Animal genetics最新文献

{"title":"Identification of a novel QTL for lean meat percentage using imputed genotypes","authors":"Emil Ibragimov,&nbsp;Anni Øyan Pedersen,&nbsp;Niels Morten Sloth,&nbsp;Merete Fredholm,&nbsp;Peter Karlskov-Mortensen","doi":"10.1111/age.13442","DOIUrl":"10.1111/age.13442","url":null,"abstract":"<p>Lean meat percentage is a critical production trait in pig breeding systems with direct implications for the sustainability of the industry. In this study, we conducted a genome-wide association study for lean meat percentage using a cohort of 850 Duroc × (Landrace × Yorkshire) crossbred pigs and we identified QTL on SSC3 and SSC18. Based on the predicted effect of imputed variants and using the PigGTEx database of molecular QTL, we prioritized candidate genes and SNPs located within the QTL regions, which may be involved in the regulation of porcine leanness. Our results indicate that a nonsense mutation in <i>ZC3HAV1L</i> on SSC18 has a direct effect on lean meat percentage.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"658-663"},"PeriodicalIF":1.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of RPGRIP1 and MAP9 genetic modifiers of canine progressive retinal atrophy, in 132 breeds of dog","authors":"Jonas Donner,&nbsp;Cathryn Mellersh","doi":"10.1111/age.13443","DOIUrl":"10.1111/age.13443","url":null,"abstract":"<p>Variants in <i>RPGRIP1</i> and <i>MAP9</i>, termed <i>RPGRIP1</i>ins44 and <i>MAP9</i>del respectively, are both associated with a form of canine progressive retinal atrophy referred to as <i>RPGRIP1</i>-CRD and have both been demonstrated to modify the development and progression of this disease. In the current study both variants were genotyped in at least 50 dogs of 132 diverse breeds and the data reveal that both segregate in multiple breeds. Individually, each variant is common within largely non-overlapping subsets of breed, and there is a negative correlation between their frequencies within breeds that segregate both variants. The frequency of both variants exceeds 0.05 in a single breed only, the Miniature Longhaired Dachshund. These data indicate that both variants are likely to be ancient and predate the development and genetic isolation of modern dog breeds. That both variants are present individually at high frequency in multiple breeds is consistent with the hypothesis that homozygosity of either variant alone is not associated with a clinically relevant phenotype, whereas the negative correlation between the two variants is consistent with the application of selective pressure, from dog breeders, against homozygosity at both loci, probably due to the more severe phenotype associated with homozygosity at both loci.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"687-691"},"PeriodicalIF":1.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residual network improves the prediction accuracy of genomic selection","authors":"Huaxuan Wu,&nbsp;Bingxi Gao,&nbsp;Rong Zhang,&nbsp;Zehang Huang,&nbsp;Zongjun Yin,&nbsp;Xiaoxiang Hu,&nbsp;Cai-Xia Yang,&nbsp;Zhi-Qiang Du","doi":"10.1111/age.13445","DOIUrl":"10.1111/age.13445","url":null,"abstract":"<p>Genetic improvement of complex traits in animal and plant breeding depends on the efficient and accurate estimation of breeding values. Deep learning methods have been shown to be not superior over traditional genomic selection (GS) methods, partially due to the degradation problem (i.e. with the increase of the model depth, the performance of the deeper model deteriorates). Since the deep learning method residual network (ResNet) is designed to solve gradient degradation, we examined its performance and factors related to its prediction accuracy in GS. Here we compared the prediction accuracy of conventional genomic best linear unbiased prediction, Bayesian methods (BayesA, BayesB, BayesC, and Bayesian Lasso), and two deep learning methods, convolutional neural network and ResNet, on three datasets (wheat, simulated and real pig data). ResNet outperformed other methods in both Pearson's correlation coefficient (PCC) and mean squared error (MSE) on the wheat and simulated data. For the pig backfat depth trait, ResNet still had the lowest MSE, whereas Bayesian Lasso had the highest PCC. We further clustered the pig data into four groups and, on one separated group, ResNet had the highest prediction accuracy (both PCC and MSE). Transfer learning was adopted and capable of enhancing the performance of both convolutional neural network and ResNet. Taken together, our findings indicate that ResNet could improve GS prediction accuracy, affected potentially by factors such as the genetic architecture of complex traits, data volume, and heterogeneity.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"599-611"},"PeriodicalIF":1.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterozygous COL5A1 deletion in a cat with classical Ehlers–Danlos syndrome","authors":"Stefan J. Rietmann,&nbsp;Sarah Nowell,&nbsp;M. Kelly Keating,&nbsp;Cynthia Bauer,&nbsp;Vidhya Jagannathan,&nbsp;Tosso Leeb","doi":"10.1111/age.13446","DOIUrl":"10.1111/age.13446","url":null,"abstract":"&lt;p&gt;Classical Ehlers–Danlos syndrome (cEDS) represents one of 14 subtypes of EDS, hereditary connective tissue disorders characterized by skin hyperextensibility, poor wound healing and, especially in human patients, joint hypermobility (Bowen et al., &lt;span&gt;2017&lt;/span&gt;; Malfait et al., &lt;span&gt;2020&lt;/span&gt;). cEDS is frequently inherited as an autosomal dominant trait and caused by pathogenic variants in the &lt;i&gt;COL5A1&lt;/i&gt; gene encoding the α-1 subunit of collagen type V (Mak et al., &lt;span&gt;2016&lt;/span&gt;; Symoens et al., &lt;span&gt;2012&lt;/span&gt;). Collagen type V represents only a small percentage of the total collagen content in most tissues but plays a key role in regulating collagen fibrillogenesis (Malfait et al., &lt;span&gt;2020&lt;/span&gt;). In cats, five different causative variants for cEDS have been reported in the &lt;i&gt;COL5A1&lt;/i&gt; gene so far (Kiener et al., &lt;span&gt;2022&lt;/span&gt;; McElroy et al., &lt;span&gt;2023&lt;/span&gt;; Spycher et al., &lt;span&gt;2018&lt;/span&gt;; OMIA:002165-9685). In this study, we investigated a female Maine Coon cat with suspected EDS due to complications in wound healing.&lt;/p&gt;&lt;p&gt;The 10-month-old female Maine Coon was presented to a specialty dermatology practice for referral and consultation regarding a nonhealing spay incision. The wound had shown minimal bleeding but had not resolved after multiple attempts at corrective surgery. On initial physical examination, the cat showed bilateral alopecia of the concave and multiple small wounds at the base of the pinnae from self-trauma. Scarring was present on the base of neck and the preauricular region. The wound associated with the spay incision was healed at the time of presentation, but a white scar persisted. Skin elasticity index was determined to be 23% (Figure 1a). The remaining physical examination was unremarkable.&lt;/p&gt;&lt;p&gt;Histopathological examination of a skin biopsy from the cat revealed mildly decreased dermal thickness. Collagen fibers were of variable size and width and increased numbers of fibroblasts were present in some regions (Figure 1b). The epidermis was of normal thickness and the hair follicles and adnexa present in adequate number.&lt;/p&gt;&lt;p&gt;Genomic DNA of the cat was isolated from an EDTA-blood sample. A PCR-free library was prepared and sequenced with 2 × 150-bp reads at 22× coverage. The sequencing reads were aligned to the F.catus_Fcat126_mat1.0 reference assembly and variant calling was performed as described (Jagannathan et al., &lt;span&gt;2019&lt;/span&gt;). Comparison to 87 control genomes (Table S1) yielded three homozygous and 182 heterozygous private protein changing variants (Table S2). However, none of these variants were located in any of the 20 known functional candidate genes for EDS that were analyzed (Table S3).&lt;/p&gt;&lt;p&gt;Therefore, the short-read alignments of the affected cat were visually inspected for structural variants in the same 20 candidate genes using the Integrative Genomics Viewer (Robinson et al., &lt;span&gt;2011&lt;/span&gt;). This led to the discovery of a heterozygous deletion spanning 33 7","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"705-707"},"PeriodicalIF":1.8,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRT5 in-frame deletion in a family of German Shepherd dogs with split paw pad disease resembling localized epidermolysis bullosa simplex in human patients","authors":"Stefan J. Rietmann,&nbsp;Anja Lange,&nbsp;Sara Soto,&nbsp;Nina Thom,&nbsp;Eberhard Manz,&nbsp;Vidhya Jagannathan,&nbsp;Ursula Mayer,&nbsp;Tosso Leeb","doi":"10.1111/age.13444","DOIUrl":"10.1111/age.13444","url":null,"abstract":"<p>Split paw pad disease is a scarcely defined phenotype characterized by skin lesions on the paw pads of dogs. We studied a family of German Shepherd dogs, in which four dogs developed intermittent paw pad lesions and lameness. The paw pads of two of the affected dogs were biopsied and demonstrated cleft formation in the stratum spinosum and stratum corneum, the outermost layers of the epidermis. Whole genome sequencing data from an affected dog revealed a private heterozygous 18 bp in frame deletion in the <i>KRT5</i> gene. The deletion NM_001346035.1:c.988_1005del or NP_001332964.1:p.(Asn330_Asp335del) is predicted to lead to a loss of six amino acids in the L12 linker domain of the encoded keratin 5. <i>KRT5</i> variants in human patients lead to various subtypes of epidermolysis bullosa simplex (EBS). Localized EBS is the mildest of the <i>KRT5</i>-related human diseases and may be caused by variants affecting the L12 linker domain of keratin 5. We therefore think that the detected <i>KRT5</i> deletion in dogs represents a candidate causal variant for the observed skin lesions in dogs. However, while the clinical phenotype of <i>KRT5</i>-mutant dogs of this study closely resembles human patients with localized EBS, there are differences in the histopathology. EBS is defined by cleft formation within the basal layer of the epidermis while the cleft formation in the dogs described herein occurred in the outermost layers, a hallmark of split paw pad disease. Our study provides a basis for further studies into the exact relation of split paw pad disease and EBS.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"692-696"},"PeriodicalIF":1.8,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-genome resequencing deciphers patterns of genetic diversity, phylogeny, and evolutionary dynamics in Kashmir cattle","authors":"Zulfiqar Ahmed,&nbsp;Weixuan Xiang,&nbsp;Fuwen Wang,&nbsp;Mohsin Nawaz,&nbsp;Zulfiqar Hussan Kuthu,&nbsp;Chuzhao Lei,&nbsp;Dequan Xu","doi":"10.1111/age.13434","DOIUrl":"10.1111/age.13434","url":null,"abstract":"<p>Kashmir cattle, which were kept by local pastoralists for centuries, are exceptionally resilient and adaptive to harsh environments. Despite its significance, the genomic characteristics of this cattle breed remain elusive. This study utilized whole genome sequences of Kashmir cattle (<i>n</i> = 20; newly sequenced) alongside published whole genomes of 32 distinct breeds and seven core cattle populations (<i>n</i> = 135). The analysis identified ~25.87 million biallelic single nucleotide polymorphisms in Kashmir cattle, predominantly in intergenic and intron regions. Population structure analyses revealed distinct clustering patterns of Kashmir cattle with proximity to the South Asian, African and Chinese indicine cattle populations. Genetic diversity analysis of Kashmir cattle demonstrated lower inbreeding and greater nucleotide diversity than analyzed global breeds. Homozygosity runs indicated less consanguineous mating in Kashmir cattle compared with European taurine breeds. Furthermore, six selection sweep detection methods were used within Kashmir cattle and other cattle populations to identify genes associated with vital traits, including immunity (<i>BOLA-DQA5</i>, <i>BOLA-DQB</i>, <i>TNFAIP8L</i>, <i>FCRL4</i>, <i>AOAH</i>, <i>HIF1AN</i>, <i>FBXL3</i>, <i>MPEG1</i>, <i>CDC40</i>, etc.), reproduction (<i>GOLGA4</i>, <i>BRWD1</i>, <i>OSBP2</i>, <i>LEO1 ADCY5</i>, etc.), growth (<i>ADPRHL1</i>, <i>NRG2</i>, <i>TCF12</i>, <i>TMOD4</i>, <i>GBP4</i>, <i>IGF2</i>, <i>RSPO3</i>, <i>SCD</i>, etc.), milk composition (<i>MRPS30</i> and <i>CSF1</i>) and high-altitude adaptation (<i>EDNRA</i>, <i>ITPR2</i>, <i>AGBL4</i> and <i>SCG3</i>). These findings provide essential genetic insights into the characteristics and establish the foundation for the scientific conservation and utilization of Kashmir cattle breed.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"511-526"},"PeriodicalIF":1.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective sweep analysis of the adaptability of the Yarkand hare (Lepus yarkandensis) to hot arid environments using SLAF-seq","authors":"Zurui Li,&nbsp;Bingwa Fang,&nbsp;Pengcheng Dong,&nbsp;Wenjuan Shan","doi":"10.1111/age.13440","DOIUrl":"10.1111/age.13440","url":null,"abstract":"<p>The Yarkand hare (<i>Lepus yarkandensis</i>) inhabits arid desert areas and is endemic to China. It has evolved various adaptations to survive in hot arid environments, including stress responses, the ability to maintain water homeostasis and heat tolerance. Here, we performed a selective sweep analysis to identify the candidate genes for adaptation to hot arid environments in the Yarkand hare. A total of 397 237 single-nucleotide polymorphisms were obtained from 80 Yarkand hares, which inhabit hot arid environments, and 36 Tolai hares (<i>Lepus tolai</i>), which inhabit environments with a mild climate, via specific-locus amplified fragment sequencing. We identified several candidate genes that were associated with the heat stress response (<i>HSPE1</i>), oxidative stress response (<i>SLC23A</i> and <i>GLRX2</i>), immune response (<i>IL1R1</i> and <i>IRG1</i>), central nervous system development (<i>FGF13</i>, <i>THOC2</i>, <i>FMR1</i> and <i>MECP2</i>) and regulation of water homeostasis (<i>CDK1</i>) according to fixation index values and <i>θ</i>_<i>π</i> ratios in the selective sweep analysis, and six of these genes (<i>GLRX2</i>, <i>IRG1</i>, <i>FGF13</i>, <i>FMR1</i>, <i>MECP2</i> and <i>CDK1</i>) are newly discovered genes. To the best of our knowledge, this is the first study to identify candidate genes for adaptation to hot arid environments in the Yarkand hare. The results of this study enhance our understanding of the adaptation of the Yarkand hare to hot arid environments and will aid future studies aiming to functionally verify these candidate genes.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"681-686"},"PeriodicalIF":1.8,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new Finnish flavor of feline coat coloration, “salmiak,” is associated with a 95-kb deletion downstream of the KIT gene","authors":"Heidi Anderson,&nbsp;Milla Salonen,&nbsp;Sari Toivola,&nbsp;Matthew Blades,&nbsp;Leslie A. Lyons,&nbsp;Oliver P. Forman,&nbsp;Marjo K. Hytönen,&nbsp;Hannes Lohi","doi":"10.1111/age.13438","DOIUrl":"10.1111/age.13438","url":null,"abstract":"<p>Cats with a distinctive white hair pattern of unknown molecular cause have been discovered in the Finnish domestic cat population. Based on the unique appearance of these cats, we have named this phenotype salmiak (“salty licorice”). The use of a commercially available panel test to genotype four salmiak-colored cats revealed the absence of all known variants associated with white-haired phenotypic loci: full White (<i>W</i>), Spotting (<i>W</i>^<i>s</i>) and the Birman white Gloves associated (<i>w</i>^<i>g</i>) allele of the <i>KIT proto-oncogene</i> (<i>KIT</i>) gene. Whole-genome sequencing on two salmiak-colored cats was conducted to search for candidate causal variants in the <i>KIT</i> gene. Despite a lack of coding variants, visual inspection of the short read alignments revealed a large ~95 kb deletion located ~65 kb downstream of the <i>KIT</i> gene in the salmiak cats. Additional PCR genotyping of 180 domestic cats and three salmiak-colored cats confirmed the homozygous derived variant genotype fully concordant with the salmiak phenotype. We suggest the newly identified variant be designated as <i>w</i>^<i>sal</i> for “w salmiak”.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"676-680"},"PeriodicalIF":1.8,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic analysis of inbreeding level, kinship and breed relationships in Creole cattle from South America","authors":"O. Marcuzzi,&nbsp;F. Calcaterra,&nbsp;A. Loza Vega,&nbsp;M. F. Ortega Masagué,&nbsp;E. Armstrong,&nbsp;J. A. Pereira Rico,&nbsp;E. Jara,&nbsp;L. H. Olivera,&nbsp;P. Peral García,&nbsp;G. Giovambattista","doi":"10.1111/age.13435","DOIUrl":"10.1111/age.13435","url":null,"abstract":"<p>The conservation of animal genetic resources refers to measures taken to prevent the loss of genetic diversity in livestock populations, including the protection of breeds from extinction. Creole cattle populations have suffered a drastic reduction in recent decades owing to absorbent crosses or replacement with commercial breeds of European or Indian origin. Genetic characterization can serve as a source of information for conservation strategies to maintain genetic variation. The objective of this work was to evaluate the levels of inbreeding and kinship through the use of genomic information. A total of 903 DNAs from 13 cattle populations from Argentina, Bolivia and Uruguay were genotyped using an SNP panel of 48 K. Also, a dataset of 76 K SNPs from Peruvian Creole was included. Two inbreeding indices (<i>F</i>_ROH and <i>Fhat2</i>) and kinship relationships were calculated. In addition, effective population size (<i>N</i>_e), linkage disequilibrium, population composition and phylogenetic relationships were estimated. In Creole cattle, <i>F</i>_ROH ranged from 0.14 to 0.03, and <i>Fhat2</i> was close to zero. The inferred <i>N</i>_<i>e</i> trends exhibited a decline toward the present for all populations, whereas Creole cattle presented a lower magnitude of <i>N</i>_e than foreign breeds. Cluster analysis clearly differentiated the taurine and Zebu components (K2) and showed that Bolivian Creole cattle presented Zebu gene introgression. Despite the population reduction, Creole populations did not present extreme values of consanguinity and kinship and maintain high levels of genetic diversity. The information obtained in this work may be useful for planning conservation programmes for these valuable local animal genetic resources.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"527-539"},"PeriodicalIF":1.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intragenic MFSD8 duplication and histopathological findings in a rabbit with neuronal ceroid lipofuscinosis","authors":"Matthias Christen,&nbsp;Katharina M. Gregor,&nbsp;Ariane Böttcher-Künneke,&nbsp;Mara S. Lombardo,&nbsp;Wolfgang Baumgärtner,&nbsp;Vidhya Jagannathan,&nbsp;Christina Puff,&nbsp;Tosso Leeb","doi":"10.1111/age.13441","DOIUrl":"10.1111/age.13441","url":null,"abstract":"<p>Neuronal ceroid lipofuscinoses (NCL) are among the most prevalent neurodegenerative disorders of early life in humans. Disease-causing variants have been described for 13 different NCL genes. In this study, a refined pathological characterization of a female rabbit with progressive neurological signs reminiscent of NCL was performed. Cytoplasmic pigment present in neurons was weakly positive with Sudan black B and autofluorescent. Immunohistology revealed astrogliosis, microgliosis and axonal degeneration. During the subsequent genetic investigation, the genome of the affected rabbit was sequenced and examined for private variants in NCL candidate genes. The analysis revealed a homozygous ~10.7 kb genomic duplication on chromosome 15 comprising parts of the <i>MFSD8</i> gene, NC_013683.1:g.103,727,963_103,738,667dup. The duplication harbors two internal protein coding exons and is predicted to introduce a premature stop codon into the transcript, truncating ~50% of the wild-type <i>MFSD8</i> open reading frame encoding the major facilitator superfamily domain containing protein 8, XP_002717309.2:p.(Glu235Leufs*23). Biallelic loss-of-function variants in <i>MFSD8</i> have been described to cause NCL7 in human patients, dogs and a single cat. The available clinical and pathological data, together with current knowledge about <i>MFSD8</i> variants and their functional impact in other species, point to the <i>MFSD8</i> duplication as a likely causative defect for the observed phenotype in the affected rabbit.</p>","PeriodicalId":7905,"journal":{"name":"Animal genetics","volume":"55 4","pages":"588-598"},"PeriodicalIF":1.8,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/age.13441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}