Genome-wide analyses reveal population structure and identify candidate genes associated with tail fatness in local sheep from a semi-arid area.

Under a climate change perspective, the genetic make-up of local livestock breeds showing adaptive traits should be explored and preserved as a priority. We used genotype data from the ovine 50 k Illumina BeadChip for assessing breed autozygosity based on runs of homozygosity (ROH) and fine-scale genetic structure and for detecting genomic regions under selection in 63 Tunisian sheep samples. The average genomic inbreeding coefficients based on ROH were estimated at 0.017, 0.021, and 0.024 for Barbarine (BAR, n = 26), Noire de Thibar (NDT, n = 23), and Queue fine de l'Ouest (QFO, n = 14) breeds, respectively. The genomic relationships among individuals based on identity by state (IBS) distance matrix highlighted a recent introgression of QFO into the BAR and a genetic differentiation of NDT samples, possibly explained by past introgression of European gene pools. Genome-wide scan for ROH across breeds and within the BAR sample set identified an outstanding signal on chromosome 13 (46.58-49.61 Mbp). These results were confirmed using FST index, differentiating fat vs. thin-tailed individuals. Candidate genes under selection pressure (CDS2, PROKR1, and BMP2) were associated to lipid storage and probably preferentially selected in fat-tailed BAR animals. Our findings suggest paying more attention to preserve the genetic integrity and adaptive alleles of local sheep breeds.

Genome-wide analysis reveals the patterns of genetic diversity and population structure of 8 Italian local chicken breeds.

The aim of this study was to conduct a genome-wide comparative analysis of 8 local Italian chicken breeds (Ermellinata di Rovigo, Millefiori di Lonigo [PML], Polverara Bianca, Polverara Nera, Padovana, Pepoi [PPP], Robusta Lionata, and Robusta Maculata), all under a conservation plan, to understand their genetic diversity and population structure. A total of 152 animals were analyzed using the Affymetrix Axiom 600 K Chicken Genotyping Array. The levels of genetic diversity were highest and lowest in PML and PPP, respectively. The results of genomic inbreeding based on runs of homozygosity (ROH; FROH) showed marked differences among breeds and ranged from 0.161 (PML) to 0.478 (PPP). Furthermore, in all breeds, short ROH (<4 Mb in length) were more frequent than long segments. Patterns of genetic differentiation, model-based clustering, and neighbor networks showed that most breeds formed nonoverlapping clusters and were clearly separate populations. The 2 Polverara breeds shared a similar genetic background and showed the lowest genetic differentiation in comparison with purebred lines; the local populations showed separated groups. PPP and PML were closer to the group of the purebred broiler lines (BRSA, BRSB, BRDA, and BRDB). Six genomic regions are presented as hotspots of autozygosity among the Italian chicken breeds, with candidate genes involved in multiple morphological phenotypes as breast muscle, muscle dry matter content, and body weight. This study is the first exhaustive genome-wide analysis of the diversity of these Italian local chickens from Veneto region. We conclude that breeds have conserved authentic genetic patterns. The results are of significant importance because they will help design and implement conservation strategies. In fact, the conservation of these breeds may also have positive impacts on the local economy, niche traditional markets, and offering a source of high-quality products to consumers. In this context, genomic information may play a crucial role in the management of local breeds.

Genome-wide assessment of diversity and differentiation between original and modern Brown cattle populations.

Identifying genomic regions involved in the differences between breeds can provide information on genes that are under the influence of both artificial and natural selection. The aim of this study was to assess the genetic diversity and differentiation among four different Brown cattle populations (two original vs. two modern populations) and to characterize the distribution of runs of homozygosity (ROH) islands using the Illumina Bovine SNP50 BeadChip genotyping data. After quality control, 34 735 SNPs and 106 animals were retained for the analyses. Larger heterogeneity was highlighted for the original populations. Patterns of genetic differentiation, multidimensional scaling, and the neighboring joining tree distinguished the modern from the original populations. The FST -outlier identified several genes putatively involved in the genetic differentiation between the two groups, such as stature and growth, behavior, and adaptability to local environments. The ROH islands within both the original and the modern populations overlapped with QTL associated with relevant traits. In modern Brown (Brown Swiss and Italian Brown), ROH islands harbored candidate genes associated with milk production traits, in evident agreement with the artificial selection conducted to improve this trait in these populations. In original Brown (Original Braunvieh and Braunvieh), we identified candidate genes related with fat deposition, confirming that breeding strategies for the original Brown populations aimed to produce dual-purpose animals. Our study highlighted the presence of several genomic regions that vary between Brown populations, in line with their different breeding histories.

Comparative selection signature analyses identify genomic footprints in Reggiana cattle, the traditional breed of the Parmigiano-Reggiano cheese production system.

Reggiana is an autochthonous cattle breed reared mainly in the province of Reggio Emilia, located in the North of Italy. Reggiana cattle (originally a triple-purpose population largely diffused in the North of Italy) are characterised by a typical solid red coat colour. About 2500 cows of this breed are currently registered to its herd book. Reggiana is now considered a dual-purpose breed even if it is almost completely dedicated to the production of a mono-breed branded Protected Designation of Origin Parmigiano-Reggiano cheese, which is the main driver of the sustainable conservation of this local genetic resource. In this study, we provided the first overview of genomic footprints that characterise Reggiana and define the diversity of this local cattle breed. A total of 168 Reggiana sires (all bulls born over 35 years for which semen was available) and other 3321 sires from 3 cosmopolitan breeds (Brown, Holstein and Simmental) were genotyped with the Illumina BovineSNP50 panel. ADMIXTURE analysis suggested that Reggiana breed might have been influenced, at least in part, by the other three breeds included in this study. Selection signatures in the Reggiana genome were identified using three statistical approaches based on allele frequency differences among populations or on properties of haplotypes segregating in the populations (fixation index (FST); integrated haplotype score; cross-population extended haplotype homozygosity). We identified several regions under peculiar selection in the Reggiana breed, particularly on bovine chromosome (BTA) 6 in the KIT gene region, that is known to be involved in coat colour pattern distribution, and within the region of the LAP3, NCAPG and LCORL genes, that are associated with stature, conformation and carcass traits. Another already known region that includes the PLAG1 gene (BTA14), associated with conformation traits, showed a selection signature in the Reggiana cattle. On BTA18, a signal of selection included the MC1R gene that causes the red coat colour in cattle. Other selection sweeps were in regions, with high density of quantitative trait loci for milk production traits (on BTA20) and in several other large regions that might have contributed to shape and define the Reggiana genome (on BTA17 and BTA29). All these results, overall, indicate that the Reggiana genome might still contain several signs of its multipurpose and non-specialised utilisation, as already described for other local cattle populations, in addition to footprints derived by its ancestral origin and by its adaptation to the specialised Parmigiano-Reggiano cheese production system.

Genome-wide analyses reveal the regions involved in the phenotypic diversity in Sicilian pigs.

Nero Siciliano (Sicilian Black, SB) is a local pig breed generally of uniform black color. In addition to this officially recognized breed, there are animals showing morphological characteristics resembling the SB but with gray hair (Sicilian Grey, SG). The SG, compared with the SB, also shows a more compact structure with greater transverse diameters, higher average daily gains and lower thickness of the back fat. In this study, using the Illumina PorcineSNP60 BeadChip, we run genome-wide analyses to identify regions that may explain the phenotypic differences between SB (n = 21) and SG (n = 27) individuals. Combining the results of the two case-control approaches (GWAS and FST ), we identified two significant regions, one on SSC5 (95 401 083 bp) and one on SSC15 (55 051 435 bp), which contains several candidate genes related to growth traits in pig. The results of the Bayesian population differentiation approach identified a marker near the MGAT4C, a gene associated with average daily gain in pigs. Finally, scanning the genome for runs of homozygosity islands, we found that the two groups have different runs of homozygosity islands, with several candidate genes involved in coat color (in SG) or related to different pig performance traits (in SB). In summary, the two analyzed groups differed for several phenotypic traits, and genes involved in these traits (growth, meat traits and coat color) were detected. This study provided another contribution to the identification of genomic regions involved in phenotypic variability in local pig populations.

Serum biomarkers for sepsis in children with febrile neutropenia and cancer.

The National Institute for Health and Care Excellence (NICE) defines febrile neutropenia or "neutropenic sepsis" as a patient with an absolute neutrophil count (ANC) less than 0.5 x 109/L and temperature >38°C or signs and symptoms of sepsis.

Genome-wide association studies for milk production traits in Valle del Belice sheep using repeated measures.

Genome-wide association studies (GWASes) have become a powerful tool for identifying genomic regions associated with important traits in livestock. Milk production traits in dairy sheep are measured at different time points during their life span. Using phenotypic data generated from longitudinal traits could improve the power of association studies but until now have received less attention in GWASes as a methodology and has not been implemented. The aim of this study was to carry out a GWAS for milk production traits in Valle del Belice sheep using repeated measures. After quality control, 469 ewes and 37 228 SNPs were retained for the analysis, and phenotypic data included 5586 test-day records for five milk production traits (milk yield, MY; fat yield and percentage, FY and F%; protein yield and percentage, PY and P%). Nine SNPs located within or close to known genes were found to be associated with milk production traits. In particular, rs398340969, associated with both milk yield and protein yield, is located within the DCPS gene. In addition, rs425417915 and rs417079368, both associated with both fat percentage and protein percentage, are located within the TTC7B gene and at 0.37 Mb within the SUCNR1 gene respectively. In summary, the use of repeated records was beneficial for mapping genomic regions affecting milk production traits in the Valle del Belice sheep.

Impact of malnutrition on survival and infections among pediatric patients with cancer: a retrospective study.

OBJECTIVE: Recognizing and managing malnutrition among hospitalized children affected by cancer is a rising need. Awareness and consideration of malnutrition among clinicians are still largely insufficient. This can principally be explained by the lack of consciousness and the shortage of easy and objective tools to identify malnutrition status. The aim of this study is to explore the impact of malnutrition on survival and infections among a population of pediatric patients with cancer. PATIENTS AND METHODS: All children aged between 3 and 18 years, newly diagnosed with a malignancy between August 2013 and April 2018, were included in our study. We assessed nutritional risk at diagnosis (with STRONGkids), then we evaluated anthropometric measurements (BMI Z-scores and weight loss), data about survival and number of hospitalization for febrile neutropenia (FN) in the first year after diagnosis. Cut-off values for malnourishment were chosen as BMI Z-score ≤-2.0. RESULTS: One hundred twenty-six pediatric cancer patients were included in the study. At diagnosis 36 pediatric cancer patients (28.6%) were at high risk of malnutrition (STRONGkids 4 or 5), whereas 6 (4.7%) others were malnourished (BMI Z-score≤-2.0). The risk of mortality and the rate of infections (≥3 hospitalizations for FN episodes) were significantly increased by malnutrition and rapid weight loss in the initial phase of treatment (3-6 months after diagnosis). Multivariate analysis confirmed the independent effect of weight loss≥ 5% at 3 months on both survival and infections, and the independent impact of a high risk of malnutrition at diagnosis on infections. CONCLUSIONS: A personalized evaluation of nutritional risk at diagnosis and a close monitoring of nutritional status during the initial phase of treatment are crucial for ensuring a timely and personalized nutritional intervention, which may potentially improve tolerance to chemotherapy and survival, and prevent prolonged hospitalization for infections in childhood cancer patients.

Genome-wide association study reveals the locus responsible for microtia in Valle del Belice sheep breed.

Microtia is a congenital deformity of the outer ear with phenotypes varying from a small auricle to total absence (anotia). The genetic basis is still poorly understood, and very few studies have been performed in sheep. Valle del Belice sheep is a breed showing microtia. The aim of this study was to identify the potential genomic regions involved in microtia in sheep. A total of 40 individuals, 20 with microtia and 20 normal, were genotyped with the Illumina OvineSNP50 BeadChip. The comparison among the results from a genome-wide association study, Fisher's exact test and FST analysis revealed a single strong association signal: rs419889303 on chromosome 1, located within intron 3 of the CLRN1 gene. Our study suggests for the first time that this novel candidate gene is responsible for microtia in sheep. Additional analysis based on the sequencing would help confirm our findings and allow for the proposal of a precise genetic basis for microtia in sheep.

Genome-wide identification of runs of homozygosity islands and associated genes in local dairy cattle breeds.

Runs of homozygosity (ROH) are widely used as predictors of whole-genome inbreeding levels in cattle. They identify regions that have an unfavorable effect on a phenotype when homozygous, but also identify the genes associated with traits of economic interest present in these regions. Here, the distribution of ROH islands and enriched genes within these regions in four dairy cattle breeds were investigated. Cinisara (71), Modicana (72), Reggiana (168) and Italian Holstein (96) individuals were genotyped using the 50K v2 Illumina BeadChip. The genomic regions most commonly associated with ROHs were identified by selecting the top 1% of the single nucleotide polymorphisms (SNPs) most commonly observed in the ROH of each breed. In total, 11 genomic regions were identified in Cinisara and Italian Holstein, and eight in Modicana and Reggiana, indicating an increased ROH frequency level. Generally, ROH islands differed between breeds. The most homozygous region (>45% of individuals with ROH) was found in Modicana on chromosome 6 within a quantitative trail locus affecting milk fat and protein concentrations. We identified between 126 and 347 genes within ROH islands, which are involved in multiple signaling and signal transduction pathways in a wide variety of biological processes. The gene ontology enrichment provided information on possible molecular functions, biological processes and cellular components under selection related to milk production, reproduction, immune response and resistance/susceptibility to infection and diseases. Thus, scanning the genome for ROH could be an alternative strategy to detect genomic regions and genes related to important economic traits.

Runs of homozygosity reveal genome-wide autozygosity in Italian sheep breeds.

The availability of dense single nucleotide polymorphism (SNP) assays allows for the determination of autozygous segments based on runs of consecutive homozygous genotypes (ROH). The aim of the present study was to investigate the occurrence and distribution of ROH in 21 Italian sheep breeds using medium-density SNP genotypes in order to characterize autozygosity and identify genomic regions that frequently appeared in ROH within individuals, namely ROH islands. After filtering, the final number of animals and SNPs retained for analyses were 502 and 46 277 respectively. A total of 12 302 ROH were identified. The mean number of ROH per breed ranged from 10.58 (Comisana) to 44.54 (Valle del Belice). The average length of ROH across breeds was 4.55 Mb and ranged from 3.85 Mb (Biellese) to 5.51 Mb (Leccese). Valle del Belice showed the highest value of inbreeding on the basis of ROH (FROH  = 0.099), whereas Comisana showed the lowest (FROH  = 0.016), and high standard deviation values revealed high variability in autozygosity levels within each breed. Differences also existed in the length of ROH. Analysis of the distribution of ROH according to their size showed that, for all breeds, the majority of the detected ROH were <10 Mb in length, with a few long ROH >25 Mb. The levels of ROH that we estimated here reflect the inbreeding history of the investigated sheep breeds. These results also highlight that ancient and recent inbreeding have had an impact on the genome of the Italian sheep breeds and suggest that several animals have experienced recent autozygosity events. Comisana and Bergamasca appeared as the less consanguineous breeds, whereas Barbaresca, Leccese and Valle del Belice showed ROH patterns typically produced by recent inbreeding. Moreover, within the genomic regions most commonly associated with ROH, several candidate genes were detected.

Preselection statistics and Random Forest classification identify population informative single nucleotide polymorphisms in cosmopolitan and autochthonous cattle breeds.

Commercial single nucleotide polymorphism (SNP) arrays have been recently developed for several species and can be used to identify informative markers to differentiate breeds or populations for several downstream applications. To identify the most discriminating genetic markers among thousands of genotyped SNPs, a few statistical approaches have been proposed. In this work, we compared several methods of SNPs preselection (Delta, F st and principal component analyses (PCA)) in addition to Random Forest classifications to analyse SNP data from six dairy cattle breeds, including cosmopolitan (Holstein, Brown and Simmental) and autochthonous Italian breeds raised in two different regions and subjected to limited or no breeding programmes (Cinisara, Modicana, raised only in Sicily and Reggiana, raised only in Emilia Romagna). From these classifications, two panels of 96 and 48 SNPs that contain the most discriminant SNPs were created for each preselection method. These panels were evaluated in terms of the ability to discriminate as a whole and breed-by-breed, as well as linkage disequilibrium within each panel. The obtained results showed that for the 48-SNP panel, the error rate increased mainly for autochthonous breeds, probably as a consequence of their admixed origin lower selection pressure and by ascertaining bias in the construction of the SNP chip. The 96-SNP panels were generally more able to discriminate all breeds. The panel derived by PCA-chrom (obtained by a preselection chromosome by chromosome) could identify informative SNPs that were particularly useful for the assignment of minor breeds that reached the lowest value of Out Of Bag error even in the Cinisara, whose value was quite high in all other panels. Moreover, this panel contained also the lowest number of SNPs in linkage disequilibrium. Several selected SNPs are located nearby genes affecting breed-specific phenotypic traits (coat colour and stature) or associated with production traits. In general, our results demonstrated the usefulness of Random Forest in combination to other reduction techniques to identify population informative SNPs.

Penalized classification for optimal statistical selection of markers from high-throughput genotyping: application in sheep breeds.

The identification of individuals' breed of origin has several practical applications in livestock and is useful in different biological contexts such as conservation genetics, breeding and authentication of animal products. In this paper, penalized multinomial regression was applied to identify the minimum number of single nucleotide polymorphisms (SNPs) from high-throughput genotyping data for individual assignment to dairy sheep breeds reared in Sicily. The combined use of penalized multinomial regression and stability selection reduced the number of SNPs required to 48. A final validation step on an independent population was carried out obtaining 100% correctly classified individuals. The results using independent analysis, such as admixture, F st, principal component analysis and random forest, confirmed the ability of these methods in selecting distinctive markers. The identified SNPs may constitute a starting point for the development of a SNP based identification test as a tool for breed assignment and traceability of animal products.

Genome-wide analysis in endangered populations: a case study in Barbaresca sheep.

Analysis of genomic data is becoming increasingly common in the livestock industry and the findings have been an invaluable resource for effective management of breeding programs in small and endangered populations. In this paper, with the goal of highlighting the potential of genomic analysis for small and endangered populations, genome-wide levels of linkage disequilibrium, measured as the squared correlation coefficient of allele frequencies at a pair of loci, effective population size, runs of homozygosity (ROH) and genetic diversity parameters, were estimated in Barbaresca sheep using Illumina OvineSNP50K array data. Moreover, the breed's genetic structure and its relationship with other breeds were investigated. Levels of pairwise linkage disequilibrium decreased with increasing distance between single nucleotide polymorphisms. An average correlation coefficient <0.25 was found for markers located up to 50 kb apart. Therefore, these results support the need to use denser single nucleotide polymorphism panels for high power association mapping and genomic selection efficiency in future breeding programs. The estimate of past effective population size ranged from 747 animals 250 generations ago to 28 animals five generations ago, whereas the contemporary effective population size was 25 animals. A total of 637 ROH were identified, most of which were short (67%) and ranged from 1 to 10 Mb. The genetic analyses revealed that the Barbaresca breed tended to display lower variability than other Sicilian breeds. Recent inbreeding was evident, according to the ROH analysis. All the investigated parameters showed a comparatively narrow genetic base and indicated an endangered status for Barbaresca. Multidimensional scaling, model-based clustering, measurement of population differentiation, neighbor networks and haplotype sharing distinguished Barbaresca from other breeds, showed a low level of admixture with the other breeds considered in this study, and indicated clear genetic differences compared with other breeds. Attention should be given to the conservation of Barbaresca due to its critical conservation status. In this context, genomic information may have a crucial role in management of small and endangered populations.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

Introduction. SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. Materials and methods. Italian and Spanish metastatic INES patients’ data are reported. SPSS 20.0 was used for statistical analysis. Results. Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. Conclusions. The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data (AU)

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Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

Genomic inbreeding estimation in small populations: evaluation of runs of homozygosity in three local dairy cattle breeds.

In the local breeds with small population size, one of the most important problems is the increase of inbreeding coefficient (F). High levels of inbreeding lead to reduced genetic diversity and inbreeding depression. The availability of high-density single nucleotide polymorphism (SNP) arrays has facilitated the quantification of F by genomic markers in farm animals. Runs of homozygosity (ROH) are contiguous lengths of homozygous genotypes and represent an estimate of the degree of autozygosity at genome-wide level. The current study aims to quantify the genomic F derived from ROH (F ROH) in three local dairy cattle breeds. F ROH values were compared with F estimated from the genomic relationship matrix (F GRM), based on the difference between observed v. expected number of homozygous genotypes (F HOM) and the genomic homozygosity of individual i (F MOL i ). The molecular coancestry coefficient (f MOL ij ) between individuals i and j was also estimated. Individuals of Cinisara (71), Modicana (72) and Reggiana (168) were genotyped with the 50K v2 Illumina BeadChip. Genotypes from 96 animals of Italian Holstein cattle breed were also included in the analysis. We used a definition of ROH as tracts of homozygous genotypes that were >4 Mb. Among breeds, 3661 ROH were identified. Modicana showed the highest mean number of ROH per individual and the highest value of F ROH, whereas Reggiana showed the lowest ones. Differences among breeds existed for the ROH lengths. The individuals of Italian Holstein showed high number of short ROH segments, related to ancient consanguinity. Similar results showed the Reggiana with some extreme animals with segments covering 400 Mb and more of genome. Modicana and Cinisara showed similar results between them with the total length of ROH characterized by the presence of large segments. High correlation was found between F HOM and F ROH ranged from 0.83 in Reggiana to 0.95 in Cinisara and Modicana. The correlations among F ROH and other estimated F coefficients were generally lower ranged from 0.45 (F MOL i -F ROH) in Cinisara to 0.17 (F GRM-F ROH) in Modicana. On the basis of our results, recent inbreeding was observed in local breeds, considering that 16 Mb segments are expected to present inbreeding up to three generations ago. Our results showed the necessity of implementing conservation programs to control the rise of inbreeding and coancestry in the three Italian local dairy cattle breeds.

The genome-wide structure of two economically important indigenous Sicilian cattle breeds.

Genomic technologies, such as high-throughput genotyping based on SNP arrays, provided background information concerning genome structure in domestic animals. The aim of this work was to investigate the genetic structure, the genome-wide estimates of inbreeding, coancestry, effective population size (Ne), and the patterns of linkage disequilibrium (LD) in 2 economically important Sicilian local cattle breeds, Cinisara (CIN) and Modicana (MOD), using the Illumina Bovine SNP50K v2 BeadChip. To understand the genetic relationship and to place both Sicilian breeds in a global context, genotypes from 134 other domesticated bovid breeds were used. Principal component analysis showed that the Sicilian cattle breeds were closer to individuals of Bos taurus taurus from Eurasia and formed nonoverlapping clusters with other breeds. Between the Sicilian cattle breeds, MOD was the most differentiated, whereas the animals belonging to the CIN breed showed a lower value of assignment, the presence of substructure, and genetic links with the MOD breed. The average molecular inbreeding and coancestry coefficients were moderately high, and the current estimates of Ne were low in both breeds. These values indicated a low genetic variability. Considering levels of LD between adjacent markers, the average r(2) in the MOD breed was comparable to those reported for others cattle breeds, whereas CIN showed a lower value. Therefore, these results support the need of more dense SNP arrays for a high-power association mapping and genomic selection efficiency, particularly for the CIN cattle breed. Controlling molecular inbreeding and coancestry would restrict inbreeding depression, the probability of losing beneficial rare alleles, and therefore the risk of extinction. The results generated from this study have important implications for the development of conservation and/or selection breeding programs in these 2 local cattle breeds.

Platinum compounds and sodium metabolism in children with diencephalic glioma.

In this brief report we have described eight children affected by optic pathway/hypothalamus gliomas and treated with carboplatin and/or cisplatin, which developed a derangement of sodium and water metabolism, due to diabetes insipidus (DI) or to syndrome of inappropriate antidiuretic hormone secretion (SIADH) after surgical resection. In four out of these eight patients the treatment with platinum compounds produced prolonged haematological toxicity and in five out of them it caused neurosensorial bilateral hypoacusia. In addition cisplatin worsened electrolytes disturbances. Hence children with DI or SIADH should be carefully monitored before, during and after the treatment with platinum compounds.

Human parvovirus B 19 and Epstein-Barr virus co-infection in a child with hereditary spherocytosis.

BACKGROUND: In patients with chronic congenital haemolytic disorders, human Parvovirus B19 (HPV B19) is frequently involved in pure red-cell aplastic crises. Furthermore, it may inhibit three-lineage haematopoiesis in the bone marrow, causing severe pancytopenia. In such patients, Epstein Barr virus (EBV) infection also seems to share the same mechanism as HPV B19 in inducing bone marrow aplasia, but at present the clinical effect of an infection sustained by both viruses is unknown. CLINICAL REPORT: We present a 7-year-old boy affected by hereditary spherocytosis (HS) who suffered from transient aplastic crisis, in whom laboratory findings revealed a double HPV B19 and EBV infection. CONCLUSIONS: To our knowledge, this is the first report of a case of HPV B19 and EBV co-infection diagnosis in a paediatric patient. Despite underlying HS, no signs of haemolytic anaemia were detected, but the infection only produced transient pancytopenia. Nevertheless, the reason why there was no additive effect of the two viruses on the aplastic crisis is still unclear.