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

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. 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. 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

A protein-coding gene expression atlas from the brain of pregnant and non-pregnant goats

Background: The brain is an extraordinarily complex organ with multiple anatomical structures involved in highly specialized functions related with behavior and physiological homeostasis. Our goal was to build an atlas of protein-coding gene expression in the goat brain by sequencing the transcriptomes of 12 brain regions in seven female Murciano-Granadina goats, from which three of them were 1-month pregnant. Results: Between 14,889 (cerebellar hemisphere) and 15,592 (pineal gland) protein-coding genes were expressed in goat brain regions, and most of them displayed ubiquitous or broad patterns of expression across tissues. Principal component analysis and hierarchical clustering based on the patterns of mRNA expression revealed that samples from certain brain regions tend to group according to their position in the anterior-posterior axis of the neural tube, i.e., hindbrain (pons and medulla oblongata), midbrain (rostral colliculus) and forebrain (frontal neocortex, olfactory bulb, hypothalamus, and hippocampus). Exceptions to this observation were cerebellum and glandular tissues (pineal gland and hypophysis), which showed highly divergent mRNA expression profiles. Differential expression analysis between pregnant and non-pregnant goats revealed moderate changes of mRNA expression in the frontal neocortex, hippocampus, adenohypophysis and pons, and very dramatic changes in the olfactory bulb. Many genes showing differential expression in this organ are related to olfactory function and behavior in humans. Conclusion: With the exception of cerebellum and glandular tissues, there is a relationship between the cellular origin of sampled regions along the anterior-posterior axis of the neural tube and their mRNA expression patterns in the goat adult brain. Gestation induces substantial changes in the mRNA expression of the olfactory bulb, a finding consistent with the key role of this anatomical structure on the development of maternal behavior

A protein-coding gene expression atlas from the brain of pregnant and non-pregnant goats

[Background] The brain is an extraordinarily complex organ with multiple anatomical structures involved in highly specialized functions related with behavior and physiological homeostasis. Our goal was to build an atlas of protein-coding gene expression in the goat brain by sequencing the transcriptomes of 12 brain regions in seven female Murciano-Granadina goats, from which three of them were 1-month pregnant.[Results] Between 14,889 (cerebellar hemisphere) and 15,592 (pineal gland) protein-coding genes were expressed in goat brain regions, and most of them displayed ubiquitous or broad patterns of expression across tissues. Principal component analysis and hierarchical clustering based on the patterns of mRNA expression revealed that samples from certain brain regions tend to group according to their position in the anterior-posterior axis of the neural tube, i.e., hindbrain (pons and medulla oblongata), midbrain (rostral colliculus) and forebrain (frontal neocortex, olfactory bulb, hypothalamus, and hippocampus). Exceptions to this observation were cerebellum and glandular tissues (pineal gland and hypophysis), which showed highly divergent mRNA expression profiles. Differential expression analysis between pregnant and non-pregnant goats revealed moderate changes of mRNA expression in the frontal neocortex, hippocampus, adenohypophysis and pons, and very dramatic changes in the olfactory bulb. Many genes showing differential expression in this organ are related to olfactory function and behavior in humans.[Conclusion] With the exception of cerebellum and glandular tissues, there is a relationship between the cellular origin of sampled regions along the anterior-posterior axis of the neural tube and their mRNA expression patterns in the goat adult brain. Gestation induces substantial changes in the mRNA expression of the olfactory bulb, a finding consistent with the key role of this anatomical structure on the development of maternal behavior.This research was funded by the European Regional Development Fund (FEDER)/Ministerio de Ciencia e Innovación—Agencia Estatal de Investigación/Project Reference grants: AGL2016-76108-R and also by project PID2019-105805RB-I00 funded by MCIN/AEI/10.13039/501100011033. We also acknowledge the support of the CERCA Programme/Generalitat de Catalunya and of the Spanish Ministry of Economy and Competitivity for the Center of Excellence Severo Ochoa 2020-2023 (CEX2019-000902-S) grant awarded to the Centre for Research in Agricultural Genomics (CRAG, Bellaterra, Spain). Maria Luigi-Sierra was funded with a PhD fellowship “Formación de Personal Investigador” (BES-2017-079709) awarded by the Spanish Ministry of Economy and Competitivity and by “ESF Investing in your future”. Dailu Guan was funded by a PhD fellowship from the China Scholarship Council (CSC). Emilio Mármol-Sánchez was funded with a FPU Ph.D. grant from the Spanish Ministry of Education (FPU15/01733).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000902-S)Peer reviewe

A protein-coding gene expression atlas from the brain of pregnant and non-pregnant goats

Background: The brain is an extraordinarily complex organ with multiple anatomical structures involved in highly specialized functions related with behavior and physiological homeostasis. Our goal was to build an atlas of protein-coding gene expression in the goat brain by sequencing the transcriptomes of 12 brain regions in seven female Murciano-Granadina goats, from which three of them were 1-month pregnant.Results: Between 14,889 (cerebellar hemisphere) and 15,592 (pineal gland) protein-coding genes were expressed in goat brain regions, and most of them displayed ubiquitous or broad patterns of expression across tissues. Principal component analysis and hierarchical clustering based on the patterns of mRNA expression revealed that samples from certain brain regions tend to group according to their position in the anterior-posterior axis of the neural tube, i.e., hindbrain (pons and medulla oblongata), midbrain (rostral colliculus) and forebrain (frontal neocortex, olfactory bulb, hypothalamus, and hippocampus). Exceptions to this observation were cerebellum and glandular tissues (pineal gland and hypophysis), which showed highly divergent mRNA expression profiles. Differential expression analysis between pregnant and non-pregnant goats revealed moderate changes of mRNA expression in the frontal neocortex, hippocampus, adenohypophysis and pons, and very dramatic changes in the olfactory bulb. Many genes showing differential expression in this organ are related to olfactory function and behavior in humans.Conclusion: With the exception of cerebellum and glandular tissues, there is a relationship between the cellular origin of sampled regions along the anterior-posterior axis of the neural tube and their mRNA expression patterns in the goat adult brain. Gestation induces substantial changes in the mRNA expression of the olfactory bulb, a finding consistent with the key role of this anatomical structure on the development of maternal behavior

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Variability in porcine microRNA genes and its association with mRNA expression and lipid phenotypes

Background: Mature microRNAs (miRNAs) play an important role in repressing the expression of a wide range of mRNAs. The presence of polymorphic sites in miRNA genes and their corresponding 3'UTR binding sites can disrupt canonical conserved miRNA-mRNA pairings, and thus modify gene expression patterns. However, to date such polymorphic sites in miRNA genes and their association with gene expression phenotypes and complex traits are poorly characterized in pigs. Results: By analyzing whole-genome sequences from 120 pigs and wild boars from Europe and Asia, we identified 285 single nucleotide polymorphisms (SNPs) that map to miRNA loci, and 109,724 SNPs that are located in predicted 7mer-m8 miRNA binding sites within porcine 3'UTR. In porcine miRNA genes, SNP density is reduced compared with their flanking non-miRNA regions. By sequencing the genomes of five Duroc boars, we identified 12 miRNA SNPs that were subsequently genotyped in their offspring (N = 345, Lipgen population). Association analyses of miRNA SNPs with 38 lipid-related traits and hepatic and muscle microarray expression phenotypes recorded in the Lipgen population were performed. The most relevant detected association was between the genotype of the rs319154814 (G/A) SNP located in the apical loop of the ssc-miR-326 hairpin precursor and PPP1CC mRNA levels in the liver (q-value = 0.058). This result was subsequently confirmed by qPCR (P-value = 0.027). The rs319154814 (G/A) genotype was also associated with several fatty acid composition traits. Conclusions: Our findings show a reduced variability of porcine miRNA genes, which is consistent with strong purifying selection, particularly in the seed region that plays a critical role in miRNA binding. Although it is generally assumed that SNPs mapping to the seed region are those with the most pronounced consequences on mRNA expression, we show that a SNP mapping to the apical region of ssc-miR-326 is significantly associated with hepatic mRNA levels of the PPP1CC gene, one of its predicted targets. Although experimental confirmation of such an interaction is reported in humans but not in pigs, this result highlights the need to further investigate the functional effects of miRNA polymorphisms that are located outside the seed region on gene expression in pigs.The research presented in the current publication was funded by Grants AGL2013-48742-C2-1-R and AGL2013-48742-C2-2-R awarded by the Spanish Ministry of Economy and Competitivity. We also acknowledge the support of the Spanish Ministry of Science and Innovation for the Center of Excellence Severo Ochoa 2020–2023 (CEX2019-000902-S) grant awarded to the Centre for Research in Agricultural Genomics (CRAG, Bellaterra, Spain). Emilio Mármol-Sánchez was funded by a FPU Ph.D. grant from the Spanish Ministry of Education (FPU15/01733). María Gracia Luigi-Sierra was funded with a Ph.D. fellowship “Formación de Personal Investigador” (BES-C-2017-0024) awarded by the Spanish Ministry of Economy and Competitivity. Dailu Guan was funded by a Ph.D. fellowship from the Scholarship Council of China (CSC). The authors thank the CERCA Programme of the Generalitat de Catalunya (Barcelona, Spain) for their support and those who provided publicly available dat

Assessing the levels of intraspecific admixture and interspecific hybridization in Iberian wild goats (Capra pyrenaica)

Iberian wild goats (Capra pyrenaica, also known as Iberian ibex, Spanish ibex, and Spanish wild goat) underwent strong genetic bottlenecks during the 19th and 20th centuries due to overhunting and habitat destruction. From the 1970s to 1990s, augmentation translocations were frequently carried out to restock Iberian wild goat populations (very often with hunting purposes), but they were not systematically planned or recorded. On the other hand, recent data suggest the occurrence of hybridization events between Iberian wild goats and domestic goats (Capra hircus). Augmentation translocations and interspecific hybridization might have contributed to increase the diversity of Iberian wild goats. With the aim of investigating this issue, we have genotyped 118 Iberian wild goats from Tortosa-Beceite, Sierra Nevada, Muela de Cortes, Gredos, Batuecas and, Ordesa and Monte Perdido by using the Goat SNP50 BeadChip (Illumina). The analysis of genotypic data indicated that Iberian wild goat populations are strongly differentiated and display low diversity. Only three Iberian wild goats out from 118 show genomic signatures of mixed ancestry, a result consistent with a scenario in which past augmentation translocations have had a limited impact on the diversity of Iberian wild goats. Besides, we have detected eight Iberian wild goats from Tortosa-Beceite with signs of domestic goat introgression. Although rare, hybridization with domestic goats could become a potential threat to the genetic integrity of Iberian wild goats, hence measures should be taken to avoid the presence of uncontrolled herds of domestic or feral goats in mountainous areas inhabited by this iconic wild ungulate.Publishe

Introgression with domestic goats has expanded the genetic variability of the Spanish ibex

Resumen del póster presentado a la 37th International Conference on Animal Genetics (ISAG), celebrada en Lleida (España) del 7 al 12 de julio de 2019.The Spanish ibex (Capra pyrenaica) is a wild goat species distributed in the Iberian Peninsula. Based on phenotypic criteria, 4 subspecies have been defined: C. p. hispanica (CPH, south and east of the Iberian Peninsula), C. p. victoriae (CPV, center and northwest of the Iberian Peninsula), C. p. lusitanica (CPL, Galicia and north of Portugal) and C. p. pyrenaica (CPP, Pyrenees mountains). Hunting, epidemics and habitat loss caused the extinction of CPL (disappeared in the 19th century) and CPP (extinct in the year 2000) as well as severe population bottlenecks decreasing the diversity of CPV and CPH. By using a high throughput genotyping approach, we have demonstrated that interspecific hybridization with domestic goats has been an important source of novel variability for Spanish ibexes living in Tortosa-Beceite. Individual sequencing of one of the last CPP representatives ( × 16.6 coverage) and Pool-sequencing ( × 39 coverage) of 30 CPH and 23 CPV individuals revealed an extensive sharing of SNPs (96%) between the CPP individual and the extant CPV and CPH subspecies, thus suggesting that the extinction of CPP did not cause a major loss of diversity in Capra pyrenaica. Sequencing experiments also revealed that the genome of one of the last CPP representatives contains stop-gained mutations, with heterozygous genotypes, in the WASF2, RBM17 and SERPINB10 genes. The inactivation of WASF2 and RBM17 causes embryonic lethality, while SERPINB10 belongs to a family of serin proteases with key roles in immunity and other biological processes. Our results suggest that the dramatic reduction of the CPP population during the19th-20th centuries led to the progressive accumulation of mutations with harmful effects (genomic meltdown) that probably contributed to its extinction by limiting fitness and reproductive success

Genetic Diversity of Bubalus bubalis in Germany and Global Relations of Its Genetic Background

This is the first study to explore the genetic diversity and population structure of domestic water buffalo (Bubalus bubalis) in Germany and their potential relations to herds in other parts of Europe or worldwide. To this end, animals from different herds in Germany, Bulgaria, Romania, and Hungary were genotyped and compared to genotypes from other populations with worldwide distribution and open to the public. The pilot study analyzed population structure, phylogenetic tree, and inbreeding events in our samples. In buffalos from Germany, a mixed genetic make-up with contributions from Bulgaria (Murrah breed), Romania, and Italy was found. All in all, a high degree of genetic diversity was identified in European buffalos, and a novel genotype was described in Hungarian buffalos by this study. We demonstrate that European buffalos stand out from other buffalo populations worldwide, supporting the idea that buffalos have not completely disappeared from the European continent during the late Pleistocene. The high genetic diversity in European buffalos seems to be an excellent prerequisite for the establishment of local breeds characterized by unique traits and features. This study may also be considered as an initial step on the way to genome characterization for the sustainable development of the buffalo economy in Germany and other parts of Europe in the future.</p

Assessing the levels of intraspecific admixture and interspecific hybridization in Iberian wild goats (Capra pyrenaica)

Iberian wild goats (Capra pyrenaica, also known as Iberian ibex, Spanish ibex, and Spanish wild goat) underwent strong genetic bottlenecks during the 19th and 20th centuries due to overhunting and habitat destruction. From the 1970s to 1990s, augmentation translocations were frequently carried out to restock Iberian wild goat populations (very often with hunting purposes), but they were not systematically planned or recorded. On the other hand, recent data suggest the occurrence of hybridization events between Iberian wild goats and domestic goats (Capra hircus). Augmentation translocations and interspecific hybridization might have contributed to increase the diversity of Iberian wild goats. With the aim of investigating this issue, we have genotyped 118 Iberian wild goats from Tortosa-Beceite, Sierra Nevada, Muela de Cortes, Gredos, Batuecas, and Ordesa and Monte Perdido by using the Goat SNP50 BeadChip (Illumina). The analysis of genotypic data indicated that Iberian wild goat populations are strongly differentiated and display low diversity. Only three Iberian wild goats out from 118 show genomic signatures of mixed ancestry, a result consistent with a scenario in which past augmentation translocations have had a limited impact on the diversity of Iberian wild goats. Besides, we have detected eight Iberian wild goats from Tortosa-Beceite with signs of domestic goat introgression. Although rare, hybridization with domestic goats could become a potential threat to the genetic integrity of Iberian wild goats; hence, measures should be taken to avoid the presence of uncontrolled herds of domestic or feral goats in mountainous areas inhabited by this iconic wild ungulate.This research was funded by the European Regional Development Fund (FEDER)/Ministerio de Ciencia e Innovaci?n?Agencia Estatal de Investigaci?n/Project Reference grant: PID2019-105805RB-I00 and by the CERCA Programme/Generalitat de Catalunya. We acknowledge the support of the Spanish Ministry of Economy and Competitiveness for the Center of Excellence Severo Ochoa 2020?2023 (CEX2019-000902-S) grant awarded to the Centre for Research in Agricultural Genomics (CRAG). We also acknowledge Jos? Folch, of the Centro de Investigaci?n y Tecnolog?a Agroalimentaria de Arag?n for his help in the development of his research. MGLS was funded with a FPI Ph.D. grant from the Spanish Ministry of Education (BES-C-2017-079079). TFC was funded with a fellowship from the CAPES Foundation-Coordination of Improvement of Higher Education, Ministry of Education of the Federal Government of Brazil. EMS was funded with a FPU Ph.D. grant from the Spanish Ministry of Education (FPU15/01733). GM is a Serra H?nter fellow (professor) of the Generalitat de Catalunya. Thanks also to the CERCA Programme of the Generalitat de Catalunya for their support. Sample collection benefitted from the research grants CGL2012-40043-C02-01, CGL2012-40043-C02-02, and CGL2016-80543-P, also from the Spanish Ministry of Economy and Competitiveness. Many thanks to Laura Botigu? for her help and assistance in carrying out the f3 tests of admixture