A combined genome-wide approach identifies a new potential candidate marker associated with the coat color sidedness in cattle

Coat color is one of the most important phenotypic features in livestock breeds. Cinisara is a local cattle breed generally of uniform black color which occasionally presents a particular phenotype, with animals typically display a white band along their spine, from the head to the tail, and on the ventral line (color sidedness). Therefore, this breed provides an ideal model to study the genetic components underlying phenotypic variation in coat color. A total of 63 animals, ten with sidedness phenotype and 53 with uniform black color were genotyped with Illumina Bovine 50 K. The comparison among genome-wide association study and FST analysis revealed a single nucleotide polymorphism (SNP), ARS-BFGL-NGS-55928, significantly associated with the trait. Only one gene (PLK2)was annotated near the associated SNP in a window of ±200 kb. The protein encoded by this gene is a member of the polo-like kinases, the same family of several known coat-color candidate genes. Based on the reported results, we draw the possible conclusion that the identified marker is potentially associated with the coat color sidedness in Cinisara. The local breeds with their genetic variability represent an important resource and model to study the genetic basis affecting peculiar traits. Future studies would be particularly relevant to refine these results and to better understand the genetic basis for this phenotype

Clinical and Pathophysiological Insights Into Immunological Mediated Glomerular Diseases in Childhood

The kidney is often the target of immune system dysregulation in the context of primary or systemic disease. In particular, the glomerulus represents the anatomical entity most frequently involved, generally as the expression of inflammatory cell invasion or circulant or in situ immune-complex deposition. Glomerulonephritis is the most common clinical and pathological manifestation of this involvement. There are no universally accepted classifications for glomerulonephritis. However, recent advances in our understanding of the pathophysiological mechanisms suggest the assessment of immunological features, biomarkers, and genetic analysis. At the same time, more accurate and targeted therapies have been developed. Data on pediatric glomerulonephritis are scarce and often derived from adult studies. In this review, we update the current understanding of the etiologic events and genetic factors involved in the pathogenesis of pediatric immunologically mediated primitive forms of glomerulonephritis, together with the clinical spectrum and prognosis. Possible new therapeutic targets are also briefly discussed

Structural bases of the altered catalytic properties of a pathogenic variant of apoptosis inducing factor

The apoptosis-inducing factor (AIF) is a FAD-containing protein playing critical roles in caspase-independent apoptosis and mitochondrial respiratory chain biogenesis and maintenance. While its lethal role is well known, the details of its mitochondrial function remain elusive. So far, nineteen allelic variants of AIF have been associated to human diseases, mainly affecting the nervous system. A strict correlation is emerging between the degree of impairment of its ability to stabilize the charge-transfer (CT) complex between FAD and NAD+ and the severity of the resulting pathology. Recently, we demonstrated that the G307E replacement in murine AIF (equivalent to the pathogenic G308E in the human protein) dramatically decreases the rate of CT complex formation through the destabilization of the flavoprotein interaction with NAD(H). To provide further insights into the structural bases of its altered functional properties, here we report the first crystal structure of an AIF pathogenic mutant variant in complex with NAD+ (murine AIF-G307ECT) in comparison with its oxidized form. With respect to wild type AIF, the mutation leads to an altered positioning of NAD+ adenylate moiety, which slows down CT complex formation. Moreover, the altered balance between the binding of the adenine/nicotinamide portions of the coenzyme determines a large drop in AIF-G307E ability to discriminate between NADH and NADPH

Micromixing and microchannel design: Vortex shape and entropy

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In very recent years microdevices, due to their potency in replacing large-scale conventional laboratory instrumentation, are becoming a fast and low cost technology for the treatment of several chemical and biological processes. In particular microfluidics has been massively investigated, aiming at improving the performance of chemical reactors. This is because of the fact that reaction is often an interface phenomenon where the greater the surface to volume ratio, the higher the reaction speed, and microscale mixing increases the interfacial area (in terms of mixing-induced-by-vortices generation). However, microfluidic systems suffer from the limitation that they are characterized mostly by very low Reynolds numbers, with the consequence that (i) they cannot take advantage from the turbulence mixing support, and (ii) viscosity hampers proper vortex detection. Therefore, the proper design of micro-channels (MCs) becomes essential. In this framework, several geometries have been proposed to induce mixing vortices in MCs. However a quantitative comparison between proposed geometries in terms of their passive mixing potency can be done only after proper definition of vortex formation (topology, size) and mixing performance. The objective of this study is to test the ability of different fluid dynamic metrics in vortex detection and mixing effectiveness in micromixers. This is done numerically solving different conditions for the flow in a classic passive mixer, a ring shaped MC. We speculate that MCs design could take advantage from fluidic metrics able to rank properly flow related mixing

Genome-wide scan for Runs of Homozygosity in Valle del Belice sheep

The current availability of very large numbers of single nucleotide polymorphisms (SNPs) throughout the genome makes these markers particularly suitable for the detection of genomic regions where a reduction in heterozygosity occurred and offers new opportunities to improve the accuracy of inbreeding (F) estimates. Runs of homozygosity (ROH) are contiguous lengths of homozygous segments of the genome where the two haplotypes inherited from the parents are identical. Here, we investigated the occurrence and the distribution of ROH in medium-density SNP genotypes (~ 50 000) in order to characterize autozygosity in 512 individuals of Valle del Belice sheep and identify the regions of the genome with high ROH frequencies. A total of 11 629 ROH were identified. All individuals displayed at least one ROH > 1 Mb. The mean value of FROH>1Mb was 0.084\ub10.061. ROH that were shorter than 10 Mb predominated. The highest coverage of chromosome (OAR) by ROH was observed on OAR24, whereas the lowest one was observed on OAR1. A typical pattern was observed for the number of ROH per OAR with higher values in the first three chromosomes. There was a considerable difference among animals for the number of ROH segments and the length of the genome covered by ROH. The genomic regions most commonly associated with ROH were identified by selecting the top 1% of the SNPs most commonly observed in ROH within breed. A total of 239 SNPs were considered as candidate SNPs and we identified 107 potential candidate genes that may be under directional selection. Six genomic regions located on six chromosomes (OAR2, OAR3, OAR4, OAR10, OAR11 and OAR23), corresponding to ROH island, presented hotspot of autozygosity. According to KEGG database, a majority of the genes were involved in multiple signaling and signal transduction pathways in a wide variety of cellular and biochemical processes. The ROH islands spanned several candidate genes which influence traits that are associated with adaptability and with the regulation of immune responses (NPAS2, PDCL3, SERPINF1 and SERPINF2) and we did not identified candidate genes with important influence on milk production traits in sheep. The Valle del Belice breed is subjected to limited breeding selection programs for milk production traits, but shows excellent adaptability to the local environments. Therefore, these results suggest at least a partial role of natural selection in shaping the genome of Valle del Belice sheep breed

Genome wide Copy Number Variation (CNV) detection in Cinisara cattle breed

Copy Number Variations (CNVs) are classes of polymorphic genomic regions including deletions, duplications and insertions of DNA fragments from at least 0.5 kb up to several Mb. CNV represents an important source of genetic variability that provides genomics structural information complementary to the single nucleotide polymorphism (SNP) data. Some CNVs have been shown to be important in both normal phenotypic variability and disease susceptibility in livestock. Several approaches to identify CNVs including FISH, aCGH, SNP array or NGS, were proposed and among these SNP genotyping is relatively low cost, high-throughput and high coverage method. The aim of this study was to identify the CNVs in 71 animals of Cinisara breed using Illumina BovineSNP50 BeadChip v2. PennCNV software, which incorporates Log R ratio and B allele frequency at each SNP marker, was used to identify CNVs. Seven animals showed not shared CNVs, as well as autosomes 19, 21, 22. Chromosome 25 presented no CNVs at all. A final number of 322 CNVs were detected. The average number of CNVs was 4.5 per individual, with an average length and median size of 143.04 kb and 122.14 kb, respectively. All CNVs were grouped in CNV regions (CNVRs) and a total of 107 CNVRs, ranged from 50 to ~500 kb, were detected, which covered 4.90 Mb of polymorphic sequence and corresponded to 0.18% of the total genome length. In particular, we found 81 CNVRs with only gain (duplication), 22 with only loss (deletion), and four CNVRs with both. Furthermore, 8 CNVRs with >1%, 77 with >2.5%, and 22 with >5% frequency, were found. CNVRs having the highest frequency were located on Chr3:120501439-120647330 and Chr23:34673581-35007295, whereas the greatest number of genes was mapped in only one CNVR located on Chr 17:74123863-74393620. A total of 241 genes were included in the identified CNVRs. According to KEGG and DAVID database, most of the genes were involved in multiple signaling and signal transduction pathways in a wide variety of cellular and biochemical processes, such as immune response, adaptability, and olfactory receptors pathway. Further studies, using different algorithms and validating the CNVs discovered, will be conducted to corroborate these preliminary results on the CNVRs detected. These results will be used for the investigation of genomic changes and features of interest in the Cinisara breed, such as for association with functional or production traits and for biodiversity studies

High resolution simulations of a flash flood near Venice.

Abstract. During the MAP D-PHASE (Mesoscale Alpine Programme, Demonstration of Probabilistic Hydrological and Atmospheric Simulation of flood Events in the Alpine region) Operational Period (DOP, 1 June–30 November 2007) the most intense precipitation event observed south of the Alps occurred over the Venice Lagoon. In the early morning of 26 September 2007, a mesoscale convective system formed in an area of convergence between a south-easterly low level jet flowing along the Adriatic Sea and a north-easterly barrier-type wind south of the Alps, and was responsible for precipitation exceeding 320 mm in less than 12 h, 240 mm of which in only 3 h. The forecast rainfall fields, provided by several convection resolving models operated daily for the D-PHASE project, have been compared. An analysis of different aspects of the event, such as the relevant mechanisms leading to the flood, the main characteristics of the MCS, and an estimation of the predictability of the episode, has been performed using a number of high resolution, convection resolving models (MOLOCH, WRF and MM5). Strong sensitivity to initial and boundary conditions and to model parameterization schemes has been found. Although low predictability is expected due to the convective nature of rainfall, the forecasts made more than 24 h in advance indicate that the larger scale environment driving the dynamics of this event played an important role in favouring the achievement of a relatively good accuracy in the precipitation forecasts

Genomic structural diversity in local goats: Analysis of copy-number variations

Copy-number variations (CNVs) are one of the widely dispersed forms of structural variations in mammalian genomes, and are present as deletions, insertions, or duplications. Only few studies have been conducted in goats on CNVs derived from SNP array data, and many local breeds still remain uncharacterized, e.g., the Sicilian goat dairy breeds. In this study, CNV detection was performed, starting from the genotypic data of 120 individuals, belonging to four local breeds (Argentata dell’Etna, Derivata di Siria, Girgentana, and Messinese), genotyped with the Illumina GoatSNP50 BeadChip array. Overall, 702 CNVs were identified in 107 individuals using PennCNV software based on the hidden Markov model algorithm. These were merged in 75 CNV regions (CNVRs), i.e., regions containing CNVs overlapped by at least 1 base pair, while 85 CNVs remained unique. The part of the genome covered by CNV events was 35.21 Mb (1.2% of the goat genome length). Functional annotation of the CNVRs allowed the identification of 139 genes/loci within the most frequent CNVRs that are involved in local adaptations, such as coat colour (ADAMTS20 and EDNRA), mild behaviour (NR3C2), immune response (EXOC3L4 and TNFAIP2), reproduction (GBP1 and GBP6), and olfactory receptors (OR7E24). This study provides insights into the genomic variations for these Sicilian dairy goat breeds and should be of value for future studies to identify the relationships between this type of genetic variation and phenotypic traits

Genome-Wide Association Study Identifies New Candidate Markers for Somatic Cells Score in a Local Dairy Sheep

In the Mediterranean basin countries, the dairy sheep production is usually based on local breeds, which are very well-adapted to their production systems and environments and can indeed guarantee income, employment, and economic viability in areas where production alternatives are scarce or non-existent. Mastitis is still one of the greatest problems affecting commercial milk production. However, genetic evaluation of mastitis is particularly difficult because of its low heritability and the categorical nature of the trait. The aim of this study was to identify genomic regions putatively associated with somatic cells count (SCC) in the local economically important Valle del Belice sheep breed using of deregressed breeding values (DEBV) as response variables. All the samples were genotyped using the Illumina OvineSNP50K BeadChip. Genome-wide association analysis was carried out based on regression of DEBV. A total of eight markers were found to be significantly associated with log-transformed SCC. Several candidate genes associated with SCC were identified related to immunity system and udder conformation. The results can help improving the competitiveness of the local Valle del Belìce breed. Further studies considering a higher sample size or independent population will be needed to confirm our results

Genomic diversity and population structure analysis reveal few genetic differences among Ethiopian indigenous sheep populations

African sheep, like other domestic sheep, are domesticated from the Asiatic mouflon (Ovis orientalis). They entered the continent through the North and the Horn of Africa regions following maritime and terrestrial trading routes. Ethiopia is one of the main entry points of various plant and animal domesticates into Africa. It is characterised by diverse agro-ecologies, ancient human ethnic diversity and the presence of indigenous sheep breeds/populations of unprecedented morphological diversity (e.g. tail types). Here, we investigate the genome diversity and population structure of 146 unrelated animals from 11 Ethiopian indigenous sheep populations. DNA was extracted from ear tissue punches and genotyped with the Illumina Ovine 50K SNP BeadChip assay. Sheep populations from The Caribbean, Europe, Middle East and China as well as from western, northern and southern Africa were included to clarify the genetic history of origin, introduction and dispersal of the species into Ethiopia. Principal component analysis (PCA), clearly separated all Ethiopian sheep from the other populations. Population structure and phylogenetic (neighbour-joining tree) analysis subdivided the Ethiopian indigenous sheep into three genetic clusters corresponding to their tail morphology (rump fat-tailed, short fat-tailed and long fat/thin-tailed population). It supports a common genetic ancestry for populations of each tail type in the country. Genetic distances among the Ethiopian populations were positively correlated with geographic distances (Mantel test, P < 0.001, r = 0.465) and the highest genetic diversity was recorded in the fat-tailed (short, rump and/or long fat-tailed) close to the Bab-el-Mandeb strait. However, despite their distinct morphology and separate geographic distribution, little genetic differentiation between Ethiopian populations are observed. This is most likely a consequence of their ancient and modern intermixing following their introduction into the country