{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:17:28Z","timestamp":1760239048179,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["DISL_RILO_16_01"],"award-info":[{"award-number":["DISL_RILO_16_01"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Arthrogryposis and macroglossia are congenital pathologies known in several cattle breeds, including Piemontese. As variations in single genes were identified as responsible for arthrogryposis in some breeds, we decided: (i) to test the hypothesis of a similar genetic determinism for arthrogryposis in the Piemontese breed by genotyping affected and healthy animals with a high-density chip and applying genome-wide association study (GWAS), FST and canonical discriminant analysis (CDA) procedures, and (ii) to investigate with the same approach the genetic background of macroglossia, for which no genetic studies exist so far. The study included 125 animals (63 healthy, 30 with arthrogryposis, and 32 with macroglossia). Differently from what reported for other breeds, the analysis did not evidence a single strong association with the two pathologies. Rather, 23 significant markers on different chromosomes were found (7 associated to arthrogryposis, 11 to macroglossia, and 5 to both pathologies), suggesting a multifactorial genetic mechanism underlying both diseases in the Piemontese breed. In the 100-kb interval surrounding the significant SNPs, 20 and 26 genes were identified for arthrogryposis and macroglossia, respectively, with 12 genes in common to both diseases. For some genes (NTN3, KCNH1, KCNH2, and KANK3), a possible role in the pathologies can be hypothesized, being involved in processes related to muscular or nervous tissue development. The real involvement of these genes needs to be further investigated and validated.<\/jats:p>","DOI":"10.3390\/ani10101732","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T04:18:57Z","timestamp":1600921137000},"page":"1732","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetics of Arthrogryposis and Macroglossia in Piemontese Cattle Breed"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4797-2897","authenticated-orcid":false,"given":"Liliana","family":"Di Stasio","sequence":"first","affiliation":[{"name":"Department of Agricultural, Forest and Food Sciences, University of Torino, Largo Baccini 2, 10095 Grugliasco (TO), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Albera","sequence":"additional","affiliation":[{"name":"Associazione Nazionale Allevatori Bovini di Razza Piemontese, strada provinciale Trinita\u2019 31\/A, 12061 Carr\u00f9 (CN), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3140-9373","authenticated-orcid":false,"given":"Alfredo","family":"Pauciullo","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Forest and Food Sciences, University of Torino, Largo Baccini 2, 10095 Grugliasco (TO), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4637-8669","authenticated-orcid":false,"given":"Alberto","family":"Cesarani","sequence":"additional","affiliation":[{"name":"Department of Agriculture, University of Sassari, Via De Nicola 9, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicol\u00f2 P. P.","family":"Macciotta","sequence":"additional","affiliation":[{"name":"Department of Agriculture, University of Sassari, Via De Nicola 9, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1604-8917","authenticated-orcid":false,"given":"Giustino","family":"Gaspa","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Forest and Food Sciences, University of Torino, Largo Baccini 2, 10095 Grugliasco (TO), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/oxfordjournals.jhered.a103843","article-title":"A hereditary lethal muscle contracture in cattle","volume":"25","author":"Hutt","year":"1934","journal-title":"J. Hered."},{"key":"ref_2","first-page":"1367","article-title":"Arthrogryposis and associated defects in newborn calves","volume":"31","author":"Leipold","year":"1970","journal-title":"Am. J. Vet. Res."},{"key":"ref_3","first-page":"164","article-title":"Clinical, pathological and other visible traits loci except coat colour (category 2)","volume":"Volume 101","author":"Millar","year":"2000","journal-title":"Mendelian Inheritance in Cattle 2000"},{"key":"ref_4","first-page":"198","article-title":"Lupine, a cause of crooked calf disease","volume":"151","author":"Shupe","year":"1967","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.cvfa.2008.07.008","article-title":"Management of Tendon Disorders in Cattle","volume":"24","author":"Anderson","year":"2008","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_6","first-page":"133","article-title":"\u00c9tude du caract\u00e8re culard. I. Mise au point bibliographique. Annales de zootechnie, INRA\/EDP","volume":"12","author":"Lauvergne","year":"1963","journal-title":"Sciences"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.livsci.2010.02.008","article-title":"Physiological limits to growth and the related effects on meat quality","volume":"130","author":"Webb","year":"2010","journal-title":"Livest. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/15227950600701503","article-title":"\u201cDouble-Muscle\u201d trait in cattle: A possible model for Wiedemann-Beckwith Syndrome","volume":"25","author":"Best","year":"2006","journal-title":"Fetal Pediatr. Pathol."},{"key":"ref_9","unstructured":"Biscarini, F., Del Corvo, M., Stella, A., Alber, A., Ferencakovic, M., and Pollo, G. (2013, January 14\u201315). Busqueda de las mutaciones causales para artrogriposis y macroglosia en vacuno de raza piemontesa: Resultados preliminares. Proceedings of the XV Jornadas sobre Producci\u00f3n Animal, Zaragoza, Spain."},{"key":"ref_10","unstructured":"Beever, J.E., and Marron, B.M. (2011). Screening for Arthrogryposis Multiplex in Bovines. (20,110,151,440 A1), U.S. Patent."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1111\/jvim.13599","article-title":"Genetic abnormalities in a calf with congenital increased muscular tonus","volume":"29","author":"Wiedemar","year":"2015","journal-title":"J. Vet. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s12864-015-1528-y","article-title":"Genome-wide next-generation DNA and RNA sequencing reveals a mutation that perturbs splicing of the phosphatidylinositol glycan anchor biosynthesis class H gene (PIGH) and causes arthrogryposis in Belgian Blue cattle","volume":"16","author":"Sartelet","year":"2015","journal-title":"BMC Genom."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Agerholm, J.S., McEvoy, F.J., Menzi, F., Jagannathan, V., and Dr\u00f6gem\u00fcller, C.A. (2016). CHRNB1 frameshift mutation is associated with familial arthrogryposis multiplex congenita in Red dairy cattle. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2832-x"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chang, C.C., Chow, C.C., Tellier, L.C.A.M., Vattikuti, S., Purcell, S.M., and Lee, J.J. (2015). Second-generation PLINK: Rising to the challenge of larger and richer datasets. GigaScience, 4.","DOI":"10.1186\/s13742-015-0047-8"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ajhg.2015.11.020","article-title":"Genotype imputation with millions of reference samples","volume":"98","author":"Browning","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/age.12409","article-title":"Genome-wide association reveals the locus responsible for four-horned ruminant","volume":"47","author":"Kijas","year":"2016","journal-title":"Anim. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.livsci.2019.05.009","article-title":"A combined genome-wide approach identifies a new potential candidate marker associated with the coat color sidedness in cattle","volume":"225","author":"Mastrangelo","year":"2019","journal-title":"Livest. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. B Methodol."},{"key":"ref_19","first-page":"1358","article-title":"Estimating F-statistics for the analysis of population structure","volume":"38","author":"Weir","year":"1984","journal-title":"Evolution"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12711-016-0236-7","article-title":"Use of canonical discriminant analysis to study signatures of selection in cattle","volume":"48","author":"Sorbolini","year":"2016","journal-title":"Genet. Sel. Evol."},{"key":"ref_21","unstructured":"Zeggini, E., and Morris, A. (2011). Effects of Population Structure in Genome-wide Association Studies in Analysis of complex Disease Association Study. Analysis of Complex Disease Association Studies, Accademic Press. [1st ed.]. Chapter 9."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/ng1847","article-title":"Principal components analysis corrects for stratification in genome-wide association studies","volume":"38","author":"Price","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/mec.15410","article-title":"Combining genome-wide association study and FST-based approaches to identify targets of Borrelia-mediated selection in natural rodent hosts","volume":"29","author":"Cornetti","year":"2020","journal-title":"Mol. Ecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.smallrumres.2019.06.014","article-title":"Investigation of genetic diversity and selection signatures between Sarda and Sardinian Ancestral black, two related sheep breeds with evident morphological differences","volume":"177","author":"Cesarani","year":"2019","journal-title":"Small Rumin. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Manca, E., Cesarani, A., Gaspa, G., Sorbolini, S., Macciotta, N.P., and Dimauro, C. (2020). Use of the Multivariate Discriminant Analysis for Genome-Wide Association Studies in Cattle. Animals, 10.","DOI":"10.3390\/ani10081300"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/j.1751-0813.2011.00826.x","article-title":"Neurological diseases of ruminant livestock in Australia. V: Congenital neurogenetic disorders of cattle","volume":"89","author":"Windsor","year":"2011","journal-title":"Aust. Vet. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/gb-2009-10-9-239","article-title":"The Netrin Protein Family","volume":"10","author":"Sathyanath","year":"2009","journal-title":"Genome Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.1523\/JNEUROSCI.19-12-04938.1999","article-title":"Netrin-3, a Mouse Homolog of Human NTN2L, Is Highly Expressed in Sensory Ganglia and Shows Differential Binding to Netrin Receptors","volume":"19","author":"Wang","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_29","first-page":"304","article-title":"Protein Distribution of Kcnq1, Kcnq2, and Kcnq3 Potassium Channel Subunits during Mouse embryonic Development","volume":"288","author":"Franco","year":"2006","journal-title":"Anat. Rec."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0014-5793(98)00973-9","article-title":"Cloning of a Human Ether-a-Go-Go Potassium Channel Expressed in Myoblasts at the Onset of Fusion","volume":"434","author":"Occhiodoro","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.bbagen.2007.09.017","article-title":"Kank Proteins: A New Family of Ankyrin-Repeat Domain-Containing Proteins","volume":"1780","author":"Zhu","year":"2008","journal-title":"BBA-Gen. Subj."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/10\/10\/1732\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:13:03Z","timestamp":1760177583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/10\/10\/1732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":31,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ani10101732"],"URL":"https:\/\/doi.org\/10.3390\/ani10101732","relation":{},"ISSN":["2076-2615"],"issn-type":[{"type":"electronic","value":"2076-2615"}],"subject":[],"published":{"date-parts":[[2020,9,24]]}}}