{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:35:51Z","timestamp":1787884551896,"version":"build-2784847793"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hereditary sensory and autonomic neuropathies (HSAN) represent a group of genetic diseases affecting the peripheral nervous system. In humans, at least 16 loci have been associated with the disorder but do not explain the disease origin of all patients. In dogs, similar conditions have been documented for decades in various breeds with a severe impact on life quality and are often referred to as acral mutilation syndrome (AMS). Causal variants in three genes have been identified to date, suggesting larger genetic heterogeneity in the dog population. Our aim was to explain the genetic etiology of an early\u2010onset HSAN\/AMS in a purebred German Spitz. The affected dog showed progressive loss of pain sensation in the distal extremities, which led to intense licking, biting, and self\u2010mutilation of digits and paw pads. Whole\u2010genome sequencing identified a single candidate causal variant on chromosome 4 in the <jats:italic>RETREG1<\/jats:italic> gene (c.656C&gt;T, p.Pro219Leu). This missense variant was previously recognized as deleterious in a mixed breed dog family with similar clinical signs. Haplotype analyses and targeted genotyping revealed a likely German Spitz ancestry of these mixed breed dogs. Further screening of an extensive cohort of ~900\u2009000 dogs of various breeds hinted at the variant allele origin in the German Spitz breed. Disruption of RETREG1 inhibits endoplasmic reticulum turnover and leads to neuron degeneration. Our findings provide evidence that this variant underlies the recessive form of HSAN\/AMS in the German Spitz and support the use of whole\u2010genome sequencing\u2010based veterinary precision medicine for early diagnosis and prevention via a genetic test.<\/jats:p>","DOI":"10.1111\/age.13482","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T17:04:41Z","timestamp":1728407081000},"page":"810-819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A <i>RETREG1<\/i> variant is associated with hereditary sensory and autonomic neuropathy with acral self\u2010mutilation in purebred German Spitz"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6521-1285","authenticated-orcid":false,"given":"Anna","family":"Letko","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR) \u2013 UMR6290, CNRS Universit\u00e9 de Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7769-8978","authenticated-orcid":false,"given":"Pascale","family":"Quignon","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR) \u2013 UMR6290, CNRS Universit\u00e9 de Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1395-9582","authenticated-orcid":false,"given":"Ma\u00e9va","family":"Quiller\u00e9","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR) \u2013 UMR6290, CNRS Universit\u00e9 de Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Charles","family":"Husson","sequence":"additional","affiliation":[{"name":"Laboratoire d'Anatomie Pathologique V\u00e9t\u00e9rinaire (LAPVSO)  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6968-3864","authenticated-orcid":false,"given":"Caroline Dufaure","family":"de Citres","sequence":"additional","affiliation":[{"name":"ANTAGENE \u2013 Animal Genomics Laboratory  La Tour de Salvagny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9874-8484","authenticated-orcid":false,"given":"Jonas","family":"Donner","sequence":"additional","affiliation":[{"name":"Wisdom Panel, Mars Petcare Science &amp; Diagnostics  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Dr\u00e9ano","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR) \u2013 UMR6290, CNRS Universit\u00e9 de Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-1595","authenticated-orcid":false,"given":"Jocelyn","family":"Plassais","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR) \u2013 UMR6290, CNRS Universit\u00e9 de Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8590-2174","authenticated-orcid":false,"given":"Catherine","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR) \u2013 UMR6290, CNRS Universit\u00e9 de Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/JVIM.15312"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.17180\/novae\u20102022\u2010NS02\u2010art05"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1534\/GENETICS.113.150029"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/JNS.12581"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTY560"},{"key":"e_1_2_9_7_1","first-page":"289","volume-title":"Methods in molecular biology","author":"Cingolani P.","year":"2022"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvsm.2004.05.011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010011\u20106397\u2010y"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007361"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010651"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/GR.8.3.186"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/GR.8.3.175"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.116.027896"},{"key":"e_1_2_9_16_1","unstructured":"Garrigan D. Huff J.&Foran R.C.(2024)BCSYS: An Accurate and Scalable Local Ancestry Classifier.https:\/\/www.wisdompanel.com\/downloads\/wp\u2010breed\u2010detection.pdf(Accessed 2 May 2024)"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.BI1102S02"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2010.06.003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.16610"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/JVIM.16242"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAA1028"},{"key":"e_1_2_9_22_1","unstructured":". (2023)DEUTSCHER SPITZ.https:\/\/fci.be\/en\/nomenclature\/GERMAN\u2010SPITZ\u201097.html(Accessed 14 August 2023)"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/MUS.24145"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12834"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019102608"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/GR.229102"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.464"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010animal\u2010050622\u2010055534"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010022\u201000365\u20107"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.079"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PGEN.1006482"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/201178"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_9_34_1","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2019"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41597\u2010023\u201002166\u20103"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbs017"},{"key":"e_1_2_9_37_1","volume-title":"Genomics in the cloud: using docker, GATK, and WDL in Terra","author":"Van der Auwera G.A.","year":"2020"},{"key":"e_1_2_9_38_1","first-page":"314","volume-title":"Proceedings \u2013 2019 IEEE 33rd international parallel and distributed processing symposium","author":"Vasimuddin M.","year":"2019"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/S42003\u2010021\u201001698\u2010X"}],"container-title":["Animal Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/age.13482","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T10:21:56Z","timestamp":1730715716000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/age.13482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/age.13482"],"URL":"https:\/\/doi.org\/10.1111\/age.13482","archive":["Portico"],"relation":{},"ISSN":["0268-9146","1365-2052"],"issn-type":[{"value":"0268-9146","type":"print"},{"value":"1365-2052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,8]]},"assertion":[{"value":"2024-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}