RESUMO
Indigenous poultry breeds from Africa can survive in harsh tropical environments (such as long arid seasons, excessive rain and humidity, and extreme heat) and are resilient to disease challenges, but they are not productive compared to their commercial counterparts. Their adaptive characteristics are in response to natural selection or to artificial selection for production traits that have left selection signatures in the genome. Identifying these signatures of positive selection can provide insight into the genetic bases of tropical adaptations observed in indigenous poultry and thereby help to develop robust and high-performing breeds for extreme tropical climates. Here, we present the first large-scale whole-genome sequencing analysis of Nigerian indigenous chickens from different agro-climatic conditions, investigating their genetic diversity and adaptation to tropical hot climates (extreme arid and extreme humid conditions). The study shows a large extant genetic diversity but low level of population differentiation. Using different selection signature analyses, several candidate genes for adaptation were detected, especially in relation to thermotolerance and immune response (e.g., cytochrome P450 2B4-like, TSHR, HSF1, CDC37, SFTPB, HIF3A, SLC44A2, and ILF3 genes). These results have important implications for conserving valuable genetic resources and breeding improvement of chickens for thermotolerance.
Assuntos
Galinhas , Temperatura Alta , Animais , Galinhas/genética , Genoma , Genômica/métodos , Seleção Genética , Variação Genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Breeding for climate resilience is currently an important goal for sustainable livestock production. Local adaptations exhibited by indigenous livestock allow investigating the genetic control of this resilience. Ecological niche modeling (ENM) provides a powerful avenue to identify the main environmental drivers of selection. Here, we applied an integrative approach combining ENM with genome-wide selection signature analyses (XPEHH and Fst) and genotype-environment association (redundancy analysis), with the aim of identifying the genomic signatures of adaptation in African village chickens. By dissecting 34 agro-climatic variables from the ecosystems of 25 Ethiopian village chicken populations, ENM identified six key drivers of environmental challenges: One temperature variable-strongly correlated with elevation, three precipitation variables as proxies for water availability, and two soil/land cover variables as proxies of food availability for foraging chickens. Genome analyses based on whole-genome sequencing (n = 245), identified a few strongly supported genomic regions under selection for environmental challenges related to altitude, temperature, water scarcity, and food availability. These regions harbor several gene clusters including regulatory genes, suggesting a predominantly oligogenic control of environmental adaptation. Few candidate genes detected in relation to heat-stress, indicates likely epigenetic regulation of thermo-tolerance for a domestic species originating from a tropical Asian wild ancestor. These results provide possible explanations for the rapid past adaptation of chickens to diverse African agro-ecologies, while also representing new landmarks for sustainable breeding improvement for climate resilience. We show that the pre-identification of key environmental drivers, followed by genomic investigation, provides a powerful new approach for elucidating adaptation in domestic animals.
Assuntos
Galinhas , Ecossistema , Adaptação Fisiológica/genética , Animais , Galinhas/genética , Epigênese Genética , Genoma , GenômicaRESUMO
Macrophage colony-stimulating factor (CSF1 or M-CSF) and interleukin 34 (IL34) are secreted cytokines that control macrophage survival and differentiation. Both act through the CSF1 receptor (CSF1R), a type III transmembrane receptor tyrosine kinase. The functions of CSF1R and both ligands are conserved in birds. We have analyzed protein-coding sequence divergence among avian species. The intracellular tyrosine kinase domain of CSF1R was highly conserved in bird species as in mammals but the extracellular domain of avian CSF1R was more divergent in birds with multiple positively selected amino acids. Based upon crystal structures of the mammalian CSF1/IL34 receptor-ligand interfaces and structure-based alignments, we identified amino acids involved in avian receptor-ligand interactions. The contact amino acids in both CSF1 and CSF1R diverged among avian species. Ligand-binding domain swaps between chicken and zebra finch CSF1 confirmed the function of variants that confer species specificity on the interaction of CSF1 with CSF1R. Based upon genomic sequence analysis, we identified prevalent amino acid changes in the extracellular domain of CSF1R even within the chicken species that distinguished commercial broilers and layers and tropically adapted breeds. The rapid evolution in the extracellular domain of avian CSF1R suggests that at least in birds this ligand-receptor interaction is subjected to pathogen selection. We discuss this finding in the context of expression of CSF1R in antigen-sampling and antigen-presenting cells.
Assuntos
Evolução Biológica , Interleucinas/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , Polimorfismo Genético , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Animais , Galinhas , Interleucinas/genética , Ligantes , Fator Estimulador de Colônias de Macrófagos/genética , Filogenia , Receptor de Fator Estimulador de Colônias de Macrófagos/genética , Especificidade da Espécie , Peixe-ZebraRESUMO
There is increasing recognition that the underlying genetic variation contributing to complex traits influences transcriptional regulation and can be detected at a population level as expression quantitative trait loci. At the level of an individual, allelic variation in transcriptional regulation of individual genes can be detected by measuring allele-specific expression in RNAseq data. We reasoned that extreme variants in gene expression could be identified by analysis of inbred progeny with shared grandparents. Commercial chickens have been intensively selected for production traits. Selection is associated with large blocks of linkage disequilibrium with considerable potential for co-selection of closely linked "hitch-hiker alleles" affecting traits unrelated to the feature being selected, such as immune function, with potential impact on the productivity and welfare of the animals. To test this hypothesis that there is extreme allelic variation in immune-associated genes we sequenced a founder population of commercial broiler and layer birds. These birds clearly segregated genetically based upon breed type. Each genome contained numerous candidate null mutations, protein-coding variants predicted to be deleterious and extensive non-coding polymorphism. We mated selected broiler-layer pairs then generated cohorts of F2 birds by sibling mating of the F1 generation. Despite the predicted prevalence of deleterious coding variation in the genomic sequence of the founders, clear detrimental impacts of inbreeding on survival and post-hatch development were detected in only one F2 sibship of 15. There was no effect on circulating leukocyte populations in hatchlings. In selected F2 sibships we performed RNAseq analysis of the spleen and isolated bone marrow-derived macrophages (with and without lipopolysaccharide stimulation). The results confirm the predicted emergence of very large differences in expression of individual genes and sets of genes. Network analysis of the results identified clusters of co-expressed genes that vary between individuals and suggested the existence of trans-acting variation in the expression in macrophages of the interferon response factor family that distinguishes the parental broiler and layer birds and influences the global response to lipopolysaccharide. This study shows that the impact of inbreeding on immune cell gene expression can be substantial at the transcriptional level, and potentially opens a route to accelerate selection using specific alleles known to be associated with desirable expression levels.
RESUMO
In macrolecithal species, cryopreservation of the oocyte and zygote is not possible due to the large size and quantity of lipid deposited within the egg. For birds, this signifies that cryopreserving and regenerating a species from frozen cellular material are currently technically unfeasible. Diploid primordial germ cells (PGCs) are a potential means to freeze down the entire genome and reconstitute an avian species from frozen material. Here, we examine the use of genetically engineered (GE) sterile female layer chicken as surrogate hosts for the transplantation of cryopreserved avian PGCs from rare heritage breeds of chicken. We first amplified PGC numbers in culture before cryopreservation and subsequent transplantation into host GE embryos. We found that all hatched offspring from the chimera GE hens were derived from the donor rare heritage breed broiler PGCs, and using cryopreserved semen, we were able to produce pure offspring. Measurement of the mutation rate of PGCs in culture revealed that 2.7 × 10-10 de novo single-nucleotide variants (SNVs) were generated per cell division, which is comparable with other stem cell lineages. We also found that endogenous avian leukosis virus (ALV) retroviral insertions were not mobilized during in vitro propagation. Taken together, these results show that mutation rates are no higher than normal stem cells, essential if we are to conserve avian breeds. Thus, GE sterile avian surrogate hosts provide a viable platform to conserve and regenerate avian species using cryopreserved PGCs.
Assuntos
Animais Geneticamente Modificados/genética , Cruzamento/métodos , Galinhas/genética , Células Germinativas/citologia , Infertilidade/veterinária , Animais , Animais Geneticamente Modificados/fisiologia , Galinhas/fisiologia , Criopreservação , Diploide , Transferência Embrionária , Feminino , Edição de Genes , Engenharia Genética , MasculinoRESUMO
Several Romanian hospitals have noted increasing isolation of Providencia stuartii strains in recent years, with an alarming rate of carbapenem resistance. In order to provide molecular epidemiological data regarding their dissemination, 77 P. stuartii strains collected from five hospitals located in different regions of Romania were analysed. All strains harboured IncA/C plasmid, and 67 carried the blaNDM-1 gene. Six clonal clusters were differentiated by pulsed-field gel electrophoresis. The predominant subtype was found in all five hospitals. Our study highlights the need for efficient infection-control measures, the optimization of antibiotic use and the targeted surveillance for carbapenemase-producing P. stuartii.
Assuntos
Infecção Hospitalar/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Providencia/enzimologia , Providencia/isolamento & purificação , beta-Lactamases/genética , Infecção Hospitalar/transmissão , Infecções por Enterobacteriaceae/transmissão , Genótipo , Hospitais , Humanos , Epidemiologia Molecular , Tipagem Molecular , Plasmídeos/análise , Providencia/classificação , Providencia/genética , Romênia/epidemiologiaRESUMO
The feasibility of simultaneous treatment of multiple wastes via co-digestion was studied in semi-continuous mode at mesophilic conditions. The obtained results indicated that sewage sludge, organic fraction of municipal waste (OFMSW) and grease trap sludge (GTS) possess complementary properties that can be combined for successful anaerobic digestion. During the co-digestion period, methane yield and VS removal were significantly higher in comparison to digestion of sewage sludge alone. Addition of GTS to digesters treating sewage sludge resulted in increased VS removal and methane yield up to 13% (from 50 to 56.4) and 52% (from 300 to 456,547m3/Mg VSadd), respectively. While the use of OFMSW as the next co-substrate in the feedstock, can boost methane yield and VS removal up to 82% (300-547m3/Mg VSadd) and approximately 29% (from 50% to 64.7%), respectively. Moreover, the results of the present laboratory study revealed that the addition of co-substrates to the feedstock had a significant influence on biogas composition. During the experiment methane content in biogas ranged from 67% to 69%. While, the concentration of LCFAs was increasing with the gradual increase in the share of co-substrates in the mixtures, wherein only the oleic acid was higher than some inhibition concentrations which have been reported in the literature. However, it did not significantly affect the efficiency of the co-digestion process.
Assuntos
Reatores Biológicos , Esgotos , Resíduos Sólidos , Gerenciamento de Resíduos/métodos , Anaerobiose , Biocombustíveis/análise , Análise da Demanda Biológica de Oxigênio , Carbono/análise , Lipídeos , Metano/análise , Nitrogênio/análise , Poluentes da Água/análiseRESUMO
BACKGROUND: Infectious Pancreatic Necrosis (IPN) is a highly contagious birnavirus disease of farmed salmonid fish, which often causes high levels of morbidity and mortality. A large host genetic component to resistance has been previously described for Atlantic salmon (Salmo salar L.), which mediates high mortality rates in some families and zero mortality in others. However, the molecular and immunological basis for this resistance is not yet fully known. This manuscript describes a global comparison of the gene expression profiles of resistant and susceptible Atlantic salmon fry following challenge with the IPN virus. RESULTS: Salmon fry from two IPNV-resistant and two IPNV-susceptible full sibling families were challenged with the virus and sampled at 1 day, 7 days and 20 days post-challenge. Significant viral titre was observed in both resistant and susceptible fish at all timepoints, although generally at higher levels in susceptible fish. Gene expression profiles combined with gene ontology and pathway analyses demonstrated that while a clear immune response was observed in both resistant and susceptible fish, there were striking differences between the two phenotypes. The susceptible fish showed marked up-regulation of genes related to cytokine activity and inflammatory response that evidently failed to protect against the virus. In contrast, the resistant fish demonstrated a less pronounced immune response including up-regulation of genes relating to the M2 macrophage system. CONCLUSIONS: While only the susceptible phenotype shows appreciable mortality levels, both resistant and susceptible fish can become infected with IPNV. Susceptible fish are characterized by a much larger, yet ineffective, immune response, largely related to cytokine and inflammatory systems. Resistant fish demonstrate a more moderate, putative macrophage-mediated inflammatory response, which may contribute to their survival.
Assuntos
Infecções por Birnaviridae/veterinária , Resistência à Doença/genética , Doenças dos Peixes/genética , Salmo salar/genética , Salmo salar/imunologia , Animais , Infecções por Birnaviridae/genética , Infecções por Birnaviridae/imunologia , Citocinas/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Vírus da Necrose Pancreática Infecciosa , Macrófagos/imunologia , Salmo salar/virologia , TranscriptomaRESUMO
The environmental behaviour of antimony (Sb) is gathering attention due to its increasingly extensive use in various products, particularly in plastics. Because of this it may be expected that plastic waste is an emission source for Sb in the environment. This study presents a comprehensive field investigation of Sb concentrations in diverse types of waste from waste handling facilities in Norway. The wastes included waste electrical and electronic equipment (WEEE), glass, vehicle fluff, combustibles, bottom ash, fly ash and digested sludge. The highest solid Sb concentrations were found in WEEE and vehicle plastic (from 1238 to 1715 mg kg(-1)) and vehicle fluff (from 34 to 4565 mg kg(-1)). The type of acid used to digest the diverse solid waste materials was also tested. It was found that HNO3:HCl extraction gave substantially lower, non-quantitative yields compared to HNO3:HF. The highest water-leachable concentration for wastes when mixed with water at a 1 : 10 ratio were observed for plastic (from 0.6 to 2.0 mg kg(-1)) and bottom ash (from 0.4 to 0.8 mg kg(-1)). For all of the considered waste fractions, Sb(v) was the dominant species in the leachates, even though Sb(iii) as Sb2O3 is mainly used in plastics and other products, indicating rapid oxidation in water. This study also presents for the first time a comparison of Sb concentrations in leachate at waste handling facilities using both active grab samples and DGT passive samples. Grab samples target the total suspended Sb, whereas DGT targets the sum of free- and other chemically labile species. The grab sample concentrations (from 0.5 to 50 µg L(-1)) were lower than the predicted no-effect concentration (PNEC) of 113 µg L(-1). The DGT concentrations were substantially lower (from 0.05 to 9.93 µg L(-1)) than the grab samples, indicating much of the Sb is present in a non-available colloidal form. In addition, air samples were taken from the chimney and areas within combustible waste incinerators, as well as from the vent of WEEE sorting facility. The WEEE vent had the highest Sb concentration (from <100 to 2200 ng m(-3)), which were orders of magnitude higher than the air surrounding the combustible shredder (from 25 to 217 ng m(-3)), and the incinerator chimney (from <30 to 100 ng m(-3)). From these results, it seems evident that Sb from waste is not an environmental concern in Norway, and that Sb is mostly readily recovered from plastic and bottom ash.
Assuntos
Antimônio/análise , Monitoramento Ambiental , Eliminação de Resíduos/métodos , Resíduos/análise , Poluentes Químicos da Água/análise , Noruega , Esgotos/químicaRESUMO
BACKGROUND: Small insertions and deletions (InDels) constitute the second most abundant class of genetic variants and have been found to be associated with many traits and diseases. The present study reports on the detection and characterisation of about 883 K high quality InDels from the whole-genome analysis of several modern layer chicken lines from diverse breeds. RESULTS: To reduce the error rates seen in InDel detection, this study used the consensus set from two InDel-calling packages: SAMtools and Dindel, as well as stringent post-filtering criteria. By analysing sequence data from 163 chickens from 11 commercial and 5 experimental layer lines, this study detected about 883 K high quality consensus InDels with 93% validation rate and an average density of 0.78 InDels/kb over the genome. Certain chromosomes, viz, GGAZ, 16, 22 and 25 showed very low densities of InDels whereas the highest rate was observed on GGA6. In spite of the higher recombination rates on microchromosomes, the InDel density on these chromosomes was generally lower relative to macrochromosomes possibly due to their higher gene density. About 43-87% of the InDels were found to be fixed within each line. The majority of detected InDels (86%) were 1-5 bases and about 63% were non-repetitive in nature while the rest were tandem repeats of various motif types. Functional annotation identified 613 frameshift, 465 non-frameshift and 10 stop-gain/loss InDels. Apart from the frameshift and stopgain/loss InDels that are expected to affect the translation of protein sequences and their biological activity, 33% of the non-frameshift were predicted as evolutionary intolerant with potential impact on protein functions. Moreover, about 2.5% of the InDels coincided with the most-conserved elements previously mapped on the chicken genome and are likely to define functional elements. InDels potentially affecting protein function were found to be enriched for certain gene-classes e.g. those associated with cell proliferation, chromosome and Golgi organization, spermatogenesis, and muscle contraction. CONCLUSIONS: The large catalogue of InDels presented in this study along with their associated information such as functional annotation, estimated allele frequency, etc. are expected to serve as a rich resource for application in future research and breeding in the chicken.
Assuntos
Galinhas/genética , Genoma , Mutação INDEL/genética , Deleção de Sequência/genética , Sequência de Aminoácidos , Animais , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Galinhas/genética , Cromossomos/genética , Animais , Galinhas/classificação , Galinhas/fisiologia , Mapeamento Cromossômico , Metilação de DNA , Evolução Molecular , Feminino , Perfilação da Expressão Gênica , Variação Genética , Genômica/métodos , Hibridização in Situ Fluorescente/métodos , Masculino , Anotação de Sequência Molecular , FilogeniaRESUMO
Next-generation sequencing has prompted a surge of discovery of millions of genetic variants from vertebrate genomes. Besides applications in genetic association and linkage studies, a fraction of these variants will have functional consequences. This study describes detection and characterization of 15 million SNPs from chicken genome with the goal to predict variants with potential functional implications (pfVars) from both coding and non-coding regions. The study reports: 183K amino acid-altering SNPs of which 48% predicted as evolutionary intolerant, 13K splicing variants, 51K likely to alter RNA secondary structures, 500K within most conserved elements and 3K from non-coding RNAs. Regions of local fixation within commercial broiler and layer lines were investigated as potential selective sweeps using genome-wide SNP data. Relationships with phenotypes, if any, of the pfVars were explored by overlaying the sweep regions with known QTLs. Based on this, the candidate genes and/or causal mutations for a number of important traits are discussed. Although the fixed variants within sweep regions were enriched with non-coding SNPs, some non-synonymous-intolerant mutations reached fixation, suggesting their possible adaptive advantage. The results presented in this study are expected to have important implications for future genomic research to identify candidate causal mutations and in poultry breeding.
Assuntos
Proteínas Aviárias/genética , Galinhas/genética , Genoma , Polimorfismo de Nucleotídeo Único , Alelos , Animais , Genética Populacional , Locos de Características Quantitativas , RNA/química , RNA/genéticaRESUMO
The review encompasses the historical background, chemical composition of miswak (Salvadora persica) and the effects it has on oral health. Miswak is an Arabic word meaning "tooth cleaning stick" and is a natural toothbrush made from the twigs of Salvadora persica (S. persica). Not only is S. persica miswak used in several countries throughout the world, but in some cases, it has proved to be more beneficial as compared to its counterparts-a toothbrush and toothpaste. Additionally, how to prepare the miswak, proper use of it, and the techniques to use will be discussed. An overview of the antimicrobial, anticariogenic, antiplaque, and antigingivitis effects of miswak on oral health will be given in the context of in vitro experiments and clinical trials. Lastly, various oral hygiene studies will be discussed, in order to identify a common denominator between modern-day and the age-old practice of miswak. Recent scientific evidence regarding its probiotic role, cell viability and comparative cytotoxicity and future research trends would be highlighted. Miswak, a cultural and history-based oral hygiene tool is now being evaluated on scientific evidence. Through comparing the naturally-occurring and scientific evolution of S. persica's usage, we will be able to better understand the uniqueness of miswak, relative to that of other oral hygiene tools as being a solo oral hygiene tool of a significant part of the World population. It's hope that the review would help health care professionals to have better knowledge and awareness about miswak, to improve the quality of life of their culturally diverse patients population who are uninitiated for regular oral hygiene measures due to various constraints. The use of miswak can be added to the notion of primary health care approach (PHCA) and oral health promotion.
Assuntos
Higiene Bucal/instrumentação , Caules de Planta , Salvadoraceae , Humanos , Fitoterapia/instrumentação , Extratos Vegetais/uso terapêutico , Salvadoraceae/química , Escovação Dentária/instrumentaçãoRESUMO
Advent of microarray technologies revolutionized the nature and scope of genetic and genomic research in human and other species by allowing massively parallel analysis of thousands of genomic sites. They have been used for diverse purposes such as for transcriptome analysis, CNV detection, SNP and CNV genotyping, studying DNA-protein interaction, and detection of genome methylation. Microarrays have also made invaluable contributions to research in chicken which is an important model organism for studying embryology, immunology, oncology, virology, evolution, genetics, and genomics and also for other avian species. Despite their huge contributions in life science research, the future of microarrays is now being questioned with the advent of massively parallel next generation sequencing (NGS) technologies, which promise to overcome some of the limitations of microarray platforms. In this article we review the various microarray resources developed for chicken and their past and potential future applications. We also discuss about the future of microarrays in the NGS era particularly in the context of livestock genetics. We argue that even though NGS promises some major advantages-in particular, offers the opportunity to discover novel elements in the genome-microarrays will continue to be major tools for research and practice in the field of livestock genetics/genomics due to their affordability, high throughput nature, mature established technologies and ease of application. Moreover, with advent of new microarray technologies like capture arrays, the NGS and microarrays are expected to complement each other in future research in life science.
Assuntos
Galinhas/genética , Genômica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Animais , Sequenciamento de Nucleotídeos em Larga Escala , Gado/genéticaRESUMO
BACKGROUND: High density (HD) SNP genotyping arrays are an important tool for genetic analyses of animals and plants. Although the chicken is one of the most important farm animals, no HD array is yet available for high resolution genetic analysis of this species. RESULTS: We report here the development of a 600 K Affymetrix® Axiom® HD genotyping array designed using SNPs segregating in a wide variety of chicken populations. In order to generate a large catalogue of segregating SNPs, we re-sequenced 243 chickens from 24 chicken lines derived from diverse sources (experimental, commercial broiler and layer lines) by pooling 10-15 samples within each line. About 139 million (M) putative SNPs were detected by mapping sequence reads to the new reference genome (Gallus_gallus_4.0) of which ~78 M appeared to be segregating in different lines. Using criteria such as high SNP-quality score, acceptable design scores predicting high conversion performance in the final array and uniformity of distribution across the genome, we selected ~1.8 M SNPs for validation through genotyping on an independent set of samples (n = 282). About 64% of the SNPs were polymorphic with high call rates (>98%), good cluster separation and stable Mendelian inheritance. Polymorphic SNPs were further analysed for their population characteristics and genomic effects. SNPs with extreme breach of Hardy-Weinberg equilibrium (P < 0.00001) were excluded from the panel. The final array, designed on the basis of these analyses, consists of 580,954 SNPs and includes 21,534 coding variants. SNPs were selected to achieve an essentially uniform distribution based on genetic map distance for both broiler and layer lines. Due to a lower extent of LD in broilers compared to layers, as reported in previous studies, the ratio of broiler and layer SNPs in the array was kept as 3:2. The final panel was shown to genotype a wide range of samples including broilers and layers with over 100 K to 450 K informative SNPs per line. A principal component analysis was used to demonstrate the ability of the array to detect the expected population structure which is an important pre-investigation step for many genome-wide analyses. CONCLUSIONS: This Affymetrix® Axiom® array is the first SNP genotyping array for chicken that has been made commercially available to the public as a product. This array is expected to find widespread usage both in research and commercial application such as in genomic selection, genome-wide association studies, selection signature analyses, fine mapping of QTLs and detection of copy number variants.
Assuntos
Galinhas/genética , Técnicas de Genotipagem/instrumentação , Polimorfismo de Nucleotídeo Único/genética , Animais , Artefatos , Biologia Computacional , Frequência do Gene , Masculino , Reprodutibilidade dos Testes , Análise de SequênciaRESUMO
BACKGROUND: While basal cell carcinoma (BCC) remains the most common skin cancer, the incidence of metastasis is rare. Most cases of metastatic BCC have been to regional lymph nodes. Metastasis to bone marrow with myelophthisic anemia is especially rare. To our knowledge, there have been only 5 reported cases in literature. We report a sixth case. OBSERVATIONS: A 46-year-old male patient presented with an 8 × 7-cm ulcerated plaque on his chest, found to be morpheaform basal cell on pathology. Laboratory findings were notable for normocytic anemia, thrombocytopenia, and elevated LDH. Further work up with bone marrow biopsy revealed tumor cells staining positive for CK AE1/AE3, BerEP4, CK7, CD56, and PIN-4. This confirmed the diagnosis of metastatic BCC (MBCC) to bone marrow. CONCLUSIONS: Although the rate of metastasis for BCC is rare, once it occurs, prognosis is poor. MBCC remains a challenge to treat. Therefore, it is critical to resolve the primary BCC and obtain vigilant follow-up, especially in patients with multiple risk factors for MBCC.
Assuntos
Anemia Mielopática/etiologia , Neoplasias da Medula Óssea/complicações , Neoplasias da Medula Óssea/secundário , Carcinoma Basocelular/secundário , Neoplasias Cutâneas/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In most studies aimed at localizing footprints of past selection, outliers at tails of the empirical distribution of a given test statistic are assumed to reflect locus-specific selective forces. Significance cutoffs are subjectively determined, rather than being related to a clear set of hypotheses. Here, we define an empirical p-value for the summary statistic by means of a permutation method that uses the observed SNP structure in the real data. To illustrate the methodology, we applied our approach to a panel of 2.9 million autosomal SNPs identified from re-sequencing a pool of 15 individuals from a brown egg layer line. We scanned the genome for local reductions in heterozygosity, suggestive of selective sweeps. We also employed a modified sliding window approach that accounts for gaps in the sequence and increases scanning resolution by moving the overlapping windows by steps of one SNP only, and suggest to call this a "creeping window" strategy. The approach confirmed selective sweeps in the region of previously described candidate genes, i.e. TSHR, PRL, PRLHR, INSR, LEPR, IGF1, and NRAMP1 when used as positive controls. The genome scan revealed 82 distinct regions with strong evidence of selection (genome-wide p-value<0.001), including genes known to be associated with eggshell structure and immune system such as CALB1 and GAL cluster, respectively. A substantial proportion of signals was found in poor gene content regions including the most extreme signal on chromosome 1. The observation of multiple signals in a highly selected layer line of chicken is consistent with the hypothesis that egg production is a complex trait controlled by many genes.
Assuntos
Galinhas/genética , Estudo de Associação Genômica Ampla , Seleção Genética , Animais , Simulação por Computador , Feminino , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Reprodutibilidade dos TestesRESUMO
The uptake of 109Cd and 65Zn and their stable isotopes by ryegrass (Lolium multiflorum Lam.), grown on two different soil types, was investigated in climatically controlled growth chambers at 9 and 21 degrees C. The soils were treated with 0 and 4% organic matter (pig [Sus scrofa] manure) and spiked with 109Cd and 65Zn before sowing. The organic matter addition resulted in increased uptake of the 109Cd, Cd, and Zn by ryegrass, but the uptake of 65Zn was decreased. The latter effect was ascribed to isotopic dilution of 65Zn as the amount of stable Zn in the plant tissues increased with the organic matter addition. The effect of temperature was more pronounced than that of organic matter addition, and the uptake of both 109Cd and 65Zn and their stable isotopes was higher in ryegrass grown at 21 degrees C than that grown at 9 degrees C. Results from fractionation and speciation analysis of soil cadmium and zinc were correlated with plant uptake, and there was a good consistency between observed plant uptake and the physico-chemical forms of cadmium and zinc in soil and soil solution presumed to be plant available.