Person:
Sevane Fernández, Natalia

First Name

Natalia

Last Name

Sevane Fernández

URI

https://hdl.handle.net/20.500.14352/80476

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Veterinaria

Department

Producción Animal

Area

Producción Animal

Identifiers

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Now showing 1 - 10 of 28

Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity
(International Journal of Molecular Sciences, 2023) Barreno San Antolín, Lucía; Sevane Fernández, Natalia; Valdivia Lara, Edgar Guillermo; Alonso Miguel, Daniel; Suárez Redondo, María; Alonso Díez, Ángela; Fiering, Steven; Beiss, Veronique; Steinmetz, Nicole F.; Pérez Alenza, María De Los Dolores; Peña Fernández, Laura Luisa
Canine inflammatory mammary cancer (IMC) is a highly aggressive and lethal cancer in dogs serving as a valuable animal model for its human counterpart, inflammatory breast cancer (IBC), both lacking effective therapies. Intratumoral immunotherapy (IT-IT) with empty cowpea mosaic virus (eCPMV) nanoparticles has shown promising results, demonstrating a reduction in tumor size, longer survival rates, and improved quality of life. This study compares the transcriptomic profiles of tumor samples from female dogs with IMC receiving eCPMV IT-IT and medical therapy (MT) versus MT alone. Transcriptomic analyses, gene expression profiles, signaling pathways, and cell type profiling of immune cell populations in samples from four eCPMV-treated dogs with IMC and four dogs with IMC treated with MT were evaluated using NanoString Technologies using a canine immune-oncology panel. Comparative analyses revealed 34 differentially expressed genes between treated and untreated samples. Five genes (CXCL8, S100A9, CCL20, IL6, and PTGS2) involved in neutrophil recruitment and activation were upregulated in the treated samples, linked to the IL17-signaling pathway. Cell type profiling showed a significant increase in neutrophil populations in the tumor microenvironment after eCPMV treatment. These findings highlight the role of neutrophils in the anti-tumor response mediated by eCPMV IT-IT and suggest eCPMV as a novel therapeutic approach for IBC/IMC.
Conservation priorities of Iberoamerican pig breeds and their ancestors based on microsatellite information
(Heredity, 2016) Cortés Gardyn, Óscar; Martínez, A. M.; Cañón Ferreras, Francisco Javier; Sevane Fernández, Natalia; Gama, L. T.; Ginja, C.; Landi, V.; Zaragoza, P.; Carolino, N.; Vicente, A.; Sponenberg, P.; Delgado, J. V.; BioPig Consortium
Criollo pig breeds are descendants from pigs brought to the American continent starting with Columbus second trip in 1493. Pigs currently play a key role in social economy and community cultural identity in Latin America. The aim of this study was to establish conservation priorities among a comprehensive group of Criollo pig breeds based on a set of 24 microsatellite markers and using different criteria. Spain and Portugal pig breeds, wild boar populations of different European geographic origins and commercial pig breeds were included in the analysis as potential genetic influences in the development of Criollo pig breeds. Different methods, differing in the weight given to within- and between-breed genetic variability, were used in order to estimate the contribution of each breed to global genetic diversity. As expected, the partial contribution to total heterozygosity gave high priority to Criollo pig breeds, whereas Weitzman procedures prioritized Iberian Peninsula breeds. With the combined within- and between-breed approaches, different conservation priorities were achieved. The Core Set methodologies highly prioritized Criollo pig breeds (Cr. Boliviano, Cr. Pacifico, Cr. Cubano and Cr. Guadalupe). However, weighing the between- and within-breed components with FST and 1-FST, respectively, resulted in higher contributions of Iberian breeds. In spite of the different conservation priorities according to the methodology used, other factors in addition to genetic information also need to be considered in conservation programmes, such as the economic, cultural or historical value of the breeds involved.
New single nucleotide polymorphisms in Alectoris identified using chicken genome information allow Alectoris introgression detection
(Molecular Ecology Resources, 2010) Sevane Fernández, Natalia; Cortés Gardyn, Óscar; García D; Cañón Ferreras, Francisco Javier; Dunner Boxberger, Helene Susana
Using the chicken genome, 114 polymorphisms (109 SNPs and 5 INDELs) were identified in the Alectoris genus by polymerase chain reaction–single strand conformation polymorphism. Using these, a panel of SNPs is described, which allows easy detection of introgression of Alectoris chukar in wild Alectoris rufa populations, when used with a primer extension protocol. The selected polymorphisms were genotyped and their allelic frequencies estimated on 98 A. rufa partridges sampled from nonrestocking Spanish areas, and 63 A. chukar partridges from Greek and Spanish farms. Power calculations to determine an optimum subset of markers for a given significance level were performed.
Syringohydromyelia in Dogs: The Genomic Component Underlying a Complex Neurological Disease
(Animals, 2022) Andrino García, Sandra; Lorenzo, Valentina; Dunner Boxberger, Helene Susana; Contreras Alcaide, Elisabeth; Cañón Ferreras, Francisco Javier; Sevane Fernández, Natalia
Syringohydromyelia (SHM) is a neurological disorder characterized by the appearance of fluid-containing cavities within the spinal cord. Although SHM is thought to be under multigenic control, the molecular basis of this disease remains poorly defined. A genome-wide association study (GWAS) was carried out comparing the whole genome sequences (WGS) from 12 dogs with SHM and 2 panels of 26 dogs (either older than 5 years and showing the absence of SHM or belonging to breeds not susceptible to SHM) to identify candidate genes associated with the development of SHM. Seven candidate genes were identified. Of these, five genes were determined to be involved in bone development (PLXNA2, HHAT, MBOAT2, ITGAV) and calcium homeostasis (HPCAL1). Although further validation is needed at the transcript level, it is worth highlighting the association of a possible pathogenic variant which generated a new intronic branch-site sequence in PLXNA2 (T/C, CFA7:7043294). Considering previous studies in dogs that show SHM related to craniocervical junction (CCJ) malformations, these genes can be considered good candidates for the development of this disease. This report dissects the genomic component of SHM in dogs, which paves the way for further research on this complex disease found both in canine and human species.
Genes involved in muscle lipid composition in 15 European Bos taurus breeds
(Animal Genetics, 2013) Dunner Boxberger, Helene Susana; Sevane Fernández, Natalia; Garcia D; Levéziel H; Williams JL; Mangin B; Valentini A
Consumers demand healthy and palatable meat, both factors being affected by fat composition. However, red meat has relatively high concentration of saturated fatty acids and low concentration of the beneficial polyunsaturated fatty acids. To select animals prone to produce particular fat types, it is necessary to identify the genes influencing muscle lipid composition. This paper describes an association study in which a large panel of candidate genes involved in adipogenesis, lipid metabolism and energy homoeostasis was tested for effects on fat composition in 15 European cattle breeds. Sixteen genes were found to have significant effects on different lipid traits, and among these, CFL1 and MYOZ1 were found to have large effects on the ratio of 18:2/18:3, CRI1 on the amount of neutral adrenic acid (22:4 n-6), MMP1 on docosahexaenoic acid (22:6 n-3) and conjugated linoleic acid, PLTP on the ratio of n-6:n-3 and IGF2R on flavour. Several genes – ALDH2, CHRNE, CRHR2, DGAT1, IGFBP3, NEB, SOCS2, SUSP1, TCF12 and FOXO1 – also were found to be associated with both lipid and organoleptic traits although with smaller effect. The results presented here help in understanding the genetic and biochemical background underlying variations in fatty acid composition and flavour in beef.
Phenotypic and genotypic background underlying variations in fatty acid composition and sensory parameters in European bovine breeds
(Journal of Animal Science and Biotechnology, 2014) Sevane Fernández, Natalia; Levéziel, Hubert; Nute, Geoffrey R.; Sañudo, Carlos; Valentini, Alessio; Williams, John L.; Dunner Boxberger, Helene Susana; GemQual Consortium
Background: Consuming moderate amounts of lean red meat as part of a balanced diet valuably contributes to intakes of essential nutrients. In this study, we merged phenotypic and genotypic information to characterize the variation in lipid profile and sensory parameters and to represent the diversity among 15 cattle populations. Correlations between fat content, organoleptic characteristics and lipid profiles were also investigated. Methods: A sample of 436 largely unrelated purebred bulls belonging to 15 breeds and reared under comparable management conditions was analyzed. Phenotypic data -including fatness score, fat percentage, individual fatty acids (FA) profiles and sensory panel tests- and genotypic information from 11 polymorphisms was used. Results: The correlation coefficients between muscle total lipid measurements and absolute vs. relative amounts of polyunsaturated FA (PUFA) were in opposite directions. Increasing carcass fat leads to an increasing amount of FAs in triglycerides, but at the same time the relative amount of PUFAs is decreasing, which is in concordance with the negative correlation obtained here between the percentage of PUFA and fat measurements, as well as the weaker correlation between total phospholipids and total lipid muscle content compared with neutral lipids. Concerning organoleptic characteristics, a negative correlation between flavour scores and the percentage of total PUFA, particularly to n-6 fraction, was found. The correlation between juiciness and texture is higher than with flavour scores. The distribution of SNPs plotted by principal components analysis (PCA) mainly reflects their known trait associations, although influenced by their specific breed allele frequencies. Conclusions: The results presented here help to understand the phenotypic and genotypic background underlying variations in FA composition and sensory parameters between breeds. The wide range of traits and breeds studied, along with the genotypic information on polymorphisms previously associated with different lipid traits, provide a broad characterization of beef meat, which allows giving a better response to the variety of consumers’ preferences. Also, the development and implementation of low-density SNP panels with predictive value for economically important traits, such as those summarized here, may be used to improve production efficiency and meat quality in the beef industry.
A novel missense variant in endothelin‐2 ( EDN2 ) causes a growth and respiratory lethal syndrome in bovine
(Animal Genetics, 2022) Eusebi, Paulina G.; Cortés Gardyn, Óscar; Contreras, Elisabeth; Cañón Ferreras, Francisco Javier; Dunner Boxberger, Helene Susana; Sevane Fernández, Natalia
The high level of fragmentation of the Spanish Lidia cattle breed, divided into lineages called ‘castas’ and into herds within lineages based on reproductive isolation, increases the risk of homozygosity and the outbreak of recessive genetic defects. Since 2004, an increasing number of calves have been identified in a Lidia herd with signs of severe growth retardation, respiratory alterations and juvenile lethality, which constitutes a novel inherited syndrome in cattle and was subsequently termed growth and respiratory lethal syndrome. We performed a genome-wide association study on a cohort of 13 affected calves and 24 putative non-carrier parents, mapping the disease to a wide 6 cM region on bovine chromosome 3 (p < 10−7). Whole genome re-sequencing of three affected calves and three putative non-carrier parents identified a novel missense variant (c.149G>A|p.Cys50Tyr) in exon 2 of the endothelin 2 (EDN2) gene. Bioinformatic analyses of p.Cys50Tyr effects predicted them to be damaging for both the structure and the function of the edn2 protein, and to create a new site of splicing that may also affect the pattern of pre-mRNA splicing and exon definition. Sanger sequencing of this variant on the rest of the sample set confirmed the segregation pattern obtained with whole genome re-sequencing. The identification of the causative variant and the development of a diagnostic genetic test enable the efficient design of matings to keep the effective population size as high as possible, as well as providing insights into the first EDN2-associated hereditary disease in cattle or other species.
Explicit evidence for a missense mutation in exon 4 of SLC45A2 gene causing the pearl coat dilution in horses
(Animal Genetics, 2019) Sevane Fernández, Natalia; Sanz, C. R.; Dunner Boxberger, Helene Susana
Four loci seem responsible for the dilution of the basic coat colours in horse: Dun (D), Silver Dapple (Z), Champagne (CH) and Cream (C). Apart from the current phenotypes ascribed to these loci, pearl has been described as yet another diluted coat colour in this species. To date, this coat colour seems to segregate only in the Iberian breeds Purebred Spanish horse and Lusitano and has also been described in breeds of Iberian origin, such as Quarter Horses and Paint Horse, where it is referred to as the ‘Barlink Factor’. This phenotype segregates in an autosomal recessive manner and resembles some of the coat colours produced by the champagne CHCH and cream CCr alleles, sometimes being difficult to distinguish among them. The interaction between compound heterozygous for the pearl Cprl and cream CCr alleles makes SLC45A2 the most plausible candidate gene for the pearl phenotype in horses. Our results provide documented evidence for the missense variation in exon 4 [SLC45A2:c.985G>A; SLC45A2:p.(Ala329Thr)] as the causative mutation for the pearl coat colour. In addition, it is most likely involved as well in the cremello, perlino and smoky cream like phenotypes associated with the compound CCr and Cprl heterozygous genotypes (known as cream pearl in the Purebred Spanish horse breed). The characterization of the pearl mutation allows breeders to identify carriers of the Cprl allele and to select this specific coat colour according to personal preferences, market demands or studbook requirements as well as to verify segregation within particular pedigrees.
SNPs included in candidate genes involved in muscle, lipid and energy metabolism behave like neutral markers
(Animal Production Science, 2015) Sevane Fernández, Natalia; Cañón Ferreras, Francisco Javier; Williams, John L.; Levéziel, Hubert; Valentini, Alessio; Dunner Boxberger, Helene Susana; GemQual Consortium
Studies of population structure and diversity in cattle have provided insights into the origins of breeds, their history and evolution, and allow the identification of global livestock diversity hotspots, which is important for conservation of diversity. Genetic diversity, genetic relationship, population structure, and the presence of hotspots of genetic diversity among 15 European bovine breeds from five countries were assessed using 435 single nucleotide polymorphisms (SNP) markers identified in candidate genes for muscle, lipid and energy metabolism, thus providing the opportunity to compare the breed relationships obtained using putatively functional markers with previous data using neutral loci. Individuals belonging to 11 breeds tended to be clearly assigned to a single cluster when the number of pre-defined populations reached a maximum in the likelihood of the data at K = 12, whereas Asturiana de los Valles, Danish Red, Simmental, and Avileña-Negra Ibérica displayed a greater degree of admixture, which may be explained by their diverse ancestry. Although overall results were in agreement with those reported by studies based on neutral genetic variations, some additional breed relationship information emerged using markers in candidate functional loci, including the relationship between the Asturiana de los Valles and Piedmontese, and Danish Red and Charolais breeds. This study indicates that the analysed loci have not been main targets for selection or for adaptation processes, but also that SNP within candidate genes related with beef characteristics and performance may provide a slightly new perspective on past breeding and may also help in the development of strategies for the rational conservation of livestock diversity.
Polymorphisms in ten candidate genes are associated with conformational and locomotive traits in Spanish Purebreed horses
(Journal of Applied Genetics, 2016) Sevane Fernández, Natalia; Dunner Boxberger, Helene Susana; Boado, Ana; Cañón Ferreras, Francisco Javier
The Spanish Purebred horses, also known as Andalusian horses, compete to the highest standards in international dressage events. Gait and conformation could be used as early selection criteria to detect young horses with promising dressage ability. Although the genetic background of equine size variation has been recently uncovered, the genetic basis of horse conformational and locomotive traits is not known, hampered by the complex genetic architecture underlying quantitative traits and the lack of phenotypic data. The aim of this study was to validate the loci associated with size in 144 Spanish Purebred horses, and to seek novel associations between loci previously associated with the development of osteochondrosis (OC) lesions and 20 conformational and locomotive traits. Ten loci were associated with different conformational and locomotive traits (LCORL/NCAPG, HMGA2, USP31, MECR, COL24A1, MGP, FAM184B, PTH1R, KLF3 and SGK1), and the LCORL/NCAPG association with size in the Spanish Purebred horse was validated. Except for HMGA2, all polymorphisms seem to influence both the prevalence of OC lesions and morphological characters, supporting the link between conformation and OC. Also, the implication of most genes in either immune and inflammatory responses and cellular growth, or ossification processes, reinforces the role that these mechanisms have in the aetiology of OC, as well as their reflection on the general conformation of the individual. These polymorphisms could be used in marker-assisted selection (MAS) programmes to improve desirable conformational traits, but taking into account their possible detrimental effect on OC prevalence.