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Abstract The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided little support for the currently described four subspecies. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.

Abstract Background The genomes of indigenous African cattle are composed of components with Middle Eastern (taurine) and South Asian (indicine) origins, providing a valuable model to study hybridization and to identify genetic barriers to gene flow. In this study, we analysed indigenous African cattle breeds as models of hybrid zones, considering taurine and indicine samples as ancestors. In a genomic cline analysis of whole-genome sequence data, we considered over 8 million variants from 144 animals, which allows for fine-mapping of potential genomic incompatibilities at high resolution across the genome. Results We identified several thousand variants that had significantly steep clines (‘SCV’) across the whole genome, indicating restricted introgression. Some of the SCV were clustered into extended regions, with the longest on chromosome 7, spanning 725 kb and including 27 genes. We found that variants with a high phenotypic impact (e.g. indels, intra-genic and missense variants) likely represent greater genetic barriers to gene flow. Furthermore, our findings provide evidence that a large proportion of breed differentiation in African cattle could be linked to genomic incompatibilities and reproductive isolation. Functional evaluation of genes with SCV suggest that mitonuclear incompatibilities and genes associated with fitness (e.g. resistance to paratuberculosis) could account for restricted gene flow in indigenous African cattle. Conclusions To our knowledge, this is the first time genomic cline analysis has been applied to identify restricted introgression in the genomes of indigenous African cattle and the results provide extended insights into mechanisms (e.g. genomic incompatibilities) contributing to hybrid differentiation. These results have important implications for our understanding of genetic incompatibilities and reproductive isolation and provide important insights into the impact of cross-breeding cattle with the aim of producing offspring that are both hardy and productive.

Abstract Background Understanding the variation between well and poorly adapted cattle breeds to local environments and pathogens is essential for breeding cattle with improved climate and disease-resistant phenotypes. Although considerable progress has been made towards identifying genetic differences between breeds, variation at the epigenetic and chromatin levels remains poorly characterized. Here, we generate, sequence and analyse over 150 libraries at base-pair resolution to explore the dynamics of DNA methylation and chromatin accessibility of the bovine immune system across three distinct cattle lineages. Results We find extensive epigenetic divergence between the taurine and indicine cattle breeds across immune cell types, which is linked to the levels of local DNA sequence divergence between the two cattle sub-species. The unique cell type profiles enable the deconvolution of complex cellular mixtures using digital cytometry approaches. Finally, we show distinct sub-categories of CpG islands based on their chromatin and methylation profiles that discriminate between classes of distal and gene proximal islands linked to discrete transcriptional states. Conclusions Our study provides a comprehensive resource of DNA methylation, chromatin accessibility and RNA expression profiles of three diverse cattle populations. The findings have important implications, from understanding how genetic editing across breeds, and consequently regulatory backgrounds, may have distinct impacts to designing effective cattle epigenome-wide association studies in non-European breeds.

Abstract Honey bee, Apis mellifera, drones are typically haploid, developing from an unfertilized egg, inheriting only their queen’s alleles and none from the many drones she mated with. Thus the ordered combination or ‘phase’ of alleles is known, making drones a valuable haplotype resource. We collated whole-genome sequence data for 1,407 drones, including 45 newly sequenced Scottish drones, collectively representing 19 countries, 8 subspecies and various hybrids. Following alignment to Amel_HAv3.1, variant calling and quality filtering, we retained 17.4 M high quality variants across 1,328 samples with a genotyping rate of 98.7%. We demonstrate the utility of this haplotype resource, AmelHap, for genotype imputation, returning >95% concordance when up to 61% of data is missing in haploids and up to 12% of data is missing in diploids. AmelHap will serve as a useful resource for the community for imputation from low-depth sequencing or SNP chip data, accurate phasing of diploids for association studies, and as a comprehensive reference panel for population genetic and evolutionary analyses.

The genus Plagyrona Gittenberger, 1977, includes only two small species of terrestrial snail: Plagyrona angusta Holyoak and Holyoak, 2012, and Plagyrona placida (Shuttleworth, 1852). While P. angusta is known only from Portugal, P. placida has a vast but fragmented distribution: it is known from some of the Macaronesian islands (Madeira and the Canary Archipelago) and some European countries: Portugal, France (in Corsica only), Italy (including Sardinia and the Tuscan Archipelago), Albania, Greece (in the Ionian Islands only) and North Africa (Algeria). New research has led to redefine the distribution range of P. angusta, identifying new populations in Spain (Balearic Islands), continental France (Var department), southern Italy (Campania), Sardinia and Greece (Kerkyra Island) and to discover new sites of P. placida on Pantelleria island and of Plagyrona spp. in Zannone island and southern Italy. The specific determination of these and others populations by examination of recent literature from Sardinia, Campania and Calabria, was carried out on a morphometric basis, but, for some populations, the variability of the diagnostic characters and the limited number of available specimens, do not allow a precise assignment. On the other hand, the existence of two distinct species is not evident at all, at least in the Mediterranean countries.

Measurement(s) Optical Mapping Technology Type(s) Optical Mapping Factor Type(s) Structural variants Sample Characteristic - Organism Bos taurus Sample Characteristic - Location United Kingdom • Kenya • Zambia • Uganda • Brazil • Nigeria

A wide spectrum of anomalies of the pancreas, the pancreatic ductal system and the biliary tree are commonly encountered at radiologic evaluation. Pancreas bifidum, also known as bifid pancreas or fish-tail pancreas, is an extremely rare congenital branching anomaly of the main pancreatic duct characterized by its duplication. These 2 separate ducts are laid from the pancreatic tail to neck and they generally join at the pancreas body-tail draining via the major papilla; the pancreatic parenchyma is also bifurcated with separated dorsal and caudal buds. The clinical impact of this condition is not well established: although some authors sustained that probably does not cause or contribute to abdominal pain or overt pancreatic diseases, others argued that could be considered as a possible cause of acute pancreatitis.We herewith describe the case of a 51-year-old woman presenting to our hospital with epigastric pain, nausea, and vomiting. Biochemical tests were suspicious for acute pancreatitis. Ultrasound examination was negative. MRI, including MR cholangiopancreatography revealed bifid pancreas characterized by duplication of the main pancreatic duct with 2 separate ducts that join at the pancreas head and draining via the minor papilla. On T2-weighted images the ventral bud of the pancreas was enlarged and characterized by slightly hyperintensity without peripancreatic fluid collections. The MRI findings were consistent with acute pancreatitis limited to the ventral bud of a bifid pancreas. Patient was treated with intravenous fluid resuscitation, pain control and institution of early enteral nutrition and discharged on the seventh day after admission.

An investigation of genetic variants that exist across human and livestock species supports the clear potential of livestock models in providing insights into the mechanisms driving human diseases and traits.

Abstract Background In cattle, genome-wide association studies (GWAS) have largely focused on European or Asian breeds, using genotyping arrays that were primarily designed for European cattle. Because there is growing interest in performing GWAS in African breeds, we have assessed the performance of 23 commercial bovine genotyping arrays for capturing the diversity across African breeds and performing imputation. We used 409 whole-genome sequences (WGS) spanning global cattle breeds, and a real cohort of 2481 individuals (including African breeds) that were genotyped with the Illumina high-density (HD) array and the GeneSeek bovine 50 k array. Results We found that commercially available arrays were not effective in capturing variants that segregate among African indicine animals. Only 6% of these variants in high linkage disequilibrium (LD) (r2 > 0.8) were on the best performing arrays, which contrasts with the 17% and 25% in African and European taurine cattle, respectively. However, imputation from available HD arrays can successfully capture most variants (accuracies up to 0.93), mainly when using a global, not continent-specific, reference panel, which partially reflects the unusually high levels of admixture on the continent. When considering functional variants, the GGPF250 array performed best for tagging WGS variants and imputation. Finally, we show that imputation from low-density arrays can perform almost as well as HD arrays, if a two-stage imputation approach is adopted, i.e. first imputing to HD and then to WGS, which can potentially reduce the costs of GWAS. Conclusions Our results show that the choice of an array should be based on a balance between the objective of the study and the breed/population considered, with the HD and BOS1 arrays being the best choice for both taurine and indicine breeds when performing GWAS, and the GGPF250 being preferable for fine-mapping studies. Moreover, our results suggest that there is no advantage to using the indicus-specific arrays for indicus breeds, regardless of the objective. Finally, we show that using a reference panel that better represents global bovine diversity improves imputation accuracy, particularly for non-European taurine populations.

We propose an AlGaAs microring resonator design for the generation of an optical frequency comb by means of the interplay between harmonic generation and Kerr effect. Modal phase matching imposes specific waveguide geometries and, consequently, it impacts the nonlinear efficiency of the system. We show the dynamics of χ(2) + χ(3) comb generation resulting from type-I modal phase matching.

Celiac disease (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. In rare cases, CD may occur with a severe potential life-threatening manifestation known as a celiac crisis (CC). This may be a consequence of a delayed diagnosis and expose patients to possible fatal complications. We report the case of a 22-month-old child admitted to our hospital for a CC characterized by weight loss, vomiting, and diarrhea associated with a malnutrition state. Early identification of symptoms of CC is essential to provide a prompt diagnosis and management.

Cattle reference genomes are valuable resources but are currently heavily biased towards European breeds. Here the authors integrate assemblies for African breeds into a more representative cattle graph genome capturing global breed diversity.

Abstract Background Climate and farming systems, several of which are considered as low-input agricultural systems, vary between goat populations from Northern and Southern Italy and have led to different management practices. These processes have impacted genome shaping in terms of inbreeding and regions under selection and resulted in differences between the northern and southern populations. Both inbreeding and signatures of selection can be pinpointed by the analysis of runs of homozygosity (ROH), which provides useful information to assist the management of this species in different rural areas. Results We analyzed the ROH distribution and inbreeding (F ROH) in 902 goats from the Italian Goat Consortium2 dataset. We evaluated the differences in individual ROH number and length between goat breeds from Northern (NRD) and Central-southern (CSD) Italy. Then, we identified the signatures of selection that differentiate these two groups using three methods: ROH, ΔROH, and averaged F ST. ROH analyses showed that some Italian goat breeds have a lower inbreeding coefficient, which is attributable to their management and history. ROH are longer in breeds that are undergoing non-optimal management or with small population size. In several small breeds, the ROH length classes are balanced, reflecting more accurate mating planning. The differences in climate and management between the NRD and CSD groups have resulted in different ROH lengths and numbers: the NRD populations bred in isolated valleys present more and shorter ROH segments, while the CSD populations have fewer and longer ROH, which is likely due to the fact that they have undergone more admixture events during the horizontal transhumance practice followed by a more recent standardization. We identified four genes within signatures of selection on chromosome 11 related to fertility in the NRD group, and 23 genes on chromosomes 5 and 6 related to growth in the CSD group. Finally, we identified 17 genes on chromosome 12 related to environmental adaptation and body size with high homozygosity in both groups. Conclusions These results show how different management practices have impacted the level of genomic inbreeding in two Italian goat groups and could be useful to assist management in a low-input system while safeguarding the diversity of small populations.

An appropriate use of natural resources, combined with the choice of innovative materials and the reduction of the consumption of non-renewable sources, increasingly contribute to the sustainability of skyscrapers. Italy has also witnessed the growing custom of including green elements in tall buildings, in the envelopes, at the bases, sides or interiors. The use of vegetation not only concerns new constructions, but also the redevelopment of existing towers, sometimes offering a chance even to buildings that originally lack significant value. Greenery applied to Italian skyscrapers, however, should raise questions about the actual environmental, economic and social sustainability of these design solutions, which sometimes seem to respond to mere aesthetic and ornamental requirements or marketing demands. Through the analysis of certain Italian skyscrapers characterized by the presence of greenery, this study aims to underline the potential and the importance of the use of vegetation in the tall building, an architectural type historically in contrast with natural elements, triggering a reflection on intervention criteria susceptible of application also at wider and more differentiated scales.

Abstract Local adaptation of animals to the environment can abruptly become a burden when faced with rapid climatic changes such as those foreseen for the Italian peninsula over the next 70 years. Our study investigates the genetic structure of the Italian goat populations and links it with the environment and how genetics might evolve over the next 50 years. We used one of the largest national datasets including > 1000 goats from 33 populations across the Italian peninsula collected by the Italian Goat Consortium and genotyped with over 50 k markers. Our results showed that Italian goats can be discriminated in three groups reflective of the Italian geography and its geo-political situation preceding the country unification around two centuries ago. We leveraged the remarkable genetic and geographical diversity of the Italian goat populations and performed landscape genomics analysis to disentangle the relationship between genotype and environment, finding 64 SNPs intercepting genomic regions linked to growth, circadian rhythm, fertility, and inflammatory response. Lastly, we calculated the hypothetical future genotypic frequencies of the most relevant SNPs identified through landscape genomics to evaluate their long-term effect on the genetic structure of the Italian goat populations. Our results provide an insight into the past and the future of the Italian local goat populations, helping the institutions in defining new conservation strategy plans that could preserve their diversity and their link to local realities challenged by climate change.

Cirneco dell’Etna is an old Italian breed of scent hunting dogs. Commonly used genomic measures such as heterozygosity, fixation indexes, and runs of homozygosity can help to improve knowledge about its genetic diversity. This study aimed to: (i) investigate Cirneco’s genomic background, (ii) quantify its genomic inbreeding, and (iii) detect genomic regions differentiating the Cirneco’s two allowed coat colours, self-coloured fawn and tan and white. Canine 230 K SNP BeadChips was used to investigate 24 Cirneco (19 self-coloured fawn, and 5 tan and white) and other 106 dogs from eight phylogenetically and historically related breeds. The genetic distance, ancestry, and relationship among breeds were explored by multidimensional scaling, Reynolds distances, phylogenetic tree, and admixture analysis. The genomic inbreeding (FROH) was calculated for each breed. Averaged Wright’s fixation index ST was used to identify the genes that most differentiated the two groups of Cirneco. All analyses highlighted that Segugio Italiano and Kelb tal Fenek are the closest breeds to Cirneco. Within the breed, tan and white subjects showed a more heterogeneous genetic background and a lower inbreeding in comparison with self-coloured fawn ones, even though more than half of the latter presented a superimposable admixture. The gene that most differentiated these two groups is Microphthalmia-Associated Transcription Factor (MITF), previously associated with white spotting in other breeds. Given the small size of the Cirneco population and its open registry, its management should carefully combine morphological and genealogical evaluations with genetic tools to identify the best breeders while maintaining an acceptable genetic pool.Highlights The genomic analysis demonstrated that Segugio Italiano and Kelb tal Fenek are genetically related to the Cirneco. The MITF gene is responsible for white blazing in Cirneco as in many other dog breeds. Genomic tools should be integrated with phenotypic and genealogic evaluations in the management of Italian autochthonous dog breeds to safeguard their welfare and biodiversity.

East Coast fever, a tick-borne cattle disease caused by the Theileria parva parasite, is among the biggest natural killers of cattle in East Africa, leading to over 1 million deaths annually. Here we report on the genetic analysis of a cohort of Bos indicus (Boran) cattle demonstrating heritable tolerance to infection with T. parva (h2 = 0.65, s.e. 0.57). Through a linkage analysis we identify a 6 Mb genomic region on bovine chromosome 15 that is significantly associated with survival outcome following T. parva exposure. Testing this locus in an independent cohort of animals replicates this association with survival following T. parva infection. A stop gained variant in a paralogue of the FAF1 gene in this region was found to be highly associated with survival across both related and unrelated animals, with only one of the 20 homozygote carriers (T/T) of this change succumbing to the disease in contrast to 44 out of 97 animals homozygote for the reference allele (C/C). Consequently, we present a genetic locus linked to tolerance of one of Africa’s most important cattle diseases, raising the promise of marker-assisted selection for cattle that are less susceptible to infection by T. parva. Author summary More than a million cattle die of East Coast fever in Africa each year, the impact of which disproportionately falls onto low-income, smallholder farmers. The lack of a widely accessible vaccine, heavy reliance on chemicals to control the tick vector and inadequate drug treatments means that new approaches for controlling the disease are urgently required. Through a genetic study of an extended pedigree of Boran cattle that are more than three times less likely to succumb to the disease than matched controls, we identify a region on chromosome 15 of the cattle genome associated with a high level of tolerance to the disease. We show that a nonsense variant in a predicted paralogue of FAS-associated factor 1 (FAF1) in this region is also associated with survival in an independent cohort, and is linked to rates of cell expansion during infection. This genetic variant can therefore support marker-assisted selection, allowing farmers to breed tolerant cattle and offers a route to introduce this beneficial DNA to non-native breeds, enabling reduced disease incidence and increased productivity, which would be of benefit to millions of rural smallholder farmers across Africa.

The comparative genomics of domesticated lineages can yield insights into the signatures of artificial selection. This study sequences 79 water buffalo genomes from 7 breeds and reveals examples of convergent domestication at the genetic level between water buffalo and cattle.

Background: There is limited research on brain lesions in children with cerebral visual impairment (CVI) of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value.Aim: This study aimed to investigate overall patterns of brain lesions and associations with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI.Methods: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions (right hemisphere, left hemisphere, visual pathways) and summed for total scores. Non-parametric analyses were conducted.Results: 28 children had clinical brain MRI scans available [44% of total sample, Group A (lower severity of visual dysfunctions) n = 16, Group B (higher severity) n = 12]. Total brain scores ranged between 0 and 18 (Group A mdn = 7, IQR = 0.8–10.0, Group B mdn = 10, IQR = 6.5–11.8) and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables (acuity, contrast sensitivity).Conclusion: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments.