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2.
Science ; 373(6562): 1458-1459, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34554809
4.
Curr Biol ; 31(16): 3504-3514.e9, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34171302

RESUMO

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has emphasized the vulnerability of human populations to novel viral pressures, despite the vast array of epidemiological and biomedical tools now available. Notably, modern human genomes contain evolutionary information tracing back tens of thousands of years, which may help identify the viruses that have impacted our ancestors-pointing to which viruses have future pandemic potential. Here, we apply evolutionary analyses to human genomic datasets to recover selection events involving tens of human genes that interact with coronaviruses, including SARS-CoV-2, that likely started more than 20,000 years ago. These adaptive events were limited to the population ancestral to East Asian populations. Multiple lines of functional evidence support an ancient viral selective pressure, and East Asia is the geographical origin of several modern coronavirus epidemics. An arms race with an ancient coronavirus, or with a different virus that happened to use similar interactions as coronaviruses with human hosts, may thus have taken place in ancestral East Asian populations. By learning more about our ancient viral foes, our study highlights the promise of evolutionary information to better predict the pandemics of the future. Importantly, adaptation to ancient viral epidemics in specific human populations does not necessarily imply any difference in genetic susceptibility between different human populations, and the current evidence points toward an overwhelming impact of socioeconomic factors in the case of coronavirus disease 2019 (COVID-19).


Assuntos
Infecções por Coronavirus/história , Coronavirus/genética , Genoma Humano/genética , Interações entre Hospedeiro e Microrganismos/genética , Pandemias/história , Infecções por Coronavirus/virologia , Conjuntos de Dados como Assunto , Evolução Molecular , Extremo Oriente/epidemiologia , Frequência do Gene , Predisposição Genética para Doença , Genoma Viral/genética , Estudo de Associação Genômica Ampla , História Antiga , Projeto Genoma Humano , Humanos , Mutação , Filogenia , Seleção Genética
5.
Brief Bioinform ; 22(5)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-33822888

RESUMO

Next-generation sequencing studies are dependent on a high-quality reference genome for single nucleotide variant (SNV) calling. Although the two most recent builds of the human genome are widely used, position information is typically not directly comparable between them. Re-alignment gives the most accurate position information, but this procedure is often computationally expensive, and therefore, tools such as liftOver and CrossMap are used to convert data from one build to another. However, the positions of converted SNVs do not always match SNVs derived from aligned data, and in some instances, SNVs are known to change chromosome when converted. This is a significant problem when compiling sequencing resources or comparing results across studies. Here, we describe a novel algorithm to identify positions that are unstable when converting between human genome reference builds. These positions are detected independent of the conversion tools and are determined by the chain files, which provide a mapping of contiguous positions from one build to another. We also provide the list of unstable positions for converting between the two most commonly used builds GRCh37 and GRCh38. Pre-excluding SNVs at these positions, prior to conversion, results in SNVs that are stable to conversion. This simple procedure gives the same final list of stable SNVs as applying the algorithm and subsequently removing variants at unstable positions. This work highlights the care that must be taken when converting SNVs between genome builds and provides a simple method for ensuring higher confidence converted data. Unstable positions and algorithm code, available at https://github.com/cathaloruaidh/genomeBuildConversion.


Assuntos
Algoritmos , Conversão Gênica , Genoma Humano , Polimorfismo de Nucleotídeo Único , Navegador , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Projeto Genoma Humano , Humanos , Sequenciamento Completo do Genoma/métodos
6.
Trends Genet ; 37(7): 625-630, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33879355

RESUMO

Comprehensively characterizing the cellular composition and organization of tissues has been a long-term scientific challenge that has limited our ability to study fundamental and clinical aspects of human physiology. The Human Cell Atlas (HCA) is a global collaborative effort to create a reference map of all human cells as a basis for both understanding human health and diagnosing, monitoring, and treating disease. Many aspects of the HCA are analogous to the Human Genome Project (HGP), whose completion presents a major milestone in modern biology. To commemorate the HGP's 20-year anniversary of completion, we discuss the launch of the HCA in light of the HGP, and highlight recent progress by the HCA consortium.


Assuntos
Linhagem da Célula/genética , Fenômenos Fisiológicos Celulares/genética , Células/classificação , Genoma Humano/genética , Projeto Genoma Humano , Humanos
7.
Nat Commun ; 12(1): 1424, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658504

RESUMO

Genetic studies of the transcriptome help bridge the gap between genetic variation and phenotypes. To maximize the potential of such studies, efficient methods to identify expression quantitative trait loci (eQTLs) and perform fine-mapping and genetic prediction of gene expression traits are needed. Current methods that leverage both total read counts and allele-specific expression to identify eQTLs are generally computationally intractable for large transcriptomic studies. Here, we describe a unified framework that addresses these needs and is scalable to thousands of samples. Using simulations and data from GTEx, we demonstrate its calibration and performance. For example, mixQTL shows a power gain equivalent to a 29% increase in sample size for genes with sufficient allele-specific read coverage. To showcase the potential of mixQTL, we apply it to 49 GTEx tissues and find 20% additional eQTLs (FDR < 0.05, per tissue) that are significantly more enriched among trait associated variants and candidate cis-regulatory elements comparing to the standard approach.


Assuntos
Alelos , Mapeamento Cromossômico/métodos , Locos de Características Quantitativas , Bases de Dados Genéticas , Estudo de Associação Genômica Ampla , Projeto Genoma Humano , Humanos , Modelos Genéticos , Modelos Estatísticos , Sequências Reguladoras de Ácido Nucleico
8.
Hum Genomics ; 15(1): 12, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568209

RESUMO

This letter is the Human Genome Organisation's summary reaction to the 2020 COVID-19 pandemic. It identifies key areas for genomics research, and areas in which genomic scientists can contribute to a global response to the pandemic. The letter has been reviewed and endorsed by the HUGO Committee on Ethics, Law and Society (CELS) and the HUGO Council.


Assuntos
COVID-19 , SARS-CoV-2/genética , Sociedades Científicas , COVID-19/epidemiologia , Genômica/organização & administração , Projeto Genoma Humano , Humanos , Disseminação de Informação , Organizações sem Fins Lucrativos , Pandemias
12.
Science ; 371(6529): 545, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33542112
16.
Sci Rep ; 11(1): 449, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432083

RESUMO

The ribosomal RNA genes (rDNA) are tandemly arrayed in most eukaryotes and exhibit vast copy number variation. There is growing interest in integrating this variation into genotype-phenotype associations. Here, we explored a possible association of rDNA copy number variation with autism spectrum disorder and found no difference between probands and unaffected siblings. Because short-read sequencing estimates of rDNA copy number are error prone, we sought to validate our 45S estimates. Previous studies reported tightly correlated, concerted copy number variation between the 45S and 5S arrays, which should enable the validation of 45S copy number estimates with pulsed-field gel-verified 5S copy numbers. Here, we show that the previously reported strong concerted copy number variation may be an artifact of variable data quality in the earlier published 1000 Genomes Project sequences. We failed to detect a meaningful correlation between 45S and 5S copy numbers in thousands of samples from the high-coverage Simons Simplex Collection dataset as well as in the recent high-coverage 1000 Genomes Project sequences. Our findings illustrate the challenge of genotyping repetitive DNA regions accurately and call into question the accuracy of recently published studies of rDNA copy number variation in cancer that relied on diverse publicly available resources for sequence data.


Assuntos
Variações do Número de Cópias de DNA/genética , DNA/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Ribossômico 5S/genética , RNA Ribossômico/genética , Transtorno do Espectro Autista/genética , Confiabilidade dos Dados , Conjuntos de Dados como Assunto , Técnicas de Genotipagem , Projeto Genoma Humano , Humanos , Neoplasias/genética , Sequências Repetitivas de Ácido Nucleico/genética , Análise de Sequência de DNA
18.
Leg Med (Tokyo) ; 49: 101849, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33485062

RESUMO

In some cases, it is necessary to estimate the national origin of an unknown subject in forensic medicine. The use of single nucleotide polymorphism (SNP) markers appears to be very effective for this purpose, since genome-wide SNP genotype data of many human populations are publicly available. In this study, we examined the number of SNPs that could objectively and accurately distinguish Japanese subjects (1KG-JPT) from the other East Asians (1KG-CDX, -CHB, -CHS, and -KHV) using the combination of principal component analysis and hierarchical cluster analysis. A computer simulation showed that approximately 3000 randomly selected SNPs were enough for the discrimination. Our results suggest that at least a 0.024% coverage is needed in the next generation sequencing experiment to objectively determine whether an unknown person is Japanese or not if the amount of DNA sample from him/her is insufficient or the quality is low.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Genética Forense/métodos , Genética Populacional/métodos , Polimorfismo de Nucleotídeo Único/genética , Análise por Conglomerados , Simulação por Computador , Bases de Dados Genéticas , Extremo Oriente , Feminino , Projeto Genoma Humano , Humanos , Japão , Masculino , Análise de Componente Principal/métodos
19.
Nucleic Acids Res ; 49(D1): D1225-D1232, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33095885

RESUMO

With the advent of next-generation sequencing, large-scale initiatives for mining whole genomes and exomes have been employed to better understand global or population-level genetic architecture. India encompasses more than 17% of the world population with extensive genetic diversity, but is under-represented in the global sequencing datasets. This gave us the impetus to perform and analyze the whole genome sequencing of 1029 healthy Indian individuals under the pilot phase of the 'IndiGen' program. We generated a compendium of 55,898,122 single allelic genetic variants from geographically distinct Indian genomes and calculated the allele frequency, allele count, allele number, along with the number of heterozygous or homozygous individuals. In the present study, these variants were systematically annotated using publicly available population databases and can be accessed through a browsable online database named as 'IndiGenomes' http://clingen.igib.res.in/indigen/. The IndiGenomes database will help clinicians and researchers in exploring the genetic component underlying medical conditions. Till date, this is the most comprehensive genetic variant resource for the Indian population and is made freely available for academic utility. The resource has also been accessed extensively by the worldwide community since it's launch.


Assuntos
Bases de Dados Genéticas , Variação Genética , Genoma Humano , Projeto Genoma Humano , Software , Adulto , Exoma , Feminino , Genética Populacional/estatística & dados numéricos , Humanos , Índia , Internet , Masculino , Anotação de Sequência Molecular , Sequenciamento Completo do Genoma
20.
J Hum Genet ; 66(1): 85-91, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33057159

RESUMO

Uniform manifold approximation and projection (UMAP) has been rapidly adopted by the population genetics community to study population structure. It has become common in visualizing the ancestral composition of human genetic datasets, as well as searching for unique clusters of data, and for identifying geographic patterns. Here we give an overview of applications of UMAP in population genetics, provide recommendations for best practices, and offer insights on optimal uses for the technique.


Assuntos
Biologia Computacional/métodos , Variação Genética , Genética Populacional/métodos , Genoma Humano/genética , Genômica/métodos , Frequência do Gene , Genótipo , Antígenos HLA/genética , Projeto Genoma Humano , Humanos
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