{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:13:56Z","timestamp":1791893636282,"version":"4.3.4"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T00:00:00Z","timestamp":1696032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The GDF5 gene is involved in the development of skeletal elements, synovial joint formation, tendons, ligaments, and cartilage. Several polymorphisms are present within the gene, and two of them, rs143384 and 143383, were reported to be correlated with osteoarticular disease or muscle flexibility. The aim of this research is to verify if the worldwide distribution of the rs143384 polymorphism among human populations was shaped by selective pressure, or if it was the result of random genetic drift events. Ninety-four individuals of both the male and female sexes, 18\u201328 years old, from Sardinia were analyzed. We observed the following genotype frequencies: 28.72% of AA homozygotes, 13.83% of GG homozygotes, and 57.45% of AG heterozygotes. The allele frequencies were 0.574 for allele A and 0.426 for allele G. The relationships between the populations were verified via Multidimensional Scaling (MDS). Our data show (i) a clear heterogeneity within the African populations; (ii) a strong differentiation between the African populations and the other populations; and that (iii) the Sardinian population is placed within the European cluster. To reveal possible traces of selective pressure, the Population Branch Statistic (PBS) was calculated; both the rs143384 and 143383 SNPs have low PBS values, suggesting that there are no signals of selective pressure in those areas of the gene.<\/jats:p>","DOI":"10.3390\/genes14101895","type":"journal-article","created":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T16:58:09Z","timestamp":1696179489000},"page":"1895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Influence of Different Evolutive Forces on GDF5 Gene Variability"],"prefix":"10.3390","volume":"14","author":[{"given":"Laura","family":"Flore","sequence":"first","affiliation":[{"name":"Department of Life and Environment Sciences, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7912-162X","authenticated-orcid":false,"given":"Paolo","family":"Francalacci","sequence":"additional","affiliation":[{"name":"Department of Life and Environment Sciences, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myosotis","family":"Massidda","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0661-9309","authenticated-orcid":false,"given":"Renato","family":"Robledo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Maria","family":"Cal\u00f2","sequence":"additional","affiliation":[{"name":"Department of Life and Environment Sciences, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1469-7580.2005.00447.x","article-title":"The role of growth\/differentiation factor 5 (GDF5) in the induction and survival of midbrain dopaminergic neurons: Relevance to Parkinson\u2019s disease treatment","volume":"207","author":"Sullivan","year":"2005","journal-title":"J. Anat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/368639a0","article-title":"Limb alterations in brachypodism mice due to mutations in a new member of the TGF \u03b2-superfamily","volume":"368","author":"Storm","year":"1994","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1242\/dev.126.6.1305","article-title":"Mechanisms of GDF-5 action during skeletal development","volume":"126","author":"Abdelfattah","year":"1999","journal-title":"Development"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1006\/excr.1999.4535","article-title":"p38 mitogen-activated protein kinase functionally contributes to chondrogenesis induced by growth\/differentiation factor-5 in ATDC5 cells","volume":"250","author":"Nakamura","year":"1999","journal-title":"Exp. Cell Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.2106\/00004623-200100001-00004","article-title":"Growth\/differentiation factor-5 (GDF-5) and skeletal development","volume":"83","author":"Buxton","year":"2001","journal-title":"J. Bone Joint Surg. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/bdrc.10015","article-title":"Development of synovial joints","volume":"69","author":"Archer","year":"2003","journal-title":"Birth Defects Res. C. Embryo Today"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1186\/s13018-021-02549-5","article-title":"The effect of common variants in GDF5 gene on the susceptibility to chronic postsurgical pain","volume":"16","author":"Yan","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/ng0997-58","article-title":"Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1","volume":"17","author":"Thomas","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ng0997-18","article-title":"Mutations in CDMP1 cause autosomal dominant brachydactyly type C","volume":"17","author":"Polinkovsky","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/art.39932","article-title":"Genome-Wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians","volume":"69","author":"Yau","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_11","unstructured":"Naureen, Z., Lorusso, L., Manganotti, P., Caruso, P., Mazzon, G., Cecchin, S., Marceddu, G., and Bertelli, M. (2020). Genetics of pain: From rare Mendelian disorders to genetic predisposition to pain. Acta Biomed., 91."},{"key":"ref_12","unstructured":"WHO Scientific Group on the Burden of Musculoskeletal Conditions at the Start of the New Millennium (2003). The Burden of Musculoskeletal Conditions at the Start of the New Millennium, WHO. World Health Organization Technical Report Series."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1093\/hmg\/ddr253","article-title":"Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation","volume":"20","author":"Reynard","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1080\/03008200600980769","article-title":"Recombinant growth\/differentiation factor-5 stimulates osteogenic differentiation of fat-derived stromal cells in vitro","volume":"47","author":"Zeng","year":"2006","journal-title":"Connect. Tissue Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/BOR.0000000000000171","article-title":"Genetic contribution to osteoarthritis development: Current state of evidence","volume":"27","author":"Loughlin","year":"2015","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/2005","article-title":"A functional polymorphism in the 5\u2032 UTR of GDF5 is associated with susceptibility to osteoarthritis","volume":"39","author":"Miyamoto","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s13075-020-02306-9","article-title":"Association between growth differentiation factor 5 rs143383 genetic polymorphism and the risk of knee osteoarthritis among Caucasian but not Asian: A meta-analysis","volume":"22","author":"Peng","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1177\/0300060516639751","article-title":"Prospective cohort study of the risk factors for stress fractures in Chinese male infantry recruits","volume":"44","author":"Zhao","year":"2016","journal-title":"J. Int. Med. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1519\/JSC.0000000000003142","article-title":"Effect of COL5A1, GDF5, and PPARA Genes on a Movement Screen and Neuromuscular Performance in Adolescent Team Sport Athletes","volume":"33","author":"Stastny","year":"2019","journal-title":"J. Strength Cond. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Meng, W., Adams, M.J., Palmer, C.N., Shi, J., Auton, A., Ryan, K.A., Jordan, J.M., Mitchell, B.D., Jackson, R.D., and Yau, M.S. (2019). Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank. Commun. Biol., 2.","DOI":"10.1038\/s42003-019-0568-2"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.joca.2010.05.018","article-title":"Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population","volume":"18","author":"Rouault","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1093\/genetics\/105.3.767","article-title":"Estimation of the coancestry coefficient: Basis for a short-term genetic distance","volume":"105","author":"Reynolds","year":"1983","journal-title":"Genetics"},{"key":"ref_23","unstructured":"R Core Team (2021). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1093\/bioinformatics\/btr330","article-title":"1000 Genomes Project Analysis Group. The variant call format and VCFtools","volume":"27","author":"Danecek","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1126\/science.1190371","article-title":"Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude","volume":"329","author":"Yi","year":"2010","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/325031a0","article-title":"Mitochondrial DNA and human evolution","volume":"325","author":"Cann","year":"1987","journal-title":"Nature"},{"key":"ref_27","unstructured":"Cavalli-Sforza, L.L., Menozzi, P., and Piazza, A. (1994). The History and Geography of Human Genes, Princeton University Press."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/03014460.2021.1944312","article-title":"From old markers to next generation: Reconstructing the history of the peopling of Sardinia","volume":"48","author":"Vona","year":"2021","journal-title":"Ann. Hum. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/ng.78","article-title":"Natural selection has driven population differentiation in modern humans","volume":"40","author":"Barreiro","year":"2008","journal-title":"Nat. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/10\/1895\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:02:37Z","timestamp":1760130157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/10\/1895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,30]]},"references-count":29,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["genes14101895"],"URL":"https:\/\/doi.org\/10.3390\/genes14101895","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,30]]}}}