Phosphate uptake in PhoX: Molecular mechanisms.

PhoX is a high-affinity phosphate binding protein, present in Xanthomonas citri, a phytopathogen responsible for the citrus canker disease. Performing molecular dynamics simulations and different types of computational analyses, we study the molecular mechanisms at play in relation to phosphate binding, revealing the global functioning of the protein: PhoX naturally oscillates along its global normal modes, which allow it to explore both bound and unbound conformations, eventually attracting a nearby negative phosphate ion to the highly positive electrostatic potential on its surface, particularly close to the binding pocket. There, several hydrogen bonds are formed with the two main domains of the structure. Phosphate creates, in this way, a strong bridge that connects the domains, keeping itself between them, in a tight closed conformation, explaining its high binding affinity.

Impact of oestrus synchronization devices on ewes vaginal microbiota and artificial insemination outcome.

Introduction: The low pregnancy rate by artificial insemination in sheep represents a fundamental challenge for breeding programs. In this species, oestrus synchronization is carried out by manipulating hormonal regimens through the insertion of progestogen intravaginal devices. This reproductive strategy may alter the vaginal microbiota affecting the artificial insemination outcome. Methods: In this study, we analyzed the vaginal microbiome of 94 vaginal swabs collected from 47 ewes with alternative treatments applied to the progesterone-releasing intravaginal devices (probiotic, maltodextrin, antibiotic and control), in two sample periods (before placing and after removing the devices). To our knowledge, this is the first study using nanopore-based metagenome sequencing for vaginal microbiome characterization in livestock. Results: Our results revealed a significant lower abundance of the genera Oenococcus (Firmicutes) and Neisseria (Proteobacteria) in pregnant compared to non-pregnant ewes. We also detected a significant lower abundance of Campylobacter in the group of samples treated with the probiotic. Discussion: Although the use of probiotics represents a promising practice to improve insemination results, the election of the suitable species and concentration requires further investigation. In addition, the use of progestogen in the synchronization devices seemed to increase the alpha-diversity and decrease the abundance of harmful microorganisms belonging to Gammaproteobacteria and Fusobacteriia classes, suggesting a beneficial effect of their use.

Intervenciones no farmacológicas orientadas a desórdenes en la alimentación en pediatría: un protocolo de revisión de alcance / Nonpharmacological interventions targeting feeding disorders in pediatrics: a scoping review protocol

Objetivo: proporcionar una visión general sobre la evidencia existente de las intervenciones no farmacológicas utilizadas en el tratamiento de niños, niñas y adolescentes con desafíos en la alimentación. Métodos: el protocolo se basa en el marco esbozado por Arksey y O'Malley. Las bases de datos en las que se buscará son: MEDLINE (PubMed), SciELO, LILACS y literatura gris. La revisión considerará los estudios que incluyan a pacientes menores de 18 años que tengan trastornos alimentarios, independientemente del diagnóstico, y que hayan participado en intervenciones no farmacológicas proporcionadas por cualquier profesional sanitario. Los datos se extraerán mediante una herramienta de extracción de datos que incluya detalles específicos sobre la población, el concepto, el contexto, los métodos de estudio y los resultados clave relevantes para el objetivo de la revisión. Conclusión: la revisión de alcance planeada será el primer esfuerzo para describir las intervenciones no farmacológicas para niños con desafíos en la alimentación. Los resultados del estudio proporcionarán una base de lo que existe y de lo que aún está por desarrollarse, beneficiando a los profesionales de la salud para desarrollar y/o mejorar su actual trabajo diario. (AU)

Objective: To provide an overview over existing evidence of non- pharmacological interventions used in the treatment of children with feeding challenges. Methods: The protocol is based on the framework outlined by Arksey and O’Malley. Databases to be searched include MEDLINE (PubMed), SciELO, LILACS and gray literature . The review will consider studies that include children under 18 years of age who have eating disorders, regardless of diagnosis, and who participated in non- pharmacological interventions provided by any healthcare professional. Data will be extracted using a data extraction tool that includes specific details about the population, concept, setting, study methods, and key outcomes relevant to the purpose of the review. Conclusions: The planned scoping review will be the first effort to describe non- pharmacological interventions for children with eating disorders. The results of the study will provide a baseline of what exists and what is yet to be developed. This study could benefit health professionals to develop and/or improve their current daily work. (AU)

Detecting Local Adaptation between North and South European Atlantic Salmon Populations.

Pollution and other anthropogenic effects have driven a decrease in Atlantic salmon (Salmo salar) in the Iberian Peninsula. The restocking effort carried out in the 1980s, with salmon from northern latitudes with the aim of mitigating the decline of native populations, failed, probably due to the deficiency in adaptation of foreign salmon from northern Europe to the warm waters of the Iberian Peninsula. This result would imply that the Iberian populations of Atlantic salmon have experienced local adaptation in their past evolutionary history, as has been described for other populations of this species and other salmonids. Local adaptation can occur by divergent selections between environments, favoring the fixation of alleles that increase the fitness of a population in the environment it inhabits relative to other alleles favored in another population. In this work, we compared the genomes of different populations from the Iberian Peninsula (Atlantic and Cantabric basins) and Scotland in order to provide tentative evidence of candidate SNPs responsible for the adaptive differences between populations, which may explain the failures of restocking carried out during the 1980s. For this purpose, the samples were genotyped with a 220,000 high-density SNP array (Affymetrix) specific to Atlantic salmon. Our results revealed potential evidence of local adaptation for North Spanish and Scottish populations. As expected, most differences concerned the comparison of the Iberian Peninsula with Scotland, although there were also differences between Atlantic and Cantabric populations. A high proportion of the genes identified are related to development and cellular metabolism, DNA transcription and anatomical structure. A particular SNP was identified within the NADP-dependent malic enzyme-2 (mMEP-2*), previously reported by independent studies as a candidate for local adaptation in salmon from the Iberian Peninsula. Interestingly, the corresponding SNP within the mMEP-2* region was consistent with a genomic pattern of divergent selection.

Proteomic analysis of F1 hybrids and intermediate variants in a Littorina saxatilis hybrid zone.

Proteomic analysis was carried out on the Crab (upper-shore) and Wave (lower-shore) ecotypes of Littorina saxatilis from a hybrid zone at Silleiro Cape, Spain. Proteome profiles of individual snails were obtained. Protein expression in F1 hybrid snails bred in the laboratory and snails with intermediate shell phenotypes collected from the mid-shore were compared with Crab and Wave ecotypes using analytical approaches used to study dominance. Multivariate analysis over many protein spots showed that the F1 snails are distinct from both ecotypes but closer to the Wave ecotype. The intermediate snails are highly variable, some closer to the Crab and others to the Wave ecotype. Considered on a protein by protein basis, some proteins are significantly closer in expression to the Crab and others to the Wave ecotype for both F1 and intermediate snails. Furthermore, a significant majority of proteins were closer in expression to the Wave ecotype for the F1, consistent with the multivariate analysis. No such significant majority toward either the Crab or Wave ecotype was observed for the intermediate snails. The closer similarity of F1 and Wave ecotype expression patterns could be the result of similar selective pressures in the similar mid-shore and low-shore environments. For a significantly larger number of proteins, intermediate snails were closer in expression to the ecotype having the lower expression, for both Crab and Wave ecotypes. This is somewhat unexpected as lower expression might be expected to be an indication of impairment of function and lower fitness. Proteomic analysis could be important for the identification of candidate proteins useful for gaining improved understanding of adaptation and barriers to gene flow in hybrid zones.

Genomic patterns of homozygosity and inbreeding depression in Murciano-Granadina goats.

BACKGROUND: Inbreeding depression can adversely affect traits related to fitness, reproduction and productive performance. Although current research suggests that inbreeding levels are generally low in most goat breeds, the impact of inbreeding depression on phenotypes of economic interest has only been investigated in a few studies based on genealogical data. RESULTS: We genotyped 1040 goats with the Goat SNP50 BeadChip. This information was used to estimate different molecular inbreeding coefficients and characterise runs of homozygosity and homozygosity patterns. We detected 38 genomic regions with increased homozygosity as well as 8 ROH hotspots mapping to chromosomes 1, 2, 4, 6, 14, 16 and 17. Eight hundred seventeen goats with available records for dairy traits were analysed to evaluate the potential consequences of inbreeding depression on milk phenotypes. Four regions on chromosomes 8 and 25 were significantly associated with inbreeding depression for the natural logarithm of the somatic cell count. Notably, these regions contain several genes related with immunity, such as SYK, IL27, CCL19 and CCL21. Moreover, one region on chromosome 2 was significantly associated with inbreeding depression for milk yield. CONCLUSIONS: Although genomic inbreeding levels are low in Murciano-Granadina goats, significant evidence of inbreeding depression for the logarithm of the somatic cell count, a phenotype closely associated with udder health and milk yield, have been detected in this population. Minimising inbreeding would be expected to augment economic gain by increasing milk yield and reducing the incidence of mastitis, which is one of the main causes of dairy goat culling.

[Use of ataluren in Spain: administrative incoherences and ethical implications]. / Uso de ataluren en España: incoherencias administrativas y aspectos éticos implicados.

Duchenne muscular dystrophy is a rare genetic disease with only ataluren like pharmaceutical treatment available. This drug received a conditional authorization by the European Medicines Agency (EMA) in 2014, meaning that it was commercially available while waiting for more solid results that demonstrate the efficacy and safety. Currently, the authorization still maintains the ″conditional″ modality, and the actual health benefits of the drug still remain unclear. In Spain, ataluren is not financed by the National Health System. The decision of non-financing has generated a heated debate, especially because in those patients who se treatment were started prior to the non-financing decision the drug has continued being funded. This controversial situation encompasses complex aspects of pharmaceutical and health management related to scientific evidence, the motivations of regulatory agencies and the pharmaceutical industry in the processes of drug investigation and authorization. Furthermore, as the center of the debate, some pillars of bioethics such as justice and equity, as well as certain legal principles, such as the protection of minors, are involved.

Estimates of recent and historical effective population size in turbot, seabream, seabass and carp selective breeding programmes.

BACKGROUND: The high fecundity of fish species allows intense selection to be practised and therefore leads to fast genetic gains. Based on this, numerous selective breeding programmes have been started in Europe in the last decades, but in general, little is known about how the base populations of breeders have been built. Such knowledge is important because base populations can be created from very few individuals, which can lead to small effective population sizes and associated reductions in genetic variability. In this study, we used genomic information that was recently made available for turbot (Scophthalmus maximus), gilthead seabream (Sparus aurata), European seabass (Dicentrarchus labrax) and common carp (Cyprinus carpio) to obtain accurate estimates of the effective size for commercial populations. METHODS: Restriction-site associated DNA sequencing data were used to estimate current and historical effective population sizes. We used a novel method that considers the linkage disequilibrium spectrum for the whole range of genetic distances between all pairs of single nucleotide polymorphisms (SNPs), and thus accounts for potential fluctuations in population size over time. RESULTS: Our results show that the current effective population size for these populations is small (equal to or less than 50 fish), potentially putting the sustainability of the breeding programmes at risk. We have also detected important drops in effective population size about five to nine generations ago, most likely as a result of domestication and the start of selective breeding programmes for these species in Europe. CONCLUSIONS: Our findings highlight the need to broaden the genetic composition of the base populations from which selection programmes start, and suggest that measures designed to increase effective population size within all farmed populations analysed here should be implemented in order to manage genetic variability and ensure the sustainability of the breeding programmes.

The value of genomic relationship matrices to estimate levels of inbreeding.

BACKGROUND: Genomic relationship matrices are used to obtain genomic inbreeding coefficients. However, there are several methodologies to compute these matrices and there is still an unresolved debate on which one provides the best estimate of inbreeding. In this study, we investigated measures of inbreeding obtained from five genomic matrices, including the Nejati-Javaremi allelic relationship matrix (FNEJ), the Li and Horvitz matrix based on excess of homozygosity (FL&H), and the VanRaden (methods 1, FVR1, and 2, FVR2) and Yang (FYAN) genomic relationship matrices. We derived expectations for each inbreeding coefficient, assuming a single locus model, and used these expectations to explain the patterns of the coefficients that were computed from thousands of single nucleotide polymorphism genotypes in a population of Iberian pigs. RESULTS: Except for FNEJ, the evaluated measures of inbreeding do not match with the original definitions of inbreeding coefficient of Wright (correlation) or Malécot (probability). When inbreeding coefficients are interpreted as indicators of variability (heterozygosity) that was gained or lost relative to a base population, both FNEJ and FL&H led to sensible results but this was not the case for FVR1, FVR2 and FYAN. When variability has increased relative to the base, FVR1, FVR2 and FYAN can indicate that it decreased. In fact, based on FYAN, variability is not expected to increase. When variability has decreased, FVR1 and FVR2 can indicate that it has increased. Finally, these three coefficients can indicate that more variability than that present in the base population can be lost, which is also unreasonable. The patterns for these coefficients observed in the pig population were very different, following the derived expectations. As a consequence, the rate of inbreeding depression estimated based on these inbreeding coefficients differed not only in magnitude but also in sign. CONCLUSIONS: Genomic inbreeding coefficients obtained from the diagonal elements of genomic matrices can lead to inconsistent results in terms of gain and loss of genetic variability and inbreeding depression estimates, and thus to misleading interpretations. Although these matrices have proven to be very efficient in increasing the accuracy of genomic predictions, they do not always provide a useful measure of inbreeding.

Recent Demographic History Inferred by High-Resolution Analysis of Linkage Disequilibrium.

Inferring changes in effective population size (Ne) in the recent past is of special interest for conservation of endangered species and for human history research. Current methods for estimating the very recent historical Ne are unable to detect complex demographic trajectories involving multiple episodes of bottlenecks, drops, and expansions. We develop a theoretical and computational framework to infer the demographic history of a population within the past 100 generations from the observed spectrum of linkage disequilibrium (LD) of pairs of loci over a wide range of recombination rates in a sample of contemporary individuals. The cumulative contributions of all of the previous generations to the observed LD are included in our model, and a genetic algorithm is used to search for the sequence of historical Ne values that best explains the observed LD spectrum. The method can be applied from large samples to samples of fewer than ten individuals using a variety of genotyping and DNA sequencing data: haploid, diploid with phased or unphased genotypes and pseudohaploid data from low-coverage sequencing. The method was tested by computer simulation for sensitivity to genotyping errors, temporal heterogeneity of samples, population admixture, and structural division into subpopulations, showing high tolerance to deviations from the assumptions of the model. Computer simulations also show that the proposed method outperforms other leading approaches when the inference concerns recent timeframes. Analysis of data from a variety of human and animal populations gave results in agreement with previous estimations by other methods or with records of historical events.

Identification of genomic regions regulating sex determination in Atlantic salmon using high density SNP data.

BACKGROUND: A complete understanding of the genetic basis for sexual determination and differentiation is necessary in order to implement efficient breeding schemes at early stages of development. Atlantic salmon belongs to the family Salmonidae of fishes and represents a species of great commercial value. Although the species is assumed to be male heterogametic with XY sex determination, the precise genetic basis of sexual development remains unclear. The complexity is likely associated to the relatively recent salmonid specific whole genome duplication that may be responsible for certain genome instability. This instability together with the capacity of the sex-determining gene to move across the genome as reported by previous studies, may explain that sexual development genes are not circumscribed to the same chromosomes in all members of the species. In this study, we have used a 220 K SNP panel developed for Atlantic salmon to identify the chromosomes explaining the highest proportion of the genetic variance for sex as well as candidate regions and genes associated to sexual development in this species. RESULTS: Results from regional heritability analysis showed that the chromosomes explaining the highest proportion of variance in these populations were Ssa02 (heritability = 0.42, SE = 0.12) and Ssa21 (heritability = 0.26, SE = 0.11). After pruning by linkage disequilibrium, genome-wide association analyses revealed 114 SNPs that were significantly associated with sex, being Ssa02 the chromosome containing a greatest number of regions. Close examination of the candidate regions evidenced important genes related to sex in other species of Class Actinopterygii, including SDY, genes from family SOX, RSPO1, ESR1, U2AF2A, LMO7, GNRH-R, DND and FIGLA. CONCLUSIONS: The combined results from regional heritability analysis and genome-wide association have provided new advances in the knowledge of the genetic regulation of sex determination in Atlantic salmon, supporting that Ssa02 is the candidate chromosome for sex in this species and suggesting an alternative population lineage in Spanish wild populations according to the results from Ssa21.

Disentangling Genetic Variation for Resistance and Endurance to Scuticociliatosis in Turbot Using Pedigree and Genomic Information.

Selective breeding for improving host responses to infectious pathogens is a promising option for disease control. In fact, disease resilience, the ability of a host to survive or cope with infectious challenge, has become a highly desirable breeding goal. However, resilience is a complex trait composed of two different host defence mechanisms, namely resistance (the ability of a host to avoid becoming infected or diseased) and endurance (the ability of an infected host to survive the infection). While both could be targeted for genetic improvement, it is currently unknown how they contribute to survival, as reliable estimates of genetic parameters for both traits obtained simultaneously are scarce. A difficulty lies in obtaining endurance phenotypes for genetic analyses. In this study, we present the results from an innovative challenge test carried out in turbot whose design allowed disentangling the genetic basis of resistance and endurance to Philasterides dicentrarchi, a parasite causing scuticociliatosis that leads to substantial economic losses in the aquaculture industry. A noticeable characteristic of the parasite is that it causes visual signs that can be used for disentangling resistance and endurance. Our results showed the existence of genetic variation for both traits (heritability = 0.26 and 0.12 for resistance and endurance, respectively) and for the composite trait resilience (heritability = 0.15). The genetic correlation between resistance and resilience was very high (0.90) indicating that both are at a large extent the same trait, but no significant genetic correlation was found between resistance and endurance. A total of 18,125 SNPs obtained from 2b-RAD sequencing enabled genome-wide association analyses for detecting QTLs controlling the three traits. A candidate QTL region on linkage group 19 that explains 33% of the additive genetic variance was identified for resilience. The region contains relevant genes related to immune response and defence mechanisms. Although no significant associations were found for resistance, the pattern of association was the same as for resilience. For endurance, one significant association was found on linkage group 2. The accuracy of genomic breeding values was also explored for resilience, showing that it increased by 12% when compared with the accuracy of pedigree-based breeding values. To our knowledge, this is the first study in turbot disentangling the genetic basis of resistance and endurance to scuticociliatosis.

Genetic differences in host infectivity affect disease spread and survival in epidemics.

Survival during an epidemic is partly determined by host genetics. While quantitative genetic studies typically consider survival as an indicator for disease resistance (an individual's propensity to avoid becoming infected or diseased), mortality rates of populations undergoing an epidemic are also affected by endurance (the propensity of diseased individual to survive the infection) and infectivity (i.e. the propensity of an infected individual to transmit disease). Few studies have demonstrated genetic variation in disease endurance, and no study has demonstrated genetic variation in host infectivity, despite strong evidence for considerable phenotypic variation in this trait. Here we propose an experimental design and statistical models for estimating genetic diversity in all three host traits. Using an infection model in fish we provide, for the first time, direct evidence for genetic variation in host infectivity, in addition to variation in resistance and endurance. We also demonstrate how genetic differences in these three traits contribute to survival. Our results imply that animals can evolve different disease response types affecting epidemic survival rates, with important implications for understanding and controlling epidemics.

Population genomics of parallel evolution in gene expression and gene sequence during ecological adaptation.

Natural selection often produces parallel phenotypic changes in response to a similar adaptive challenge. However, the extent to which parallel gene expression differences and genomic divergence underlie parallel phenotypic traits and whether they are decoupled or not remains largely unexplored. We performed a population genomic study of parallel ecological adaptation among replicate ecotype pairs of the rough periwinkle (Littorina saxatilis) at a regional geographical scale (NW Spain). We show that genomic changes underlying parallel phenotypic divergence followed a complex pattern of both repeatable differences and of differences unique to specific ecotype pairs, in which parallel changes in expression or sequence are restricted to a limited set of genes. Yet, the majority of divergent genes were divergent either for gene expression or coding sequence, but not for both simultaneously. Overall, our findings suggest that divergent selection significantly contributed to the process of parallel molecular differentiation among ecotype pairs, and that changes in expression and gene sequence underlying phenotypic divergence could, at least to a certain extent, be considered decoupled processes.

Historical Biogeography of the Marine Snail Littorina saxatilis Inferred from Haplotype and Shell Morphology Evolution in NW Spain.

The marine snail Littorina saxatilis exhibits extreme morphological variation between and within geographical regions and represents an excellent model for assessing local adaptation. Previous studies support the hypothesis of parallel evolution in sympatry of two morphologically different ecotypes (named as RB and SU) that co-inhabit different habitats from Galician rocky shores (NW Spain), and which are interrupted by sheltered areas inhabited by a different morph never studied before (named as SRB). Here, we use morphological and mitochondrial DNA (mtDNA) sequence data to test hypotheses on the origin and diversification of SRB snails and to assess their evolutionary relationships with RB and SU ecotypes. Our results show that the SRB morph displays the largest size and shell elongation and the smallest relative shell aperture, representing an extreme type of the RB vs. SU polymorphism, which has been linked to adaptation to sheltered ecological factors. Phylogenetic analysis shows that the SRB morph shares ancestry with RB and SU ecotypes, rejecting the hypothesis that the SRB morph marks relict populations from which these ecotypes evolved in Galician coasts. Our data support that genetic differentiation among SRB, RB and SU morphs results from a general pattern of restricted gene flow and isolation by distance linked to the colonization of Galician coasts by two independent mtDNA lineages, rather than from a random fragmentation of the initial distributional range. Therefore, the confinement of distinct lineages to specific geographical areas denote evident limits to the distances these snails can disperse. Morphological analysis indicates no association between mtDNA lineage and a specific morphotype, and suggests the independent gain of convergent morphological patterns within each mtDNA lineage in populations occupying contrasting habitats following the colonization of Galician coasts.

Evaluation of the linkage-disequilibrium method for the estimation of effective population size when generations overlap: an empirical case.

BACKGROUND: Within the genetic methods for estimating effective population size (N e ), the method based on linkage disequilibrium (LD) has advantages over other methods, although its accuracy when applied to populations with overlapping generations is a matter of controversy. It is also unclear the best way to account for mutation and sample size when this method is implemented. Here we have addressed the applicability of this method using genome-wide information when generations overlap by profiting from having available a complete and accurate pedigree from an experimental population of Iberian pigs. Precise pedigree-based estimates of N e were considered as a baseline against which to compare LD-based estimates. METHODS: We assumed six different statistical models that varied in the adjustments made for mutation and sample size. The approach allowed us to determine the most suitable statistical model of adjustment when the LD method is used for species with overlapping generations. A novel approach used here was to treat different generations as replicates of the same population in order to assess the error of the LD-based N e estimates. RESULTS: LD-based N e estimates obtained by estimating the mutation parameter from the data and by correcting sample size using the 1/2n term were the closest to pedigree-based estimates. The N e at the time of the foundation of the herd (26 generations ago) was 20.8 ± 3.7 (average and SD across replicates), while the pedigree-based estimate was 21. From that time on, this trend was in good agreement with that followed by pedigree-based N e. CONCLUSIONS: Our results showed that when using genome-wide information, the LD method is accurate and broadly applicable to small populations even when generations overlap. This supports the use of the method for estimating N e when pedigree information is unavailable in order to effectively monitor and manage populations and to early detect population declines. To our knowledge this is the first study using replicates of empirical data to evaluate the applicability of the LD method by comparing results with accurate pedigree-based estimates.

Does DNA methylation regulate metamorphosis? The case of the sea lamprey (Petromyzon marinus) as an example.

Lampreys represent one of the most ancient vertebrate lineages enclosing a special interest for genetic and epigenetic studies. The sea lamprey (Petromyzon marinus) is an anadromous species that experiences metamorphosis all the way up to the adult stage. Although representing a gradual process, metamorphosis in this species involves dramatic conversions with regard to physiological together with structural body changes preparing individuals for a marine and parasitic life; in consequence, multiple gene expression modifications are expected. The implications of thyroid hormones and HOX gene expression changes have previously been reported in this species and also in other vertebrate species. Nonetheless, information lacks on how these genes are regulated in lampreys. We here report about the existence of methylation pattern differences between the adult and the larvae sea lamprey life cycle stages making use of the Methylation-Sensitive Amplified Polymorphism (MSAP) technique. Differentially methylated fragment sequencing allowed to establish homologous identities with HOX genes involved in morphogenesis, along with genes related to the water balance and to the osmotic homoeostasis, all associated to a marine environment adaptation. These results provide evidences revealing that DNA methylation plays a role in the epigenetic regulation of the P. marinus post-natal development representing a starting point for future studies. To the best of our knowledge, this is the first study which detects DNA methylation changes associated with metamorphosis in lampreys.

Detecting inbreeding depression for reproductive traits in Iberian pigs using genome-wide data.

BACKGROUND: The current availability of genotypes for very large numbers of single nucleotide polymorphisms (SNPs) is leading to more accurate estimates of inbreeding coefficients and more detailed approaches for detecting inbreeding depression. In the present study, genome-wide information was used to detect inbreeding depression for two reproductive traits (total number of piglets born and number of piglets born alive) in an ancient strain of Iberian pigs (the Guadyerbas strain) that is currently under serious danger of extinction. METHODS: A total of 109 sows with phenotypic records were genotyped with the PorcineSNP60 BeadChip v1. Inbreeding depression was estimated using a bivariate animal model in which the inbreeding coefficient was included as a covariate. We used two different measures of genomic inbreeding to perform the analyses: inbreeding estimated on a SNP-by-SNP basis and inbreeding estimated from runs of homozygosity. We also performed the analyses using pedigree-based inbreeding. RESULTS: Significant inbreeding depression was detected for both traits using all three measures of inbreeding. Genome-wide information allowed us to identify one region on chromosome 13 associated with inbreeding depression. This region spans from 27 to 54 Mb and overlaps with a previously detected quantitative trait locus and includes the inter-alpha-trypsin inhibitor gene cluster that is involved with embryo implantation. CONCLUSIONS: Our results highlight the value of high-density SNP genotyping for providing new insights on where genes causing inbreeding depression are located in the genome. Genomic measures of inbreeding obtained on a SNP-by-SNP basis or those based on the presence/absence of runs of homozygosity represent a suitable alternative to pedigree-based measures to detect inbreeding depression, and a useful tool for mapping studies. To our knowledge, this is the first study in domesticated animals using the SNP-by-SNP inbreeding coefficient to map specific regions within chromosomes associated with inbreeding depression.