{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:08Z","timestamp":1792789448046,"version":"4.5.0"},"reference-count":85,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T00:00:00Z","timestamp":1691280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tel-Aviv University"},{"name":"University Hospital of Regensburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Depending on how severe it is, malocclusion, which may involve misaligned teeth, jaws, or a combination of the two, can hurt a person\u2019s overall facial aesthetics. The maxillary molar develops before the mandibular molar in class II malocclusion, which affects 15% of the population in the United States. With a retrusive mandible, patients typically have a convex profile. The goal of this study is to classify the skeletal and dental variability present in class II malocclusion, to reduce heterogeneity, present the current clinical treatment strategies, to summarize the previously published findings of genetic analysis, discuss these findings and their constraints, and finally, propose a comprehensive roadmap to facilitate investigations aimed at determining the genetic bases of malocclusion development using a variety of genomic approaches. To further comprehend the hereditary components involved in the onset and progression of class II malocclusion, a novel animal model for class II malocclusion should be developed while considering the variety of the human population. To overcome the constraints of the previous studies, here, we propose to conduct novel research on humans with the support of mouse models to produce contentious findings. We believe that carrying out a genome-wide association study (GWAS) on a large human cohort to search for significant genes and their modifiers; an epigenetics-wide association study (EWAS); RNA-seq analysis; integrating GWAS and the expression of quantitative trait loci (eQTL); and the testing of microRNAs, small RNAs, and long noncoding RNAs in tissues related to the skeletal class II malocclusion (SCIIMO) phenotype, such as mandibular bone, gum, and jaw in humans and the collaborative cross (CC) mouse model, will identify novel genes and genetic factors affecting this phenotype. We anticipate discovering novel genetic elements to advance our knowledge of how this malocclusion phenotype develops and open the venue for the early identification of patients carrying the susceptible genetic factors so that we can offer early prevention treatment strategies.<\/jats:p>","DOI":"10.3390\/jcm12155148","type":"journal-article","created":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T10:01:53Z","timestamp":1691316113000},"page":"5148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Skeletal Class II Malocclusion: From Clinical Treatment Strategies to the Roadmap in Identifying the Genetic Bases of Development in Humans with the Support of the Collaborative Cross Mouse Population"],"prefix":"10.3390","volume":"12","author":[{"given":"Iqbal M.","family":"Lone","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3530-1420","authenticated-orcid":false,"given":"Osayd","family":"Zohud","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kareem","family":"Midlej","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Proff","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nezar","family":"Watted","sequence":"additional","affiliation":[{"name":"Center for Dentistry Research and Aesthetics, Jatt 4491800, Israel"},{"name":"Department of Orthodontics, Faculty of Dentistry, Arab America University, Jenin 34567, Palestine"},{"name":"Gathering for Prosperity Initiative, Jatt 4491800, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5525-206X","authenticated-orcid":false,"given":"Fuad A.","family":"Iraqi","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Department of Orthodontics, University Hospital of Regensburg, 93053 Regensburg, Germany"},{"name":"Gathering for Prosperity Initiative, Jatt 4491800, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Guo, L., Feng, Y., Guo, H.G., Liu, B.W., and Zhang, Y. 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