{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:17:43Z","timestamp":1790914663270,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,6]],"date-time":"2024-10-06T00:00:00Z","timestamp":1728172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Recovery and Resilience Plan (NRRP)","award":["CUP H53D23003260006"],"award-info":[{"award-number":["CUP H53D23003260006"]}]},{"name":"National Recovery and Resilience Plan (NRRP)","award":["104"],"award-info":[{"award-number":["104"]}]},{"name":"National Recovery and Resilience Plan (NRRP)","award":["1015"],"award-info":[{"award-number":["1015"]}]},{"name":"European Union\u2014NextGenerationEU","award":["CUP H53D23003260006"],"award-info":[{"award-number":["CUP H53D23003260006"]}]},{"name":"European Union\u2014NextGenerationEU","award":["104"],"award-info":[{"award-number":["104"]}]},{"name":"European Union\u2014NextGenerationEU","award":["1015"],"award-info":[{"award-number":["1015"]}]},{"name":"Italian Ministry of Ministry of University and Research (MUR)","award":["CUP H53D23003260006"],"award-info":[{"award-number":["CUP H53D23003260006"]}]},{"name":"Italian Ministry of Ministry of University and Research (MUR)","award":["104"],"award-info":[{"award-number":["104"]}]},{"name":"Italian Ministry of Ministry of University and Research (MUR)","award":["1015"],"award-info":[{"award-number":["1015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Disorders of sexual development (DSDs) in dogs, similar to humans, arise from genetic mutations, gonadal differentiation, or phenotypic sex development. The French Bulldog, a breed that has seen a surge in popularity and demand, has also shown a marked increase in DSD incidence. This study aims to characterize the genetic underpinnings of DSDs in a French Bulldog named Brutus, exhibiting ambiguous genitalia and internal sexual anatomy, and to explore the impact of breeding practices on genetic diversity within the breed. We utilized a comprehensive approach combining conventional cytogenetics, molecular techniques, and deep sequencing to investigate the genetic profile of Brutus. The sequence data were compared to three other male French Bulldogs\u2019 genome sequences with typical reproductive anatomy, including Brutus\u2019s father and the canine reference genome (CanFam6). We found a Robertsonian fusion involving chromosome 23 previously reported in dogs as a causative mutation responsible for sex reversal syndrome. Our findings revealed a 22% mosaicism (78,XX\/77,XX), the absence of the sex-determining region (SRY) gene, and the presence of 43 unique Single Nucleotide Variants (SNVs) not inherited from the father. Notably, the run of homozygosity (ROH) analysis showed Brutus has a higher number of homozygous segments compared to other Bulldogs, with a total length of these fragments 50% greater than the average, strongly suggesting this dog is the product of the mating between siblings. Although no direct causative genes for the DSD phenotype were identified, four candidate loci warrant further investigation. Our study highlighted the need for a better annotated and curated reference dog genome to define genes causative of any specific phenotype, suggests a potential genetic basis for the DSD phenotype in dogs, and underscores the consequences of uncontrolled breeding practices in French Bulldogs. These findings highlight the importance of implementing strategic genetic management to preserve genetic health and diversity in canine populations.<\/jats:p>","DOI":"10.3390\/ijms251910763","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:23:18Z","timestamp":1728282198000},"page":"10763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genomic Sequencing to Detect Cross-Breeding Quality in Dogs: An Example Studying Disorders in Sexual Development"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9572-7630","authenticated-orcid":false,"given":"Luciana","family":"de Gennaro","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari, Via Orabona 4, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-4540","authenticated-orcid":false,"given":"Matteo","family":"Burgio","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Bari Aldo Moro, S.P. per Casamassima km. 3, 70010 Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9109-3561","authenticated-orcid":false,"given":"Giovanni Michele","family":"Lacalandra","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Bari Aldo Moro, S.P. per Casamassima km. 3, 70010 Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Petronella","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Bari Aldo Moro, S.P. per Casamassima km. 3, 70010 Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5995-2001","authenticated-orcid":false,"given":"Alberto","family":"L\u2019Abbate","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes, Bioenergetics, and Molecular Biotechnology (IBIOM), 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2866-5533","authenticated-orcid":false,"given":"Francesco","family":"Ravasini","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u2018Charles Darwin\u2019, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beniamino","family":"Trombetta","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u2018Charles Darwin\u2019, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2688-0056","authenticated-orcid":false,"given":"Annalisa","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Bari Aldo Moro, S.P. per Casamassima km. 3, 70010 Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7762-8777","authenticated-orcid":false,"given":"Mario","family":"Ventura","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari, Via Orabona 4, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2792-8848","authenticated-orcid":false,"given":"Vincenzo","family":"Cicirelli","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Bari Aldo Moro, S.P. per Casamassima km. 3, 70010 Valenzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/j.theriogenology.2012.07.010","article-title":"Disorders of sexual development and associated changes in the pituitary-gonadal axis in dogs","volume":"78","author":"Buijtels","year":"2012","journal-title":"Theriogenology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000506582","article-title":"Disorders of Sex Development Are an Emerging Problem in French Bulldogs: A Description of Six New Cases and a Review of the Literature","volume":"13","author":"Szczerbal","year":"2020","journal-title":"Sex. 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