Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.329
Filtrar
1.
Nat Commun ; 11(1): 4374, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873787

RESUMO

Oncogene amplification, a major driver of cancer pathogenicity, is often mediated through focal amplification of genomic segments. Recent results implicate extrachromosomal DNA (ecDNA) as the primary driver of focal copy number amplification (fCNA) - enabling gene amplification, rapid tumor evolution, and the rewiring of regulatory circuitry. Resolving an fCNA's structure is a first step in deciphering the mechanisms of its genesis and the fCNA's subsequent biological consequences. We introduce a computational method, AmpliconReconstructor (AR), for integrating optical mapping (OM) of long DNA fragments (>150 kb) with next-generation sequencing (NGS) to resolve fCNAs at single-nucleotide resolution. AR uses an NGS-derived breakpoint graph alongside OM scaffolds to produce high-fidelity reconstructions. After validating its performance through multiple simulation strategies, AR reconstructed fCNAs in seven cancer cell lines to reveal the complex architecture of ecDNA, a breakage-fusion-bridge and other complex rearrangements. By reconstructing the rearrangement signatures associated with an fCNA's generative mechanism, AR enables a more thorough understanding of the origins of fCNAs.


Assuntos
Amplificação de Genes , Genômica/métodos , Neoplasias/genética , Oncogenes/genética , Linhagem Celular Tumoral , Mapeamento Cromossômico/métodos , Análise Citogenética , Genoma Humano/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
2.
PLoS One ; 15(8): e0238245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845907

RESUMO

To study the detection limits of chromosomal microaberrations in non-invasive prenatal testing with aim for five target microdeletion syndromes, including DiGeorge, Prader-Willi/Angelman, 1p36, Cri-Du-Chat, and Wolf-Hirschhorn syndromes. We used known cases of pathogenic deletions from ISCA database to specifically define regions critical for the target syndromes. Our approach to detect microdeletions, from whole genome sequencing data, is based on sample normalization and read counting for individual bins. We performed both an in-silico study using artificially created data sets and a laboratory test on mixed DNA samples, with known microdeletions, to assess the sensitivity of prediction for varying fetal fractions, deletion lengths, and sequencing read counts. The in-silico study showed sensitivity of 79.3% for 10% fetal fraction with 20M read count, which further increased to 98.4% if we searched only for deletions longer than 3Mb. The test on laboratory-prepared mixed samples was in agreement with in-silico results, while we were able to correctly detect 24 out of 29 control samples. Our results suggest that it is possible to incorporate microaberration detection into basic NIPT as part of the offered screening/diagnostics procedure, however, accuracy and reliability depends on several specific factors.


Assuntos
Mapeamento Cromossômico/métodos , Limite de Detecção , Teste Pré-Natal não Invasivo/métodos , Sequenciamento Completo do Genoma/métodos , Ácidos Nucleicos Livres/análise , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 1/genética , Síndrome do Miado do Gato/diagnóstico , Síndrome do Miado do Gato/genética , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Feminino , Humanos , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Gravidez , Cuidado Pré-Natal , Síndrome de Wolf-Hirschhorn/diagnóstico , Síndrome de Wolf-Hirschhorn/genética
3.
Nat Commun ; 11(1): 3294, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620744

RESUMO

Systemic lupus erythematosus (SLE) is mediated by autoreactive antibodies that damage multiple tissues. Genome-wide association studies (GWAS) link >60 loci with SLE risk, but the causal variants and effector genes are largely unknown. We generated high-resolution spatial maps of SLE variant accessibility and gene connectivity in human follicular helper T cells (TFH), a cell type required for anti-nuclear antibodies characteristic of SLE. Of the ~400 potential regulatory variants identified, 90% exhibit spatial proximity to genes distant in the 1D genome sequence, including variants that loop to regulate the canonical TFH genes BCL6 and CXCR5 as confirmed by genome editing. SLE 'variant-to-gene' maps also implicate genes with no known role in TFH/SLE disease biology, including the kinases HIPK1 and MINK1. Targeting these kinases in TFH inhibits production of IL-21, a cytokine crucial for class-switched B cell antibodies. These studies offer mechanistic insight into the SLE-associated regulatory architecture of the human genome.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Linfócitos T Auxiliares-Indutores/metabolismo , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Células Cultivadas , Mapeamento Cromossômico/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Células Jurkat , Lúpus Eritematoso Sistêmico/imunologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Interferência de RNA , Receptores CXCR5/genética , Linfócitos T Auxiliares-Indutores/imunologia
4.
Nat Commun ; 11(1): 3613, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680994

RESUMO

Common fragile sites (CFSs) are regions susceptible to replication stress and are hotspots for chromosomal instability in cancer. Several features were suggested to underlie CFS instability, however, these features are prevalent across the genome. Therefore, the molecular mechanisms underlying CFS instability remain unclear. Here, we explore the transcriptional profile and DNA replication timing (RT) under mild replication stress in the context of the 3D genome organization. The results reveal a fragility signature, comprised of a TAD boundary overlapping a highly transcribed large gene with APH-induced RT-delay. This signature enables precise mapping of core fragility regions in known CFSs and identification of novel fragile sites. CFS stability may be compromised by incomplete DNA replication and repair in TAD boundaries core fragility regions leading to genomic instability. The identified fragility signature will allow for a more comprehensive mapping of CFSs and pave the way for investigating mechanisms promoting genomic instability in cancer.


Assuntos
Sítios Frágeis do Cromossomo/genética , Período de Replicação do DNA/genética , Genoma Humano , Instabilidade Genômica , Afidicolina/farmacologia , Linhagem Celular , Sequenciamento de Cromatina por Imunoprecipitação , Mapeamento Cromossômico/métodos , DNA/química , Período de Replicação do DNA/efeitos dos fármacos , Fibroblastos , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias/genética , Conformação de Ácido Nucleico , Sensibilidade e Especificidade , Transcrição Genética/efeitos dos fármacos
5.
PLoS One ; 15(6): e0234335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516348

RESUMO

Shoot fly (Atherigona naqvii) is one of the major insects affecting spring maize in North India and can cause yield loss up to 60 per cent. The genetics of insect resistance is complex as influenced by genotypic background, insect population and climatic conditions. Therefore, quantitative trait loci (QTL) mapping is a highly effective approach for studying genetically complex forms of insect resistance. The objective of the present study was to dissect the genetic basis of resistance and identification of genomic regions associated with shoot fly resistance. A total of 107 F2 population derived from the cross CM143 (resistant) x CM144 (susceptible) was genotyped with 120 SSR markers. Phenotypic data were recorded on replicated F2:3 progenies for various component traits imparting resistance to shoot fly at different time intervals. Resistance to shoot fly was observed to be under polygenic control as evidenced by the identification of 19 putative QTLs governed by overdominance to partial dominance and additive gene actions. The major QTLs conditioning shoot fly resistance viz., qDH9.1 (deadheart) and qEC9.1 (oviposition) explaining 15.03 and 18.89 per cent phenotypic variance, respectively were colocalized on chromosome 9. These QTLs are syntenic to regions of chromosome 10 of sorghum which were also accounted for deadheart and oviposition suggesting that the same gene block may be responsible for shoot fly resistance. The candidate genes such as cysteine protease, subtilisin-chymotrypsin inhibitor, cytochrome P450 involved in synthesis of alleochemicals, receptor kinases, glossy15 and ubiquitin-proteasome degradation pathway were identified within the predicted QTL regions. This is the first reported mapping of QTLs conferring resistance to shoot fly in maize, and the markers identified here will be a valuable resource for developing elite maize cultivars with resistance to shoot fly.


Assuntos
Resistência à Doença/genética , Sorghum/genética , Zea mays/genética , Animais , Mapeamento Cromossômico/métodos , Grão Comestível/genética , Genômica/métodos , Genótipo , Índia , Insetos , Repetições de Microssatélites/genética , Controle Biológico de Vetores/métodos , Fenótipo , Doenças das Plantas/genética , Locos de Características Quantitativas/genética
6.
PLoS One ; 15(6): e0233377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502155

RESUMO

The biology of how faces are built and come to differ from one another is complex. Discovering normal variants that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal and facial development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL's peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.


Assuntos
Desenvolvimento Ósseo/genética , Ossos Faciais/anatomia & histologia , Desenvolvimento Maxilofacial/genética , Alelos , Animais , Osso e Ossos/anatomia & histologia , Mapeamento Cromossômico/métodos , Camundongos de Cruzamento Colaborativo/genética , Face/anatomia & histologia , Feminino , Variação Genética/genética , Genótipo , Masculino , Camundongos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética
7.
Hum Genet ; 139(11): 1429-1441, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32488467

RESUMO

Autozygosity-driven exome analysis has been shown effective for identification of genes underlying recessive diseases especially in countries of the so-called Greater Middle East (GME), where high consanguinity unravels the phenotypic effects of recessive alleles and large family sizes facilitate homozygosity mapping. In Italy, as in most European countries, consanguinity is estimated low. Nonetheless, consanguineous Italian families are not uncommon in publications of genetic findings and are often key to new associations of genes with rare diseases. We collected 52 patients from 47 consanguineous families with suspected recessive diseases, 29 originated in GME countries and 18 of Italian descent. We performed autozygosity-driven exome analysis by detecting long runs of homozygosity (ROHs > 1.5 Mb) and by prioritizing candidate clinical variants within. We identified a pathogenic synonymous variant that had been previously missed in NARS2 and we increased an initial high diagnostic rate (47%) to 55% by matchmaking our candidate genes and including in the analysis shorter ROHs that may also happen to be autozygous. GME and Italian families contributed to diagnostic yield comparably. We found no significant difference either in the extension of the autozygous genome, or in the distribution of candidate clinical variants between GME and Italian families, while we showed that the average autozygous genome was larger and the mean number of candidate clinical variants was significantly higher (p = 0.003) in mutation-positive than in mutation-negative individuals, suggesting that these features influence the likelihood that the disease is autozygosity-related. We highlight the utility of autozygosity-driven genomic analysis also in countries and/or communities, where consanguinity is not widespread cultural tradition.


Assuntos
Testes Genéticos/métodos , Genoma Humano/genética , Mapeamento Cromossômico/métodos , Consanguinidade , Exoma/genética , Família , Feminino , Genes Recessivos/genética , Humanos , Itália , Masculino , Oriente Médio , Mutação/genética , Linhagem
8.
Mol Genet Genomics ; 295(5): 1187-1195, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32476049

RESUMO

Cowpea (Vigna unguiculate (L.) Walp.) is a worldwide important multifunctional legume crop for food grain, vegetable, fodder, and cover crop. Nevertheless, only limited research has been conducted on agronomic traits. Here, we report quantitative trait locus (QTL) analysis of the days to flowering (DTF) and plant height (PH) using a dense SNP linkage map recently developed from a recombinant inbred line (RIL) population derived from a cross between Golden Eye Cream and IT98K-476-8. The population was phenotyped for DTF and PH through field and greenhouse trials under two environments. The QTLs controlling these traits were mapped using multiple-environment combined and individual trial phenotypic data. The combined data analysis identified one major QTL (qDTF9.1) for DTF, and one major QTL (qPH9.1) and a minor QTL (qPH4.1) for PH. qDTF9.1 and qPH9.1 were adjacent to each other on Chromosome 9 and each explained 29.3% and 29.5% of the phenotypic variation (PVE), respectively. The individual trial data analysis identified a minor QTL (qDTF2.1) on Chromosome 2 for DTF and two minor QTLs (qPH4.1 and qPH4.2) on Chromosome 4 for PH, while the major QTLs, qDTF9.1 and qPH9.1, were consistently identified in all trials conducted. Epistasis analysis revealed that qDTF9.1 interacted with one locus on Chromosome 4, contributed 50% of the PVE, and qPH9.1 interacted with one locus on each of Chromosomes 4 and 6, contributing 30% and 23% of the PVE, respectively, suggesting that epistasis plays an important role in the trait performance. These results, therefore, provide a deeper understanding of the genetic architecture of plant DTF and PH, and molecular tools necessary for cloning the genes and for enhanced cowpea breeding.


Assuntos
Mapeamento Cromossômico/métodos , Locos de Características Quantitativas , Vigna/fisiologia , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Epistasia Genética , Flores/genética , Flores/crescimento & desenvolvimento , Fenótipo , Polimorfismo de Nucleotídeo Único , Vigna/anatomia & histologia , Vigna/genética
9.
Hum Genet ; 139(11): 1403-1415, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32451733

RESUMO

Clinically significant copy-number variants (CNVs) known to cause human diseases are routinely detected by chromosomal microarray analysis (CMA). Recently, genome sequencing (GS) has been introduced for CNV analysis; however, sequencing depth (determined by sequencing read-length and read-amount) is a variable parameter across different laboratories. Variating sequencing depths affect the CNV detection resolution and also make it difficult for cross-laboratory referencing or comparison. In this study, by using data from 50 samples with high read-depth GS (30×) and the reported clinically significant CNVs, we first demonstrated the optimal read-amount and the most cost-effective read-length for CNV analysis to be 15 million reads and single-end 50 bp (equivalent to a read-depth of 0.25-fold), respectively. In addition, we showed that CNVs at mosaic levels as low as 30% are readily detected, furthermore, CNVs larger than 2.5 Mb are also detectable at mosaic levels as low as 20%. Herein, by conducting a retrospective back-to-back comparison study of low-pass GS versus routine CMA for 532 prenatal, miscarriage, and postnatal cases, the overall diagnostic yield was 22.4% (119/532) for CMA and 23.1% (123/532) for low-pass GS. Thus, the overall relative improvement of the diagnostic yield by low-pass GS versus CMA was ~ 3.4% (4/119). Identification of cryptic and clinically significant CNVs among prenatal, miscarriage, and postnatal cases demonstrated that CNV detection at higher resolutions is warranted for clinical diagnosis regardless of referral indications. Overall, our study supports low-pass GS as the first-tier genetic test for molecular cytogenetic testing.


Assuntos
Análise Citogenética/métodos , Testes Genéticos/métodos , Genoma Humano/genética , Sequenciamento Completo do Genoma/métodos , Mapeamento Cromossômico/métodos , Variações do Número de Cópias de DNA/genética , Feminino , Feto , Humanos , Masculino , Gravidez , Estudos Retrospectivos
10.
BMC Genomics ; 21(Suppl 3): 243, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241258

RESUMO

BACKGROUND: The common marmoset (Callithrix jacchus) is one of the most studied primate model organisms. However, the marmoset genomes available in the public databases are highly fragmented and filled with sequence gaps, hindering research advances related to marmoset genomics and transcriptomics. RESULTS: Here we utilize single-molecule, long-read sequence data to improve and update the existing genome assembly and report a near-complete genome of the common marmoset. The assembly is of 2.79 Gb size, with a contig N50 length of 6.37 Mb and a chromosomal scaffold N50 length of 143.91 Mb, representing the most contiguous and high-quality marmoset genome up to date. Approximately 90% of the assembled genome was represented in contigs longer than 1 Mb, with approximately 104-fold improvement in contiguity over the previously published marmoset genome. More than 98% of the gaps from the previously published genomes were filled successfully, which improved the mapping rates of genomic and transcriptomic data on to the assembled genome. CONCLUSIONS: Altogether the updated, high-quality common marmoset genome assembly provide improvements at various levels over the previous versions of the marmoset genome assemblies. This will allow researchers working on primate genomics to apply the genome more efficiently for their genomic and transcriptomic sequence data.


Assuntos
Callithrix/genética , Mapeamento Cromossômico/métodos , Genoma/genética , Animais , Biologia Computacional/métodos , Mapeamento de Sequências Contíguas/métodos , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Alinhamento de Sequência
11.
Mol Cell ; 78(5): 975-985.e7, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32320643

RESUMO

DNA single-strand breaks (SSBs) are among the most common lesions in the genome, arising spontaneously and as intermediates of many DNA transactions. Nevertheless, in contrast to double-strand breaks (DSBs), their distribution in the genome has hardly been addressed in a meaningful way. We now present a technique based on genome-wide ligation of 3'-OH ends followed by sequencing (GLOE-Seq) and an associated computational pipeline designed for capturing SSBs but versatile enough to be applied to any lesion convertible into a free 3'-OH terminus. We demonstrate its applicability to mapping of Okazaki fragments without prior size selection and provide insight into the relative contributions of DNA ligase 1 and ligase 3 to Okazaki fragment maturation in human cells. In addition, our analysis reveals biases and asymmetries in the distribution of spontaneous SSBs in yeast and human chromatin, distinct from the patterns of DSBs.


Assuntos
Mapeamento Cromossômico/métodos , Replicação do DNA/genética , Análise de Sequência de DNA/métodos , Cromatina , DNA/genética , Quebras de DNA de Cadeia Simples , Dano ao DNA/genética , DNA Ligase Dependente de ATP/genética , Reparo do DNA/genética , Genoma/genética , Humanos , Nucleotídeos , Saccharomyces cerevisiae/genética
12.
Nat Genet ; 52(5): 516-524, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32284579

RESUMO

Upon assembling the first Gossypium herbaceum (A1) genome and substantially improving the existing Gossypium arboreum (A2) and Gossypium hirsutum ((AD)1) genomes, we showed that all existing A-genomes may have originated from a common ancestor, referred to here as A0, which was more phylogenetically related to A1 than A2. Further, allotetraploid formation was shown to have preceded the speciation of A1 and A2. Both A-genomes evolved independently, with no ancestor-progeny relationship. Gaussian probability density function analysis indicates that several long-terminal-repeat bursts that occurred from 5.7 million years ago to less than 0.61 million years ago contributed compellingly to A-genome size expansion, speciation and evolution. Abundant species-specific structural variations in genic regions changed the expression of many important genes, which may have led to fiber cell improvement in (AD)1. Our findings resolve existing controversial concepts surrounding A-genome origins and provide valuable genomic resources for cotton genetic improvement.


Assuntos
Genoma de Planta/genética , Gossypium/genética , Mapeamento Cromossômico/métodos , Fibra de Algodão , Diploide , Evolução Molecular , Genômica/métodos , Filogenia , Análise de Sequência de DNA/métodos
13.
PLoS One ; 15(4): e0231157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294096

RESUMO

We used three approaches to map the yellow rust resistance gene Yr7 and identify associated SNPs in wheat. First, we used a traditional QTL mapping approach using a double haploid (DH) population and mapped Yr7 to a low-recombination region of chromosome 2B. To fine map the QTL, we then used an association mapping panel. Both populations were SNP array genotyped allowing alignment of QTL and genome-wide association scans based on common segregating SNPs. Analysis of the association panel spanning the QTL interval, narrowed the interval down to a single haplotype block. Finally, we used mapping-by-sequencing of resistant and susceptible DH bulks to identify a candidate gene in the interval showing high homology to a previously suggested Yr7 candidate and to populate the Yr7 interval with a higher density of polymorphisms. We highlight the power of combining mapping-by-sequencing, delivering a complete list of gene-based segregating polymorphisms in the interval with the high recombination, low LD precision of the association mapping panel. Our mapping-by-sequencing methodology is applicable to any trait and our results validate the approach in wheat, where with a near complete reference genome sequence, we are able to define a small interval containing the causative gene.


Assuntos
Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Genoma de Planta/genética , Triticum/genética , Basidiomycota/patogenicidade , Resistência à Doença/genética , Haplótipos/genética , Haplótipos/imunologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Triticum/microbiologia
14.
PLoS One ; 15(4): e0231008, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240258

RESUMO

Cassava green mite [CGM, Mononychellus tanajoa (Bondar)] is the most destructive dry-season pest in most cassava production areas. The pest is responsible for cassava fresh root yield losses of over 80%. Deployment of CGM resistant cultivars is the most cost-effective and sustainable approach of alleviating such production losses. The purposes of this study were to validate the stability of CGM resistance genes found in previously published results, to identify new genes for CGM resistance in bi-parental mapping population and estimate the heritability of the trait. A total of 109 F1 progeny derived from a cross between CGM resistant parent, TMEB778 and a very susceptible parent, TMEB419 were evaluated under CGM hotspot areas in Nigeria for two cropping seasons. A total of 42,204 SNP markers with MAF ≥ 0.05 were used for single-marker analysis. The most significant QTL (S12_7962234) was identified on the left arm on chromosome 12 which explained high phenotypic variance and harboured significant single nucleotide polymorphism (SNP) markers conferring resistance to CGM and leaf pubescence (LP). Colocalization of the most significant SNP associated with resistance to CGM and LP on chromosome 12 is possibly an indication of a beneficial pleiotropic effect or are physically linked. These significant SNPs markers were intersected with the gene annotations and 33 unique genes were identified within SNPs at 4 - 8MB on chromosome 12. Among these genes, nine novel candidate genes namely; Manes.12077600, Manes.12G086200, Manes.12G061200, Manes.12G083100, Manes.12G082000, Manes.12G094100, Manes.12G075600, Manes.12G091400 and Manes.12G069300 highly expressed direct link to cassava green mite resistance. Pyramiding the new QTL/genes identified on chromosome 12 in this study with previously discovered loci, such on chromosome 8, will facilitate breeding varieties that are highly resistant CGM.


Assuntos
Resistência à Doença/genética , Manihot/genética , Ácaros/patogenicidade , Doenças das Plantas/genética , Locos de Características Quantitativas/genética , Animais , Cruzamento/métodos , Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Ligação Genética/genética , Marcadores Genéticos/genética , Masculino , Manihot/parasitologia , Nigéria , Fenótipo , Doenças das Plantas/parasitologia , Polimorfismo de Nucleotídeo Único/genética
15.
PLoS One ; 15(4): e0232048, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315356

RESUMO

Hypertension occurs at a higher rate in African Americans than in European Americans. Based on the assumption that causal variants are more frequently found on DNA segments inherited from the ancestral population with higher disease risk, we employed admixture mapping to identify genetic loci with excess local African ancestry associated with blood pressure. Chromosomal regions 1q21.2-21.3, 4p15.1, 19q12 and 20p13 were significantly associated with diastolic blood pressure (ß = 5.28, -7.94, -6.82 and 5.89, P-value = 6.39E-04, 2.07E-04, 6.56E-05 and 5.04E-04, respectively); 1q21.2-21.3 and 19q12 were also significantly associated with mean arterial pressure (ß = 5.86 and -6.40, P-value = 5.32E-04 and 6.37E-04, respectively). We further selected SNPs that had large allele frequency differences within these regions and tested their association with blood pressure. SNP rs4815428 was significantly associated with diastolic blood pressure after Bonferroni correction (ß = -2.42, P-value = 9.57E-04), and it partially explained the admixture mapping signal at 20p13. SNPs rs771205 (ß = -1.99, P-value = 3.37E-03), rs3126067, rs2184953 and rs58001094 (the latter three exhibit strong linkage disequilibrium, ß = -2.3, P-value = 1.4E-03) were identified to be significantly associated with mean arterial pressure, and together they fully explained the admixture signal at 1q21.2-21.3. Although no SNP at 4p15.1 showed large ancestral allele frequency differences in our dataset, we detected association at low-frequency African-specific variants that mapped predominantly to the gene PCDH7, which is most highly expressed in aorta. Our results suggest that these regions may harbor genetic variants that contribute to the different prevalence of hypertension.


Assuntos
Afro-Americanos/genética , Pressão Sanguínea/genética , Mapeamento Cromossômico/métodos , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos , Polimorfismo de Nucleotídeo Único , Idoso , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
16.
PLoS One ; 15(4): e0230820, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298285

RESUMO

The high toxicity of cadmium (Cd) and its ready uptake by plants has become a major agricultural problem. To investigate the genetic architecture and genetic regulation of Cd tolerance in barley, we conducted quantitative trait loci (QTL) analysis in the phenotypically polymorphic Oregon Wolfe Barley (OWB) mapping population, derived from a cross between Rec and Dom parental genotypes. Through evaluating the Cd tolerance of 87 available doubled haploid lines of the OWB mapping population at the seedling stage, one minor and one major QTL were detected on chromosomes 2H and 6H, respectively. For chlorosis and necrosis traits, the major QTL explained 47.24% and 38.59% of the phenotypic variance, respectively. RNA-Seq analysis of the parental seedlings under Cd treatment revealed 542 differentially expressed genes between Cd-tolerant Rec and Cd-susceptible Dom genotypes. By analyzing sequence variations in transcribed sequences of the parental genotypes, 155,654 SNPs and 1,525 InDels were identified between the two contrasting genotypes and may contribute to Cd tolerance. Finally, by integrating the data from the identified QTLs and RNA-Seq analysis, 16 Cd tolerance-related candidate genes were detected, nine of which were metal ion transporters. These results provide promising candidate genes for further gene cloning and improving Cd tolerance in barley.


Assuntos
Cádmio/toxicidade , Tolerância a Medicamentos/genética , Hordeum/efeitos dos fármacos , Hordeum/genética , Locos de Características Quantitativas/genética , Mapeamento Cromossômico/métodos , Cromossomos de Plantas/efeitos dos fármacos , Cromossomos de Plantas/genética , Haploidia , Oregon , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , RNA-Seq/métodos , Plântula/efeitos dos fármacos , Plântula/genética , Estresse Fisiológico/genética , Sequenciamento Completo do Exoma/métodos
17.
Am J Hum Genet ; 106(4): 496-512, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32220292

RESUMO

Most existing expression quantitative trait locus (eQTL) mapping studies have been focused on individuals of European ancestry and are underrepresented in other populations including populations with African ancestry. Lack of large-scale well-powered eQTL mapping studies in populations with African ancestry can both impede the dissemination of eQTL mapping results that would otherwise benefit individuals with African ancestry and hinder the comparable analysis for understanding how gene regulation is shaped through evolution. We fill this critical knowledge gap by performing a large-scale in-depth eQTL mapping study on 1,032 African Americans (AA) and 801 European Americans (EA) in the GENOA cohort. We identified a total of 354,931 eSNPs in AA and 371,309 eSNPs in EA, with 112,316 eSNPs overlapped between the two. We found that eQTL harboring genes (eGenes) are enriched in metabolic pathways and tend to have higher SNP heritability compared to non-eGenes. We found that eGenes that are common in the two populations tend to be less conserved than eGenes that are unique to one population, which are less conserved than non-eGenes. Through conditional analysis, we found that eGenes in AA tend to harbor more independent eQTLs than eGenes in EA, suggesting potentially diverse genetic architecture underlying expression variation in the two populations. Finally, the large sample sizes in GENOA allow us to construct accurate expression prediction models in both AA and EA, facilitating powerful transcriptome-wide association studies. Overall, our results represent an important step toward revealing the genetic architecture underlying expression variation in African Americans.


Assuntos
Afro-Americanos/genética , Grupo com Ancestrais do Continente Europeu/genética , Regulação da Expressão Gênica/genética , Locos de Características Quantitativas/genética , Mapeamento Cromossômico/métodos , Estudos de Coortes , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Transcriptoma/genética
18.
BMC Genomics ; 21(1): 203, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131731

RESUMO

BACKGROUND: Unravelling the genetic architecture of agronomic traits in walnut such as budbreak date and bearing habit, is crucial for climate change adaptation and yield improvement. A Genome-Wide Association Study (GWAS) using multi-locus models was conducted in a panel of 170 walnut accessions genotyped using the Axiom™ J. regia 700 K SNP array, with phenological data from 2018, 2019 and legacy data. These accessions come from the INRAE walnut germplasm collection which is the result of important prospecting work performed in many countries around the world. In parallel, an F1 progeny of 78 individuals segregating for phenology-related traits, was genotyped with the same array and phenotyped for the same traits, to construct linkage maps and perform Quantitative Trait Loci (QTLs) detection. RESULTS: Using GWAS, we found strong associations of SNPs located at the beginning of chromosome 1 with both budbreak and female flowering dates. These findings were supported by QTLs detected in the same genomic region. Highly significant associated SNPs were also detected using GWAS for heterodichogamy and lateral bearing habit, both on chromosome 11. We developed a Kompetitive Allele Specific PCR (KASP) marker for budbreak date in walnut, and validated it using plant material from the Walnut Improvement Program of the University of California, Davis, demonstrating its effectiveness for marker-assisted selection in Persian walnut. We found several candidate genes involved in flowering events in walnut, including a gene related to heterodichogamy encoding a sugar catabolism enzyme and a cell division related gene linked to female flowering date. CONCLUSIONS: This study enhances knowledge of the genetic architecture of important agronomic traits related to male and female flowering processes and lateral bearing in walnut. The new marker available for budbreak date, one of the most important traits for good fruiting, will facilitate the selection and development of new walnut cultivars suitable for specific climates.


Assuntos
Mapeamento Cromossômico/métodos , Estudo de Associação Genômica Ampla/métodos , Juglans/fisiologia , Locos de Características Quantitativas , Cromossomos de Plantas/genética , Juglans/genética , Desequilíbrio de Ligação , Fenótipo , Polimorfismo de Nucleotídeo Único , Sementes/genética
19.
PLoS Comput Biol ; 16(3): e1007653, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32218566

RESUMO

Social insect colonies exhibit colony-level phenotypes such as social immunity and task coordination, which are produced by the individual phenotypes. Mapping the genetic basis of such phenotypes requires associating the colony-level phenotype with the genotypes in the colony. In this paper, we examine alternative approaches to DNA extraction, library construction, and sequencing for genome wide association studies (GWAS) of colony-level traits using a population sample of Cataglyphis niger ants. We evaluate the accuracy of allele frequency estimation from sequencing a pool of individuals (pool-seq) from each colony using either whole-genome sequencing or reduced representation genomic sequencing. Based on empirical measurement of the experimental noise in sequenced DNA pools, we show that reduced representation pool-seq is drastically less accurate than whole-genome pool-seq. Surprisingly, normalized pooling of samples did not result in greater accuracy than un-normalized pooling. Subsequently, we evaluate the power of the alternative approaches for detecting quantitative trait loci (QTL) of colony-level traits by using simulations that account for an environmental effect on the phenotype. Our results can inform experimental designs and enable optimizing the power of GWAS depending on budget, availability of samples and research goals. We conclude that for a given budget, sequencing un-normalized pools of individuals from each colony provides optimal QTL detection power.


Assuntos
Mapeamento Cromossômico/métodos , Estudo de Associação Genômica Ampla/métodos , Metagenômica/métodos , Alelos , Animais , Formigas , Comportamento Animal/fisiologia , Frequência do Gene/genética , Genótipo , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas , Comportamento Social , Sequenciamento Completo do Genoma/métodos
20.
PLoS One ; 15(3): e0229564, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32119688

RESUMO

The introduction of high-yielding semi-dwarf varieties of wheat into cultivation has led to a "green revolution." This has required intensive research into various sources of dwarfism in wheat. However, there has been very little advancement in research on dwarfing genes in rye in comparison to wheat or barley. So far, three dominant dwarfing genes (Ddw1, Ddw3, and Ddw4) and three recessive genes (ct1, ct2, and np) have been characterized and precisely mapped in rye. There is no complete catalog of dwarfing genes available in rye. This paper presents an identification of the source of dwarfism and preliminary characterization of the new recessive gene dw9 from the BK-1 line. The gene was mapped on the long arm of the 6R chromosome and belongs to the GA-insensitive group. The initial characterization of the influence of this gene on morphological traits shows that it significantly affects the decrease of yielding trait parameters. A full evaluation can be performed after detailed breeding studies.


Assuntos
Nanismo/genética , Secale/genética , Biometria/métodos , Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Resistência à Doença/genética , Genes de Plantas/genética , Genes Recessivos/genética , Fenótipo , Melhoramento Vegetal/métodos , Doenças das Plantas/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA