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1.
Nat Commun ; 11(1): 4954, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009396

RESUMO

Genetic variation is of crucial importance for crop improvement. Landraces are valuable sources of diversity, but for quantitative traits efficient strategies for their targeted utilization are lacking. Here, we map haplotype-trait associations at high resolution in ~1000 doubled-haploid lines derived from three maize landraces to make their native diversity for early development traits accessible for elite germplasm improvement. A comparative genomic analysis of the discovered haplotypes in the landrace-derived lines and a panel of 65 breeding lines, both genotyped with 600k SNPs, points to untapped beneficial variation for target traits in the landraces. The superior phenotypic performance of lines carrying favorable landrace haplotypes as compared to breeding lines with alternative haplotypes confirms these findings. Stability of haplotype effects across populations and environments as well as their limited effects on undesired traits indicate that our strategy has high potential for harnessing beneficial haplotype variation for quantitative traits from genetic resources.


Assuntos
Haplótipos/genética , Característica Quantitativa Herdável , Zea mays/genética , Biblioteca Gênica , Variação Genética , Genoma de Planta , Estudo de Associação Genômica Ampla , Haploidia , Melhoramento Vegetal , Análise de Componente Principal , Zea mays/crescimento & desenvolvimento
2.
PLoS One ; 15(9): e0237160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881879

RESUMO

Pareiorhaphis hystrix is a widely distributed species, occurring in the upper and middle Uruguay River and in the Taquari River basin, Patos Lagoon system, southern Brazil. Morphological variation has been detected throughout the distribution of P. hystrix, and this work seeks to test the conspecific nature of populations in several occurrence areas. Specimens from six areas in the Uruguay River basin and three in the Taquari River basin were compared. Variance analysis (ANOVA) was performed for the meristic data, and Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were conducted for morphometric data. Molecular analyses used coI, cytb, 12S and 16S mitochondrial genes, examining nucleotide diversity, haplotype diversity, genetic distance, and delimitation of possible multiple species through the Generalized Mixed Yule Coalescent (GMYC) method. Phylogenetic relationships of studied populations were also investigated through Bayesian inference. While PCA indicated a tendency of overlap between areas, ANOVA and LDA detected a subtle differentiation between populations from the two hydrographic basins. Yet, both latter analyses recovered the population from Pelotas River, a tributary to Uruguay River, as more similar to populations from Taquari River, which is congruent to morphological observations of anterior abdominal plates. The molecular data indicated a nucleotide diversity lower than the haplotypic diversity, suggestive of recent expansion. The concatenated haplotype network points to slight differentiation between areas, with each locality presenting unique and non-shared haplotypes, although with few mutational steps in general. The species delimitation by coalescence analysis suggested the presence of a variable number of OTUs depending on the inclusion or exclusion of an outgroup. In general, the morphological data suggest a subtle variation by river basin, while the genetic data indicates a weak population structuration by hydrographic areas, especially the Chapecó and Passo Fundo rivers. However, there is still not enough differentiation between the specimens to suggest multiple species. The iterative analyses indicate that Pareiorhaphis hystrix is composed of a single, although variable, species.


Assuntos
Peixes-Gato/anatomia & histologia , Peixes-Gato/classificação , Animais , Teorema de Bayes , Brasil , Peixes-Gato/genética , Análise Discriminante , Feminino , Genes Mitocondriais , Geografia , Haplótipos/genética , Masculino , Fenótipo , Filogenia , Pigmentação , Análise de Componente Principal , Rios , Especificidade da Espécie
3.
PLoS One ; 15(9): e0238255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936832

RESUMO

It was shown that the human Angiotensin-converting enzyme 2 (ACE2) is the receptor of recent coronavirus SARS-CoV-2, and variation in this gene may affect the susceptibility of a population. Therefore, we have analysed the sequence data of ACE2 among 393 samples worldwide, focusing on South Asia. Genetically, South Asians are more related to West Eurasian populations rather than to East Eurasians. In the present analyses of ACE2, we observed that the majority of South Asian haplotypes are closer to East Eurasians rather than to West Eurasians. The phylogenetic analysis suggested that the South Asian haplotypes shared with East Eurasians involved two unique event polymorphisms (rs4646120 and rs2285666). In contrast with the European/American populations, both of the SNPs have largely similar frequencies for East Eurasians and South Asians, Therefore, it is likely that among the South Asians, host susceptibility to the novel coronavirus SARS-CoV-2 will be more similar to that of East Eurasians rather than to that of Europeans.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Infecções por Coronavirus/genética , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Polimorfismo de Nucleotídeo Único , Receptores Virais/genética , Ásia/epidemiologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Haplótipos/genética , Migração Humana , Humanos , Desequilíbrio de Ligação , Pandemias , Filogenia , Pneumonia Viral/etnologia
4.
PLoS One ; 15(8): e0237916, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32842138

RESUMO

Highly spread through the Amazon River basin, Prochilodus nigricans have had its taxonomic validity recently questioned, when genetic differences between Western and Eastern Amazon populations from the Brazilian shield were detected. This area has been seeing as a region of high ichthyofaunal diversity and endemism, in which the hybrid origin of the Tapajós River basin has been raised. In this paper, we report a new molecular lineage within P. nigricans of Tapajós River, highlighting this region still hides taxonomically significant diversity. Haplotype networks were reconstructed using the mitochondrial COI and ATP6/8 markers, which were also used to calculate genetic distances among clusters. We additionally conducted a delimiting species approach by employing a Generalized Mixed Yule-Coalescent model (GMYC) with COI sequences produced here, and previous ones published for individuals sampled across the Amazon River basin. In addition to the genetic differentiation within P. nigricans, our findings favor the hypothesis of hybrid origin of the Tapajós River basin and reaffirm the importance of studies aiming to investigate hidden diversity to address taxonomic and biogeographic issues, that certainly benefit better biodiversity conservation actions.


Assuntos
Biodiversidade , Caraciformes/classificação , Caraciformes/genética , Filogenia , Rios , Animais , Teorema de Bayes , Brasil , Geografia , Haplótipos/genética
5.
PLoS One ; 15(8): e0237882, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845927

RESUMO

Phylogenetic positions of the genus Longgenacris and one of its members, i.e. L. rufiantennus are controversial. The species boundaries within both of L. rufiantennus+Fruhstorferiola tonkinensis and F. viridifemorata species groups are unclear. In this study, we explored the phylogenetic positions of the genus Longgenacris and the species L. rufiantennus and the relationships among F. viridifemorata group based on the 658-base fragment of the mitochondrial gene cytochrome c oxidase subunit I (COI) barcode and the complete sequences of the internal transcribed spacer regions (ITS1 and ITS2) of the nuclear ribosomal DNA. The phylogenies were reconstructed in maximum likelihood framework using IQ-TREE. K2P distances were used to assess the overlap range between intraspecific variation and interspecific divergence. Phylogenetic species concept and NJ tree, K2P distance, the statistical parsimony network as well as the generalized mixed Yule coalescent model (GMYC) were employed to delimitate the species boundaries in L. rufiantennus+F. tonkinensis and F. viridifemorata species groups. The results demonstrated that the genus Longgenacris should be placed in the subfamily Melanoplinae but not Catantopinae, and L. rufiantennus should be a member of the genus Fruhstorferiola but not Longgenacris. Species boundary delimitation confirmed the presence of oversplitting in L. rufiantennus+F. tonkinensis and F. viridifemorata species groups and suggested that each group should be treated as a single species.


Assuntos
Gafanhotos/classificação , Gafanhotos/genética , Filogenia , Animais , Complexo IV da Cadeia de Transporte de Elétrons/genética , Variação Genética , Gafanhotos/anatomia & histologia , Haplótipos/genética , Funções Verossimilhança , Masculino , Modelos Teóricos , Especificidade da Espécie , Dente/anatomia & histologia
6.
PLoS Med ; 17(8): e1003305, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841251

RESUMO

BACKGROUND: Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved. METHODS AND FINDINGS: Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits. CONCLUSIONS: We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.


Assuntos
Peso ao Nascer/fisiologia , Estatura/fisiologia , Estudo de Associação Genômica Ampla/métodos , Haplótipos/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Testes Genéticos/métodos , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos
7.
Gene ; 761: 145047, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32783993

RESUMO

Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.


Assuntos
Neoplasias da Mama/genética , Variações do Número de Cópias de DNA/genética , DNA Mitocondrial/genética , Adulto , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Haplótipos/genética , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Mitocôndrias/genética
8.
Gene ; 761: 145049, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32791092

RESUMO

Breast cancer (BRCA) is a highly heterogeneous disease due to the complicated microenvironment in the tumor, making the treatment benefits varied. Therefore, this study aims to identify a gene signature in the tumor microenvironment (TME) associated with the prognosis of BRCA patients. We downloaded the immune, stromal, and proliferation (ISP)-associated genes from the literature on BRCA. mRNA expression and clinical information obtained from The Cancer Genome Atlas (TCGA) were performed to identify the initial biomarker. Furthermore, we validated the robustness of the gene signature in the independent validation data set GSE20685. A four-gene signature in TME, including CD74, MMP9, RPA3, and SHCBP1, was constructed to predict the overall survival of BRCA. The survival time of the high-risk group was significantly worse than that of the low-risk group. Univariate and multivariate Cox regression analysis showed that our four-gene ISP signature was an independent prognostic factor in TCGA and GSE20685 data sets. The AUC suggested that our four-gene ISP signature was comparable to TNM classification at predicting the overall survival of BRCA patients. Interestingly, BRCA patients with high-risk scores were more likely to be associated with stromal and proliferation of cancer. In contrast, those with high-risk scores were more likely to be associated with tumor immunity-related pathway. We found an innovative biomarker in TME to predict the prognosis of BRCA. This signal might reflect the imbalance of TME and provide potential biomarkers for the individualized and precise treatment of BRCA.


Assuntos
Neoplasias da Mama/genética , Microambiente Tumoral/genética , Adulto , Antígenos CD/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/genética , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Haplótipos/genética , Humanos , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Fatores de Risco , Proteínas Adaptadoras da Sinalização Shc/genética , Sialiltransferases/genética
9.
Am J Hum Genet ; 107(3): 473-486, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32781046

RESUMO

Africa contains more human genetic variation than any other continent, but the majority of the population-scale analyses of the African peoples have focused on just two of the four major linguistic groups, the Niger-Congo and Afro-Asiatic, leaving the Nilo-Saharan and Khoisan populations under-represented. In order to assess genetic variation and signatures of selection within a Nilo-Saharan population and between the Nilo-Saharan and Niger-Congo and Afro-Asiatic, we sequenced 50 genomes from the Nilo-Saharan Lugbara population of North-West Uganda and 250 genomes from 6 previously unsequenced Niger-Congo populations. We compared these data to data from a further 16 Eurasian and African populations including the Gumuz, another putative Nilo-Saharan population from Ethiopia. Of the 21 million variants identified in the Nilo-Saharan population, 3.57 million (17%) were not represented in dbSNP and included predicted non-synonymous mutations with possible phenotypic effects. We found greater genetic differentiation between the Nilo-Saharan Lugbara and Gumuz populations than between any two Afro-Asiatic or Niger-Congo populations. F3 tests showed that Gumuz contributed a genetic component to most Niger-Congo B populations whereas Lugabara did not. We scanned the genomes of the Lugbara for evidence of selective sweeps. We found selective sweeps at four loci (SLC24A5, SNX13, TYRP1, and UVRAG) associated with skin pigmentation, three of which already have been reported to be under selection. These selective sweeps point toward adaptations to the intense UV radiation of the Sahel.


Assuntos
Adaptação Fisiológica/genética , Variação Genética/genética , Seleção Genética/genética , Pigmentação da Pele/genética , Grupo com Ancestrais do Continente Africano/genética , Antiporters/genética , Gerenciamento de Dados , Etiópia/epidemiologia , Feminino , Genética Populacional , Genoma Humano/genética , Haplótipos/genética , Humanos , Masculino , Glicoproteínas de Membrana/genética , Oxirredutases/genética , Polimorfismo de Nucleotídeo Único/genética , Nexinas de Classificação/genética , Proteínas Supressoras de Tumor/genética , Uganda/epidemiologia
10.
PLoS One ; 15(8): e0237928, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817637

RESUMO

We recently reported a family-based genome wide association study (GWAS) for pediatric stroke pointing our attention to two significantly associated genes of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family ADAMTS2 (rs469568, p = 8x10-6) and ADAMTS12 (rs1364044, p = 2.9x10-6). To further investigate these candidate genes, we applied a targeted resequencing approach on 48 discordant sib-pairs for pediatric stroke followed by genotyping of the detected non-synonymous variants in the full cohort of 270 offspring trios and subsequent fine mapping analysis. We identified eight non-synonymous SNPs in ADAMTS2 and six in ADAMTS12 potentially influencing the respective protein function. These variants were genotyped within a cohort of 270 affected offspring trios, association analysis revealed the ADAMTS12 variant rs77581578 to be significantly under-transmitted (p = 6.26x10-3) to pediatric stroke patients. The finding was validated in a pediatric venous thromboembolism (VTE) cohort of 189 affected trios. Subsequent haplotype analysis of ADAMTS12 detected a significantly associated haplotype comprising the originally identified GWAS variant. Several ADAMTS genes such as ADAMTS13 are involved in thromboembolic disease process. Here, we provide further evidence for ADAMTS12 to likely play a role in pediatric stroke. Further functional studies are warranted to assess the functional role of ADAMTS12 in the pathogenesis of stroke.


Assuntos
Proteínas ADAMTS/genética , Predisposição Genética para Doença , Acidente Vascular Cerebral/genética , Criança , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos/genética , Humanos , Masculino , Pediatria , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/patologia
11.
PLoS One ; 15(8): e0236759, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745105

RESUMO

The fall armyworm (Spodoptera frugiperda) is a moth pest native to the Western Hemisphere that has recently become a global problem, invading Africa, Asia, and Australia. The species has a broad host range, long-distance migration capability, and a propensity for the generation of pesticide resistance traits that make it a formidable invasive threat and a difficult pest to control. While fall armyworm migration has been extensively studied in North America, where annual migrations of thousands of kilometers are the norm, migration patterns in South America are less understood. As a first step to address this issue we have been genetically characterizing fall armyworm populations in Ecuador, a country in the northern portion of South America that has not been extensively surveyed for this pest. These studies confirm and extend past findings indicating similarities in the fall armyworm populations from Ecuador, Trinidad-Tobago, Peru, and Bolivia that suggest substantial migratory interactions. Specifically, we found that populations throughout Ecuador are genetically homogeneous, indicating that the Andes mountain range is not a long-term barrier to fall armyworm migration. Quantification of genetic variation in an intron sequence describe patterns of similarity between fall armyworm from different locations in South America with implications for how migration might be occurring. In addition, we unexpectedly found these observations only apply to one subset of fall armyworm (the C-strain), as the other group (R-strain) was not present in Ecuador. The results suggest differences in migration behavior between fall armyworm groups in South America that appear to be related to differences in host plant preferences.


Assuntos
Haplótipos/genética , Spodoptera/genética , Migração Animal , Animais , Equador , Complexo IV da Cadeia de Transporte de Elétrons/genética , Marcadores Genéticos , Íntrons/genética , Controle de Pragas , Filogenia , Filogeografia , América do Sul
12.
BMC Bioinformatics ; 21(Suppl 12): 304, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32703240

RESUMO

BACKGROUND: The imputation of genotypes increases the power of genome-wide association studies. However, the imputation quality should be assessed in each particular case. Nevertheless, not all imputation softwares control the error of output, e.g., the last release of fastPHASE program (1.4.8) lacks such an option. In this particular software there is also an uncertainty in choosing the model parameters. fastPHASE is based on haplotype clusters, which size should be set a priori. The parameter influences the results of imputation and downstream analysis. RESULTS: We present a software toolkit imputeqc to assess the imputation quality and/or to choose the model parameters for imputation. We demonstrate the efficacy of toolkit for evaluation of imputations made with both fastPHASE and BEAGLE software for HapMap and 1000 Genomes data. The discordance of genotypes received correlated well in both methods. Using imputeqc, we also shown how to choose the optimal number of haplotype clusters and expectation-maximization cycles for fastPHASE program. The found number of haplotype clusters of 25 was further applied for hapFLK testing that revealed signatures of selection at LCT region on chromosome 2. We also demonstrated how to decrease the computational time in the case of hapFLK testing from 3 days to 20 h. CONCLUSIONS: The toolkit is implemented as an R package imputeqc and command line scripts. The code is freely available at https://github.com/inzilico/imputeqc under the MIT license.


Assuntos
Estudo de Associação Genômica Ampla , Software , Cromossomos Humanos/genética , Bases de Dados Genéticas , Genoma Humano , Genótipo , Haplótipos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Tamanho da Amostra
13.
BMC Bioinformatics ; 21(Suppl 12): 306, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32703258

RESUMO

BACKGROUND: Graph-based representation of genome assemblies has been recently used in different contexts - from improved reconstruction of plasmid sequences and refined analysis of metagenomic data to read error correction and reference-free haplotype reconstruction. While many of these applications heavily utilize the alignment of long nucleotide sequences to assembly graphs, first general-purpose software tools for finding such alignments have been released only recently and their deficiencies and limitations are yet to be discovered. Moreover, existing tools can not perform alignment of amino acid sequences, which could prove useful in various contexts - in particular the analysis of metagenomic sequencing data. RESULTS: In this work we present a novel SPAligner (Saint-Petersburg Aligner) tool for aligning long diverged nucleotide and amino acid sequences to assembly graphs. We demonstrate that SPAligner is an efficient solution for mapping third generation sequencing reads onto assembly graphs of various complexity and also show how it can facilitate the identification of known genes in complex metagenomic datasets. CONCLUSIONS: Our work will facilitate accelerating the development of graph-based approaches in solving sequence to genome assembly alignment problem. SPAligner is implemented as a part of SPAdes tools library and is available on Github.


Assuntos
Algoritmos , Variação Genética , Alinhamento de Sequência , Sequência de Bases , Haplótipos/genética , Humanos , Software , Estatística como Assunto , beta-Lactamases/química
14.
Cytogenet Genome Res ; 160(5): 225-237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32659775

RESUMO

Loss of chromosome Y (LOY) is a mosaic aneuploidy that can be detected mainly in blood samples of male individuals. Usually, LOY occurrence increases with chronological age in healthy men. Moreover, recently LOY has been reported in association with several diseases, such as cancer, where its frequency is even higher. The Y chromosome is one of the shortest chromosomes of the human karyotype, and it is crucial for correct male development. This chromosome has functions beyond the male reproductive system, and loss of its genes or even LOY can have consequences for the male body that are yet to be elucidated. Analyses of the Y chromosome are largely applied in forensic contexts such as paternity testing, ancestry studies, and sexual assault cases, among others. Thus, LOY can be a disadvantage, limiting laboratory methods and result interpretation. However, as an advantage, LOY detection could be used as a biological age biomarker due to its association with the aging process. The potential application of LOY as biomarker highlights the necessity to clarify the molecular mechanism behind its occurrence and its possible applications in both health and forensic studies.


Assuntos
Aneuploidia , Cromossomos Humanos Y/genética , Medicina Legal , Marcadores Genéticos/genética , Saúde , Mosaicismo , Envelhecimento/genética , Haplótipos/genética , Humanos , Masculino , Paternidade , Delitos Sexuais
15.
BMC Evol Biol ; 20(1): 83, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660486

RESUMO

BACKGROUND: We have described the diversity of complete mtDNA sequences from 'relic' groups of the Russian Far East, primarily the Nivkhi (who speak a language isolate with no clear relatedness to any others) and Oroki of Sakhalin, as well as the sedentary Koryak from Kamchatka and the Udegey of Primorye. Previous studies have shown that most of their traditional territory was dramatically reshaped by the expansion of Tungusic-speaking groups. RESULTS: Overall, 285 complete mitochondrial sequences were selected for phylogenetic analyses of published, revised and new mitogenomes. To highlight the likely role of Neolithic expansions in shaping the phylogeographical landscape of the Russian Far East, we focus on the major East Eurasian maternal lineages (Y1a, G1b, D4m2, D4e5, M7a2, and N9b) that are restricted to the coastal area. To obtain more insight into autochthonous populations, we removed from the phylogeographic analysis the G2a, G3a2, M8a1, M9a1, and C4b1 lineages, also found within our samples, likely resulting from admixture between the expanding proto-Tungus and the indigenous Paleoasiatic groups with whom they assimilated. Phylogenetic analysis reveals that unlike the relatively diverse lineage spectrum observed in the Amur estuary and northwestern Sakhalin, the present-day subpopulation on the northeastern coast of the island is relatively homogenous: a sole Y1a sublineage, conspicuous for its nodal mutation at m.16189 T > C!, includes different haplotypes. Sharing of the Y1a-m.16189 T > C! sublineages and haplotypes among the Nivkhi, Ulchi and sedentary Koryak is also evident. Aside from Y1a, the entire tree approach expands our understanding of the evolutionary history of haplogroups G1, D4m, N9b, and M7a2. Specifically, we identified the novel haplogroup N9b1 in Primorye, which implies a link between a component of the Udegey ancestry and the Hokkaido Jomon. CONCLUSIONS: Through a comprehensive dataset of mitochondrial genomes retained in autochthonous populations along the coast between Primorye and the Bering Strait, we considerably extended the sequence diversity of these populations to provide new features based on the number and timing of founding lineages. We emphasize the value of integrating genealogical information with genetic data for reconstructing the population history of indigenous groups dramatically impacted by twentieth century resettlement and social upheavals.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Extinção Biológica , Genoma Mitocondrial , Grupos Populacionais/genética , Envelhecimento/genética , DNA Mitocondrial/genética , Genética Populacional , Geografia , Haplótipos/genética , Humanos , Ilhas , Filogenia , Filogeografia , Federação Russa
16.
Proc Natl Acad Sci U S A ; 117(29): 17130-17134, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32636262

RESUMO

Supergenes underlie striking polymorphisms in nature, yet the evolutionary mechanisms by which they arise and persist remain enigmatic. These clusters of linked loci can spread in populations because they captured coadapted alleles or by selfishly distorting the laws of Mendelian inheritance. Here, we show that the supergene haplotype associated with multiple-queen colonies in Alpine silver ants is a maternal effect killer. All eggs from heterozygous queens failed to hatch when they did not inherit this haplotype. Hence, the haplotype specific to multiple-queen colonies is a selfish genetic element that enhances its own transmission by causing developmental arrest of progeny that do not carry it. At the population level, such transmission ratio distortion favors the spread of multiple-queen colonies, to the detriment of the alternative haplotype associated with single-queen colonies. Hence, selfish gene drive by one haplotype will impact the evolutionary dynamics of alternative forms of colony social organization. This killer hidden in a social supergene shows that large nonrecombining genomic regions are prone to cause multifarious effects across levels of biological organization.


Assuntos
Formigas/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Genes de Insetos/genética , Herança Materna/genética , Comportamento Social , Animais , Formigas/crescimento & desenvolvimento , Formigas/fisiologia , Evolução Molecular , Feminino , Haplótipos/genética , Masculino , Meiose/genética , Sequências Reguladoras de Ácido Nucleico/genética , Sequências Repetitivas de Ácido Nucleico/genética
17.
DNA Cell Biol ; 39(7): 1356-1367, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32522041

RESUMO

Tuberculosis (TB) is an intricate infectious disease that causes a large number of deaths in the population. Interleukin (IL)-6 and IL-13 play functional roles in host resistance to Mycobacterium tuberculosis infection. Our aim in this study was to explore the association of IL-6 and IL-13 polymorphisms with TB susceptibility in the Western Chinese Han population. The case and control groups comprised 900 TB patients and 1534 healthy controls, respectively, and four single-nucleotide polymorphisms (SNPs) were genotyped in IL-6 and five SNPs in IL-13 through the improved multiplex ligation detection reaction method. We found no genetic variants in the IL-6 or IL-13 genes that were related to TB susceptibility in the analysis of alleles, genotypes, genetic models, and TB clinical subtypes, except for a trend toward low pulmonary tuberculosis and extrapulmonary tuberculosis susceptibility for the SNPs rs1295686 and rs20541. Our study did not find a link between IL-6 and IL-13 polymorphisms and TB susceptibility in the Western Chinese Han population. Therefore, our present data revealed the challenge of applying IL-6 and IL-13 SNPs as genetic markers for TB and that increased sample sizes and additional races are needed for further studies.


Assuntos
Predisposição Genética para Doença/genética , Interleucina-13/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Estudos de Casos e Controles , China/epidemiologia , Haplótipos/genética , Humanos , Tuberculose/epidemiologia
18.
Parasitol Res ; 119(7): 2347-2350, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32488623

RESUMO

Thelazia callipaeda (Spirurida, Thelaziidae) is a vector-borne zoonotic eyeworm able to infect a broad spectrum of carnivores. Here, we describe the first case of bilateral infection by T. callipaeda in the eyes of an adult female Iberian wolf (Canis lupus signatus) in central Spain. Nematodes collected were morphologically identified (n = 42), and two specimens were molecularly characterized. At the sequence analysis of the partial mitochondrial cytochrome c oxidase subunit 1 gene, T. callipaeda haplotype 1 (the only haplotype circulating in Europe) was detected. The role of the Iberian wolf as a natural reservoir for T. callipaeda in the life cycle of this emerging zoonosis and the implications in conservation are discussed.


Assuntos
Olho/parasitologia , Infecções por Spirurida/veterinária , Thelazioidea/isolamento & purificação , Lobos/parasitologia , Animais , Vetores de Doenças , Complexo IV da Cadeia de Transporte de Elétrons/genética , Europa (Continente) , Feminino , Genes Mitocondriais/genética , Haplótipos/genética , Humanos , Masculino , Espanha , Thelazioidea/genética , Zoonoses/parasitologia
19.
Am J Hum Genet ; 107(1): 96-110, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32589923

RESUMO

A recent genome-wide association study of Huntington disease (HD) implicated genes involved in DNA maintenance processes as modifiers of onset, including multiple genome-wide significant signals in a chr15 region containing the DNA repair gene Fanconi-Associated Nuclease 1 (FAN1). Here, we have carried out detailed genetic, molecular, and cellular investigation of the modifiers at this locus. We find that missense changes within or near the DNA-binding domain (p.Arg507His and p.Arg377Trp) reduce FAN1's DNA-binding activity and its capacity to rescue mitomycin C-induced cytotoxicity, accounting for two infrequent onset-hastening modifier signals. We also idenified a third onset-hastening modifier signal whose mechanism of action remains uncertain but does not involve an amino acid change in FAN1. We present additional evidence that a frequent onset-delaying modifier signal does not alter FAN1 coding sequence but is associated with increased FAN1 mRNA expression in the cerebral cortex. Consistent with these findings and other cellular overexpression and/or suppression studies, knockout of FAN1 increased CAG repeat expansion in HD-induced pluripotent stem cells. Together, these studies support the process of somatic CAG repeat expansion as a therapeutic target in HD, and they clearly indicate that multiple genetic variations act by different means through FAN1 to influence HD onset in a manner that is largely additive, except in the rare circumstance that two onset-hastening alleles are present. Thus, an individual's particular combination of FAN1 haplotypes may influence their suitability for HD clinical trials, particularly if the therapeutic agent aims to reduce CAG repeat instability.


Assuntos
Endodesoxirribonucleases/genética , Exodesoxirribonucleases/genética , Doença de Huntington/genética , Enzimas Multifuncionais/genética , Linhagem Celular , Estudo de Associação Genômica Ampla/métodos , Células HEK293 , Haplótipos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética
20.
Am J Hum Genet ; 107(1): 60-71, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32533944

RESUMO

Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment of GWAS loci and showed that the Sardinians remain significantly shorter than expected under neutrality (∼0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis of polygenic height scores, p = 3.89 × 10-4). We also found the trajectory of polygenic height scores between the Sardinian and the British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in the UK population by using a haplotype-based statistic, the trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10-4). In summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis.


Assuntos
Adaptação Fisiológica/genética , Estatura/genética , Herança Multifatorial/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Bancos de Espécimes Biológicos , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional/métodos , Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Haplótipos/genética , Humanos , Itália , Japão , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Seleção Genética/genética
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