{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:06:39Z","timestamp":1772168799255,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.10937.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T00:00:00Z","timestamp":1507507200000}}],"reference-count":26,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T00:00:00Z","timestamp":1507507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Introduction<\/ns4:bold>\n                    : Lymphedema is an abnormal accumulation of interstitial fluid, due to inefficient uptake and reduced flow, leading to swelling and disability, mostly in the extremities. Hereditary lymphedema usually occurs as an autosomal dominant trait with allelic heterogeneity.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods<\/ns4:bold>\n                    : We identified single nucleotide polymorphisms (SNPs) in the FOXC2 gene using dbSNP, analyzed their effect on the resulting protein using VEP and Biomart, modelled the resulting protein using Project HOPE, identified gene \u2013 gene interactions using GeneMANIA and predicted miRNAs affected and the resulting effects of SNPs in the 5\u2019 and 3\u2019 regions using PolymiRTS.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results<\/ns4:bold>\n                    : We identified 473 SNPs - 429 were nsSNPs and 44 SNPs were in the 5\u2019 and 3\u2019 UTRs. In total, 2 SNPs - rs121909106 and rs121909107 - have deleterious effects on the resulting protein, and a 3D model confirmed those effects. The gene \u2013 gene interaction network showed the involvement of FOXC2 protein in the development of the lymphatic system. hsa-miR-6886-5p, hsa-miRS-6886-5p, hsa-miR-6720-3p, which were affected by the SNPs rs201118690, rs6413505, rs201914560, respectively, were the most important miRNAs affected, due to their high conservation score.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions<\/ns4:bold>\n                    : rs121909106 and rs121909107 were predicted to have the most harmful effects, while hsa-miR-6886-5p, hsa-miR-6886-5p and hsa-miR-6720-3p were predicted to be the most important miRNAs affected. Computational biology tools have advantages and disadvantages, and the results they provide are predictions that require confirmation using methods such as functional studies.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.10937.2","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T09:35:27Z","timestamp":1507541727000},"page":"243","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["In silico analysis of single nucleotide polymorphisms (SNPs) in human FOXC2 gene"],"prefix":"10.12688","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9409-6685","authenticated-orcid":false,"given":"Mohammed","family":"Nimir","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-9338","authenticated-orcid":false,"given":"Mohanad","family":"Abdelrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0987-4172","authenticated-orcid":false,"given":"Mohamed","family":"Abdelrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahil","family":"Abdalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wala eldin","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhanned","family":"Abdullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6157-4388","authenticated-orcid":false,"given":"Muzamil Mahdi Abdel","family":"Hamid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2017,10,9]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"54-63","DOI":"10.1038\/scientificamerican1081-54","article-title":"The patient record in epidemiology.","volume":"245","author":"L Kurland","year":"1981","journal-title":"Sci Am."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"153-9","DOI":"10.1038\/75997","article-title":"Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema.","volume":"25","author":"M 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.13959.r26810, Pascal Brouillard, Laboratory of Human Molecular Genetics, de Duve Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium, 15 Feb 2018, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/6-243\/v2#referee-response-26810","order":0,"name":"referee-response-26810","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.13959.r26811, Fengkai Zhang, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA, 30 Oct 2017, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/6-243\/v2#referee-response-26811","order":1,"name":"referee-response-26811","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}