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2.
Arterioscler Thromb Vasc Biol ; 39(10): 1925-1937, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31462092

RESUMO

Recent studies have led to a broader understanding of the genetic architecture of coronary artery disease and demonstrate that it largely derives from the cumulative effect of multiple common risk alleles individually of small effect size rather than rare variants with large effects on coronary artery disease risk. The tools applied include genome-wide association studies encompassing over 200 000 individuals complemented by bioinformatic approaches including imputation from whole-genome data sets, expression quantitative trait loci analyses, and interrogation of ENCODE (Encyclopedia of DNA Elements), Roadmap Epigenetic Project, and other data sets. Over 160 genome-wide significant loci associated with coronary artery disease risk have been identified using the genome-wide association studies approach, 90% of which are situated in intergenic regions. Here, I will describe, in part, our research over the last decade performed in collaboration with a series of bright trainees and an extensive number of groups and individuals around the world as it applies to our understanding of the genetic basis of this complex disease. These studies include computational approaches to better understand missing heritability and identify causal pathways, experimental approaches, and progress in understanding at the molecular level the function of the multiple risk loci identified and potential applications of these genomic data in clinical medicine and drug discovery.


Assuntos
Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Melhoria de Qualidade , Biologia Computacional , Previsões , Genética/tendências , Genômica/tendências , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética
4.
Am J Med Genet C Semin Med Genet ; 181(2): 150-154, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31037834

RESUMO

This Special Issue on Clinical Genetics in Asia highlights a collection of articles showing the growth, development, and current status of clinical genetics in Asia. In this Introduction, the Guest Editors share on the themes of this issue to provide useful insights into the rapid growth of genomics and clinical genetics in this region. The contents of this Issue cover a range of topics from the history and development of clinical genetics in Asia to studies on disorders with clinical significance or phenotype differences in the Asian populations to the status of precision medicine. The goal is to provide a glimpse of how significantly the field of genetics in Asia has developed in recent years with the aspiration that this can serve as a catalyst to increase international collaboration and cooperation in combating genetic diseases. We hope that this issue shows Asia's readiness and willingness to be a part of more international conversations about genetics in future.


Assuntos
Genética/tendências , Genômica/tendências , Animais , Ásia , Estudos Clínicos como Assunto , Humanos
6.
Cell ; 177(1): 24-25, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901542
7.
Cell ; 177(1): 26-31, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901543

RESUMO

The majority of studies of genetic association with disease have been performed in Europeans. This European bias has important implications for risk prediction of diseases across global populations. In this commentary, we justify the need to study more diverse populations using both empirical examples and theoretical reasoning.


Assuntos
Grupos de Populações Continentais/genética , Estudos de Associação Genética/métodos , Viés de Seleção , Predisposição Genética para Doença/genética , Técnicas Genéticas , Variação Genética/genética , Genética/tendências , Genética Humana/métodos , Humanos , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
9.
Nat Rev Drug Discov ; 18(4): 255-272, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30679805

RESUMO

Ongoing studies in many species seek to understand the origins, architecture and consequences of phenotypic variation under normal and dysfunctional conditions, with the aim of identifying targets for intervention that can prevent, stabilize or reverse disease. Some suggest that only humans are appropriate for studying these questions and argue that candidate drug targets identified in mouse models are largely unreliable. Here, we review the vast evidence showing that mouse models continue to make fundamental contributions to our understanding of genetic principles, pathogenic mechanisms and therapeutic modalities. We propose a virtuous cycle in which the power of observational studies and natural experiments in humans are closely integrated with the rigour of true experiments in model organisms.


Assuntos
Descoberta de Drogas/tendências , Genética/tendências , Camundongos/genética , Animais , Modelos Animais de Doenças , Genética Humana , Humanos
10.
Genome Biol Evol ; 11(1): 136-165, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30476040

RESUMO

Mutations spawn genetic variation which, in turn, fuels evolution. Hence, experimental investigations into the rate and fitness effects of spontaneous mutations are central to the study of evolution. Mutation accumulation (MA) experiments have served as a cornerstone for furthering our understanding of spontaneous mutations for four decades. In the pregenomic era, phenotypic measurements of fitness-related traits in MA lines were used to indirectly estimate key mutational parameters, such as the genomic mutation rate, new mutational variance per generation, and the average fitness effect of mutations. Rapidly emerging next-generating sequencing technology has supplanted this phenotype-dependent approach, enabling direct empirical estimates of the mutation rate and a more nuanced understanding of the relative contributions of different classes of mutations to the standing genetic variation. Whole-genome sequencing of MA lines bears immense potential to provide a unified account of the evolutionary process at multiple levels-the genetic basis of variation, and the evolutionary dynamics of mutations under the forces of selection and drift. In this review, we have attempted to synthesize key insights into the spontaneous mutation process that are rapidly emerging from the partnering of classical MA experiments with high-throughput sequencing, with particular emphasis on the spontaneous rates and molecular properties of different mutational classes in nuclear and mitochondrial genomes of diverse taxa, the contribution of mutations to the evolution of gene expression, and the rate and stability of transgenerational epigenetic modifications. Future advances in sequencing technologies will enable greater species representation to further refine our understanding of mutational parameters and their functional consequences.


Assuntos
Genética/tendências , Genoma , Acúmulo de Mutações , Taxa de Mutação , Sequenciamento Completo do Genoma , Animais , Epigênese Genética , Humanos , Transcrição Genética
11.
Genetics ; 210(4): 1139-1141, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30523164

RESUMO

The Genetics Society of America (GSA) Medal recognizes researchers who have made outstanding contributions to the field of genetics in the past 15 years. The 2018 GSA Medal has been awarded to Mariana Wolfner of Cornell University for her work on reproductive processes that occur around the time of fertilization. This includes characterization of seminal proteins in Drosophila melanogaster, which has uncovered a wealth of information about sexual conflict in evolution.


Assuntos
Distinções e Prêmios , Drosophila melanogaster/genética , Genética/história , Genética/tendências , Animais , História do Século XXI , Humanos , Proteínas de Plasma Seminal/genética , Comportamento Sexual , Sociedades Científicas
15.
Mol Biol Evol ; 35(6): 1558-1560, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800318
17.
18.
Trends Genet ; 34(6): 424-433, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29499907

RESUMO

Unbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel's Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of the meiotic products generated by a heterozygote. As their name implies, these loci gain a transmission advantage in heterozygotes by destroying otherwise viable meiotic products that do not inherit the driver. We review and classify killer meiotic drive genes across a wide spectrum of eukaryotes. We discuss how analyses of these ultra-selfish genes can lead to greater insight into the mechanisms of gametogenesis and the causes of infertility.


Assuntos
Alelos , Segregação de Cromossomos/genética , Genética/tendências , Meiose/genética , Eucariotos , Heterozigoto
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