Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 68
Filtrar
2.
Hum Mol Genet ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415308

RESUMO

We conducted cohort- and race-specific epigenome-wide association analyses of mtDNA copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated CpG sites (p < 1 x 10-7), with a 0.7 to 3.0 standard deviation increase (3 CpGs) or decrease (18 CpGs) in mtDNA CN corresponding to a 1% increase in DNA methylation. Several significant CpGs have been reported to be associated with at least two risk factors (e.g. chronological age or smoking) for cardiovascular disease (CVD). Five genes (PRDM16, NR1H3, XRCC3, POLK, and PDSS2), which harbor nine significant CpGs, are known to be involved in mitochondrial biosynthesis and functions. For example, NR1H3 encodes a transcription factor that is differentially expressed during an adipose tissue transition. The methylation level of cg09548275 in NR1H3 was negatively associated with mtDNA CN (effect size = -1.71, p = 4 x 10-8) and positively associated with the NR1H3 expression level (effect size = 0.43, p = 0.0003), which indicates that the methylation level in NR1H3 may underlie the relationship between mtDNA CN, the NR1H3 transcription factor, and energy expenditure. In summary, the study results suggest that mtDNA CN variation in whole blood is associated with DNA methylation levels in genes that are involved in a wide range of mitochondrial activities. These findings will help reveal molecular mechanisms between mtDNA CN and CVD.

3.
Genome Biol ; 22(1): 242, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425859

RESUMO

To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify SLC6A20 and CXCR6 as putative causal genes that modulate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between correlational and causal studies of human biology.


Assuntos
COVID-19/genética , Proteínas de Membrana Transportadoras/genética , Locos de Características Quantitativas , Receptores CXCR6/genética , Cromossomos Humanos Par 3/genética , Humanos , Fenótipo
4.
PLoS Genet ; 17(7): e1009684, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34314424

RESUMO

Functional mechanisms remain unknown for most genetic loci associated to complex human traits and diseases. In this study, we first mapped trans-eQTLs in a data set of primary monocytes stimulated with LPS, and discovered that a risk variant for autoimmune disease, rs17622517 in an intron of C5ORF56, affects the expression of the transcription factor IRF1 20 kb away. The cis-regulatory effect specific to IRF1 is active under early immune stimulus, with a large number of trans-eQTL effects across the genome under late LPS response. Using CRISPRi silencing, we showed that perturbation of the SNP locus downregulates IRF1 and causes widespread transcriptional effects. Genome editing by CRISPR had suggestive recapitulation of the LPS-specific trans-eQTL signal and lent support for the rs17622517 site being functional. Our results suggest that this common genetic variant affects inter-individual response to immune stimuli via regulation of IRF1. For this autoimmune GWAS locus, our work provides evidence of the functional variant, demonstrates a condition-specific enhancer effect, identifies IRF1 as the likely causal gene in cis, and indicates that overactivation of the downstream immune-related pathway may be the cellular mechanism increasing disease risk. This work not only provides rare experimental validation of a master-regulatory trans-eQTL, but also demonstrates the power of eQTL mapping to build mechanistic hypotheses amenable for experimental follow-up using the CRISPR toolkit.

5.
Genome Med ; 13(1): 66, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883027

RESUMO

BACKGROUND: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression. METHODS: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with and without chronic obstructive pulmonary disease (COPD) and replicated these associations in two asthma cohorts, SARP and MAST. To identify airway biology beyond ACE2 binding that may contribute to increased susceptibility, we used gene set enrichment analyses to determine if gene expression changes indicative of a suppressed airway immune response observed early in SARS-CoV-2 infection are also observed in association with host factors. To identify host genetic variants affecting COVID-19 susceptibility in SPIROMICS, we performed expression quantitative trait (eQTL) mapping and investigated the phenotypic associations of the eQTL variants. RESULTS: We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. CONCLUSIONS: These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.


Assuntos
Brônquios , COVID-19/genética , Mucosa Respiratória , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/genética , Asma/genética , COVID-19/imunologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/imunologia , Expressão Gênica , Variação Genética , Humanos , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/imunologia , Doença Pulmonar Obstrutiva Crônica/genética , Locos de Características Quantitativas , Fatores de Risco , Fumar/genética
6.
Cell ; 184(10): 2633-2648.e19, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33864768

RESUMO

Long non-coding RNA (lncRNA) genes have well-established and important impacts on molecular and cellular functions. However, among the thousands of lncRNA genes, it is still a major challenge to identify the subset with disease or trait relevance. To systematically characterize these lncRNA genes, we used Genotype Tissue Expression (GTEx) project v8 genetic and multi-tissue transcriptomic data to profile the expression, genetic regulation, cellular contexts, and trait associations of 14,100 lncRNA genes across 49 tissues for 101 distinct complex genetic traits. Using these approaches, we identified 1,432 lncRNA gene-trait associations, 800 of which were not explained by stronger effects of neighboring protein-coding genes. This included associations between lncRNA quantitative trait loci and inflammatory bowel disease, type 1 and type 2 diabetes, and coronary artery disease, as well as rare variant associations to body mass index.

7.
medRxiv ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33880488

RESUMO

To date the locus with the most robust human genetic association to COVID-19 susceptibility is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify SLC6A20 and CXCR6 as putative causal genes that mediate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between correlational and causal studies of human biology.

8.
Genome Biol ; 22(1): 49, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499903

RESUMO

The resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the phenotypic consequences of transcriptome regulation and a blueprint for the functional interpretation of genome-wide association study-discovered loci. Across a broad set of complex traits and diseases, we demonstrate widespread dose-dependent effects of RNA expression and splicing. We develop a data-driven framework to benchmark methods that prioritize causal genes and find no single approach outperforms the combination of multiple approaches. Using colocalization and association approaches that take into account the observed allelic heterogeneity of gene expression, we propose potential target genes for 47% (2519 out of 5385) of the GWAS loci examined.

9.
Cell ; 184(1): 92-105.e16, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33147445

RESUMO

To better understand host-virus genetic dependencies and find potential therapeutic targets for COVID-19, we performed a genome-scale CRISPR loss-of-function screen to identify host factors required for SARS-CoV-2 viral infection of human alveolar epithelial cells. Top-ranked genes cluster into distinct pathways, including the vacuolar ATPase proton pump, Retromer, and Commander complexes. We validate these gene targets using several orthogonal methods such as CRISPR knockout, RNA interference knockdown, and small-molecule inhibitors. Using single-cell RNA-sequencing, we identify shared transcriptional changes in cholesterol biosynthesis upon loss of top-ranked genes. In addition, given the key role of the ACE2 receptor in the early stages of viral entry, we show that loss of RAB7A reduces viral entry by sequestering the ACE2 receptor inside cells. Overall, this work provides a genome-scale, quantitative resource of the impact of the loss of each host gene on fitness/response to viral infection.


Assuntos
COVID-19/genética , COVID-19/virologia , Interações Hospedeiro-Patógeno , SARS-CoV-2/fisiologia , Células A549 , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Vias Biossintéticas , COVID-19/metabolismo , Colesterol/biossíntese , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endossomos/metabolismo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes/métodos , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Interferência de RNA , SARS-CoV-2/crescimento & desenvolvimento , Análise de Célula Única , Carga Viral/efeitos dos fármacos , Proteínas rab de Ligação ao GTP/genética
10.
Genome Med ; 12(1): 79, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32912286

RESUMO

We present an assay to experimentally test the regulatory effects of genetic variants within transcripts using CRISPR/Cas9 followed by targeted sequencing. We applied the assay to 32 premature stop-gained variants across the genome and in two Mendelian disease genes, 33 putative causal variants of eQTLs, and 62 control variants in HEK293T cells, replicating a subset of variants in HeLa cells. We detected significant effects in the expected direction (in 60% of variants), demonstrating the ability of the assay to capture regulatory effects of eQTL variants and nonsense-mediated decay triggered by premature stop-gained variants. The results suggest a utility for validating transcript-level effects of genetic variants.

11.
Genome Biol ; 21(1): 233, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32912333

RESUMO

BACKGROUND: Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains individuals of European ancestry, but the v8 release also includes up to 15% of individuals of non-European ancestry. Assessing ancestry-based adjustments in GTEx improves portability of this research across populations and further characterizes the impact of population structure on GWAS colocalization. RESULTS: Here, we identify a subset of 117 individuals in GTEx (v8) with a high degree of population admixture and estimate genome-wide local ancestry. We perform genome-wide cis-eQTL mapping using admixed samples in seven tissues, adjusted by either global or local ancestry. Consistent with previous work, we observe improved power with local ancestry adjustment. At loci where the two adjustments produce different lead variants, we observe 31 loci (0.02%) where a significant colocalization is called only with one eQTL ancestry adjustment method. Notably, both adjustments produce similar numbers of significant colocalizations within each of two different colocalization methods, COLOC and FINEMAP. Finally, we identify a small subset of eQTL-associated variants highly correlated with local ancestry, providing a resource to enhance functional follow-up. CONCLUSIONS: We provide a local ancestry map for admixed individuals in the GTEx v8 release and describe the impact of ancestry and admixture on gene expression, eQTLs, and GWAS colocalization. While the majority of the results are concordant between local and global ancestry-based adjustments, we identify distinct advantages and disadvantages to each approach.


Assuntos
Grupos de Populações Continentais/genética , Genoma Humano , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Expressão Gênica , Genótipo , Humanos
12.
Genome Biol ; 21(1): 234, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32912332

RESUMO

Allele expression (AE) analysis robustly measures cis-regulatory effects. Here, we present and demonstrate the utility of a vast AE resource generated from the GTEx v8 release, containing 15,253 samples spanning 54 human tissues for a total of 431 million measurements of AE at the SNP level and 153 million measurements at the haplotype level. In addition, we develop an extension of our tool phASER that allows effect sizes of cis-regulatory variants to be estimated using haplotype-level AE data. This AE resource is the largest to date, and we are able to make haplotype-level data publicly available. We anticipate that the availability of this resource will enable future studies of regulatory variation across human tissues.


Assuntos
Alelos , Expressão Gênica , Genoma Humano , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , Análise de Sequência de RNA
13.
Science ; 369(6509)2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32913072

RESUMO

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.


Assuntos
Regulação da Expressão Gênica , Expressão Gênica , Caracteres Sexuais , Cromossomos Humanos X/genética , Doença/genética , Epigênese Genética , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Especificidade de Órgãos , Regiões Promotoras Genéticas , Locos de Características Quantitativas , Fatores Sexuais
14.
Science ; 369(6509)2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32913073

RESUMO

Rare genetic variants are abundant across the human genome, and identifying their function and phenotypic impact is a major challenge. Measuring aberrant gene expression has aided in identifying functional, large-effect rare variants (RVs). Here, we expanded detection of genetically driven transcriptome abnormalities by analyzing gene expression, allele-specific expression, and alternative splicing from multitissue RNA-sequencing data, and demonstrate that each signal informs unique classes of RVs. We developed Watershed, a probabilistic model that integrates multiple genomic and transcriptomic signals to predict variant function, validated these predictions in additional cohorts and through experimental assays, and used them to assess RVs in the UK Biobank, the Million Veterans Program, and the Jackson Heart Study. Our results link thousands of RVs to diverse molecular effects and provide evidence to associate RVs affecting the transcriptome with human traits.


Assuntos
Variação Genética , Genoma Humano , Herança Multifatorial , Transcriptoma , Humanos , Especificidade de Órgãos
15.
Science ; 369(6509)2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32913075

RESUMO

The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type-interaction QTLs for seven cell types and show that cell type-interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type-interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.


Assuntos
Regulação da Expressão Gênica , Locos de Características Quantitativas , Transcriptoma , Células/metabolismo , Humanos , Especificidade de Órgãos , RNA Longo não Codificante/genética
16.
PLoS Genet ; 15(12): e1008481, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31834882

RESUMO

Many disease risk loci identified in genome-wide association studies are present in non-coding regions of the genome. Previous studies have found enrichment of expression quantitative trait loci (eQTLs) in disease risk loci, indicating that identifying causal variants for gene expression is important for elucidating the genetic basis of not only gene expression but also complex traits. However, detecting causal variants is challenging due to complex genetic correlation among variants known as linkage disequilibrium (LD) and the presence of multiple causal variants within a locus. Although several fine-mapping approaches have been developed to overcome these challenges, they may produce large sets of putative causal variants when true causal variants are in high LD with many non-causal variants. In eQTL studies, there is an additional source of information that can be used to improve fine-mapping called allelic imbalance (AIM) that measures imbalance in gene expression on two chromosomes of a diploid organism. In this work, we develop a novel statistical method that leverages both AIM and total expression data to detect causal variants that regulate gene expression. We illustrate through simulations and application to 10 tissues of the Genotype-Tissue Expression (GTEx) dataset that our method identifies the true causal variants with higher specificity than an approach that uses only eQTL information. Across all tissues and genes, our method achieves a median reduction rate of 11% in the number of putative causal variants. We use chromatin state data from the Roadmap Epigenomics Consortium to show that the putative causal variants identified by our method are enriched for active regions of the genome, providing orthogonal support that our method identifies causal variants with increased specificity.


Assuntos
Desequilíbrio Alélico , Cromatina/genética , Mapeamento Cromossômico/métodos , Locos de Características Quantitativas , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Herança Multifatorial , Polimorfismo de Nucleotídeo Único
17.
Science ; 366(6463): 351-356, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31601707

RESUMO

Transcriptome data can facilitate the interpretation of the effects of rare genetic variants. Here, we introduce ANEVA (analysis of expression variation) to quantify genetic variation in gene dosage from allelic expression (AE) data in a population. Application of ANEVA to the Genotype-Tissues Expression (GTEx) data showed that this variance estimate is robust and correlated with selective constraint in a gene. Using these variance estimates in a dosage outlier test (ANEVA-DOT) applied to AE data from 70 Mendelian muscular disease patients showed accuracy in detecting genes with pathogenic variants in previously resolved cases and led to one confirmed and several potential new diagnoses. Using our reference estimates from GTEx data, ANEVA-DOT can be incorporated in rare disease diagnostic pipelines to use RNA-sequencing data more effectively.


Assuntos
Variação Genética , Doenças Musculares/genética , Distrofias Musculares/genética , Doenças Raras/genética , Transcriptoma , Dosagem de Genes , Regulação da Expressão Gênica , Genoma Humano , Humanos , Modelos Genéticos , Modelos Estatísticos , Locos de Características Quantitativas
18.
Cell ; 177(1): 70-84, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901550

RESUMO

Affordable genome sequencing technologies promise to revolutionize the field of human genetics by enabling comprehensive studies that interrogate all classes of genome variation, genome-wide, across the entire allele frequency spectrum. Ongoing projects worldwide are sequencing many thousands-and soon millions-of human genomes as part of various gene mapping studies, biobanking efforts, and clinical programs. However, while genome sequencing data production has become routine, genome analysis and interpretation remain challenging endeavors with many limitations and caveats. Here, we review the current state of technologies for genetic variant discovery, genotyping, and functional interpretation and discuss the prospects for future advances. We focus on germline variants discovered by whole-genome sequencing, genome-wide functional genomic approaches for predicting and measuring variant functional effects, and implications for studies of common and rare human disease.


Assuntos
Variação Genética/genética , Genoma Humano/genética , Análise de Sequência de DNA/tendências , Bancos de Espécimes Biológicos , Mapeamento Cromossômico/métodos , Predisposição Genética para Doença/genética , Testes Genéticos/tendências , Estudo de Associação Genômica Ampla , Genômica/métodos , Genômica/tendências , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Projeto Genoma Humano , Humanos , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA/métodos , Sequenciamento Completo do Genoma/métodos , Sequenciamento Completo do Genoma/tendências
19.
Nat Genet ; 50(9): 1327-1334, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30127527

RESUMO

Coding variants represent many of the strongest associations between genotype and phenotype; however, they exhibit inter-individual differences in effect, termed 'variable penetrance'. Here, we study how cis-regulatory variation modifies the penetrance of coding variants. Using functional genomic and genetic data from the Genotype-Tissue Expression Project (GTEx), we observed that in the general population, purifying selection has depleted haplotype combinations predicted to increase pathogenic coding variant penetrance. Conversely, in cancer and autism patients, we observed an enrichment of penetrance increasing haplotype configurations for pathogenic variants in disease-implicated genes, providing evidence that regulatory haplotype configuration of coding variants affects disease risk. Finally, we experimentally validated this model by editing a Mendelian single-nucleotide polymorphism (SNP) using CRISPR/Cas9 on distinct expression haplotypes with the transcriptome as a phenotypic readout. Our results demonstrate that joint regulatory and coding variant effects are an important part of the genetic architecture of human traits and contribute to modified penetrance of disease-causing variants.


Assuntos
Doença/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Sistemas CRISPR-Cas , Genoma Humano , Haplótipos , Humanos , Fenótipo , Locos de Características Quantitativas , Transcriptoma
20.
Am J Hum Genet ; 103(2): 171-187, 2018 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-30032986

RESUMO

Premature termination codon (PTC)-bearing transcripts are often degraded by nonsense-mediated decay (NMD) resulting in loss-of-function (LoF) alleles. However, not all PTCs result in LoF mutations, i.e., some such transcripts escape NMD and are translated to truncated peptide products that result in disease due to gain-of-function (GoF) effects. Since the location of the PTC is a major factor determining transcript fate, we hypothesized that depletion of protein-truncating variants (PTVs) within the gene region predicted to escape NMD in control databases could provide a rank for genic susceptibility for disease through GoF versus LoF. We developed an NMD escape intolerance score to rank genes based on the depletion of PTVs that would render them able to escape NMD using the Atherosclerosis Risk in Communities Study (ARIC) and the Exome Aggregation Consortium (ExAC) control databases, which was further used to screen the Baylor-Center for Mendelian Genomics disease database. This analysis revealed 1,996 genes significantly depleted for PTVs that are predicted to escape from NMD, i.e., PTVesc; further studies provided evidence that revealed a subset as candidate genes underlying Mendelian phenotypes. Importantly, these genes have characteristically low pLI scores, which can cause them to be overlooked as candidates for dominant diseases. Collectively, we demonstrate that this NMD escape intolerance score is an effective and efficient tool for gene discovery in Mendelian diseases due to production of truncated or altered proteins. More importantly, we provide a complementary analytical tool to aid identification of genes associated with dominant traits through a mechanism distinct from LoF.


Assuntos
Mutação com Ganho de Função/genética , Mutação/genética , Alelos , Códon sem Sentido/genética , Bases de Dados Genéticas , Exoma/genética , Humanos , Degradação do RNAm Mediada por Códon sem Sentido/genética , Fenótipo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...