-2156-12-67"},{"key":"ref_59","first-page":"1261","article-title":"Evidence of recessive Alzheimer disease loci in a Caribbean Hispanic data set: Genome-wide survey of runs of homozygosity","volume":"70","author":"Ghani","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1002\/jbmr.2558","article-title":"Genome-wide Survey of Runs of Homozygosity Identifies Recessive Loci for Bone Mineral Density in Caucasian and Chinese Populations","volume":"30","author":"Yang","year":"2015","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1001\/jamaneurol.2015.1700","article-title":"Association of Long Runs of Homozygosity with Alzheimer Disease Among African American Individuals","volume":"72","author":"Ghani","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"213.e3","DOI":"10.1016\/j.neurobiolaging.2016.06.001","article-title":"Genome-wide assessment of Parkinson\u2019s disease in a Southern Spanish population","volume":"45","author":"Price","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1093\/molbev\/msz174","article-title":"The Current Genomic Landscape of Western South America: Andes, Amazonia, and Pacific Coast","volume":"36","author":"Barbieri","year":"2019","journal-title":"Mol. Biol. Evol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1093\/molbev\/msab070","article-title":"The Counteracting Effects of Demography on Functional Genomic Variation: The Roma Paradigm","volume":"38","author":"Lopez","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"jkac111","DOI":"10.1093\/g3journal\/jkac111","article-title":"Demographic history differences between Hispanics and Brazilians imprint haplotype features","volume":"12","author":"Ananina","year":"2022","journal-title":"G3"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Ruan, X., Kocher, J.P.A., Pommier, Y., Liu, H., and Reinhold, W.C. (2012). Mass homozygotes accumulation in the NCI-60 cancer cell lines as compared to HapMap Trios, and relation to fragile site location. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031628"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Santoni, F.A., Makrythanasis, P., and Antonarakis, S.E. (2015). CATCHing putative causative variants in consanguineous families. BMC Bioinform., 16.","DOI":"10.1186\/s12859-015-0727-5"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5567","DOI":"10.1093\/bioinformatics\/btaa940","article-title":"Obelisc: An identical-by-descent mapping tool based on SNP streak","volume":"36","author":"Sonehara","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1111\/j.1469-8749.2011.03993.x","article-title":"FA2H-related disorders: A novel c.270+3A>T splice-site mutation leads to a complex neurodegenerative phenotype","volume":"53","author":"Garone","year":"2011","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"W516","DOI":"10.1093\/nar\/gks487","article-title":"HomozygosityMapper2012-bridging the gap between homozygosity mapping and deep sequencing","volume":"40","author":"Seelow","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"W593","DOI":"10.1093\/nar\/gkp369","article-title":"HomozygosityMapper\u2014An interactive approach to homozygosity mapping","volume":"37","author":"Seelow","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/gim.2015.139","article-title":"Novel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing","volume":"18","author":"Kancheva","year":"2016","journal-title":"Genet. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1093\/bioinformatics\/btx102","article-title":"GARLIC: Genomic Autozygosity Regions Likelihood-based Inference and Classification","volume":"33","author":"Szpiech","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/bioinformatics\/btt686","article-title":"HomSI: A homozygous stretch identifier from next-generation sequencing data","volume":"30","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41467-020-20584-4","article-title":"AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data","volume":"12","author":"Quinodoz","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"402","DOI":"10.2174\/138920209789177575","article-title":"Hidden Markov Models and their Applications in Biological Sequence Analysis","volume":"10","author":"Yoon","year":"2009","journal-title":"Curr. Genom."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1093\/bioinformatics\/btw044","article-title":"BCFtools\/RoH: A hidden Markov model approach for detecting autozygosity from next-generation sequencing data","volume":"32","author":"Narasimhan","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zhuang, Z., Gusev, A., Cho, J., and Pe\u2019er, I. (2012). Detecting Identity by Descent and Homozygosity Mapping in Whole-Exome Sequencing Data. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047618"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.ajhg.2010.02.021","article-title":"High-Resolution Detection of Identity by Descent in Unrelated Individuals","volume":"86","author":"Browning","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/humu.24316","article-title":"ROHMM\u2014A flexible hidden Markov model framework to detect runs of homozygosity from genotyping data","volume":"43","year":"2022","journal-title":"Hum. Mutat."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1093\/bioinformatics\/btw046","article-title":"FILTUS: A desktop GUI for fast and efficient detection of disease-causing variants, including a novel autozygosity detector","volume":"32","author":"Vigeland","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_82","unstructured":"(2023, June 06). hapROH \u00b7 PyPI. (n.d.). Retrieved 27 March 2023. Available online: https:\/\/pypi.org\/project\/hapROH\/."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1038\/s41467-021-25289-w","article-title":"Parental relatedness through time revealed by runs of homozygosity in ancient DNA","volume":"12","author":"Ringbauer","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02289565","article-title":"Multidimensional scaling by optimizing goodness of fit to a nonmetric hypothesis","volume":"29","author":"Kruskal","year":"1964","journal-title":"Psychometrika"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1080\/00401706.1999.10485670","article-title":"A fast algorithm for the minimum covariance determinant estimator","volume":"41","author":"Rousseeuw","year":"1999","journal-title":"Technometrics"},{"key":"ref_86","first-page":"342","article-title":"Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1)","volume":"60","author":"Lalioti","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ajhg.2008.08.007","article-title":"Runs of Homozygosity in European Populations","volume":"83","author":"McQuillan","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41398-020-01145-1","article-title":"Long runs of homozygosity are associated with Alzheimer\u2019s disease","volume":"11","author":"Farias","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_89","first-page":"41","article-title":"Sum\u00e1rio 41 Incid\u00eancia de Casamentos Consangu\u00edneos na Popula\u00e7\u00e3o Incid\u00eancia de Casamentos Consangu\u00edneos na Popula\u00e7\u00e3o Portuguesa-1980\u20131986","volume":"Volume 3","author":"Santos","year":"1988","journal-title":"Sa\u00fade em N\u00fameros"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nrg.2017.109","article-title":"Runs of homozygosity: Windows into population history and trait architecture","volume":"19","author":"Ceballos","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/s41588-019-0528-2","article-title":"PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels","volume":"51","author":"Martin","year":"2019","journal-title":"Nat. Genet."}],"container-title":["BioMedInformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-7426\/4\/4\/128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:52:55Z","timestamp":1760115175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-7426\/4\/4\/128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":91,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["biomedinformatics4040128"],"URL":"https:\/\/doi.org\/10.3390\/biomedinformatics4040128","relation":{},"ISSN":["2673-7426"],"issn-type":[{"type":"electronic","value":"2673-7426"}],"subject":[],"published":{"date-parts":[[2024,12,16]]}}}