-
Nature Reviews. Genetics Jan 2021Cancer represents an evolutionary process through which growing malignant populations genetically diversify, leading to tumour progression, relapse and resistance to... (Review)
Review
Cancer represents an evolutionary process through which growing malignant populations genetically diversify, leading to tumour progression, relapse and resistance to therapy. In addition to genetic diversity, the cell-to-cell variation that fuels evolutionary selection also manifests in cellular states, epigenetic profiles, spatial distributions and interactions with the microenvironment. Therefore, the study of cancer requires the integration of multiple heritable dimensions at the resolution of the single cell - the atomic unit of somatic evolution. In this Review, we discuss emerging analytic and experimental technologies for single-cell multi-omics that enable the capture and integration of multiple data modalities to inform the study of cancer evolution. These data show that cancer results from a complex interplay between genetic and non-genetic determinants of somatic evolution.
Topics: Clonal Evolution; Computational Biology; Epigenomics; Genetic Variation; Genomics; Humans; Mutation; Neoplasms; Single-Cell Analysis; Tumor Microenvironment
PubMed: 32807900
DOI: 10.1038/s41576-020-0265-5 -
Comptes Rendus Biologies 2016The origins of genetics are to be found in Gregor Mendel's memoir on plant hybridization (1865). However, the word 'genetics' was only coined in 1906, to designate the... (Review)
Review
The origins of genetics are to be found in Gregor Mendel's memoir on plant hybridization (1865). However, the word 'genetics' was only coined in 1906, to designate the new science of heredity. Founded upon the Mendelian method for analyzing the products of crosses, this science is distinguished by its explicit purpose of being a general 'science of heredity', and by the introduction of totally new biological concepts (in particular those of gene, genotype, and phenotype). In the 1910s, Mendelian genetics fused with the chromosomal theory of inheritance, giving rise to what is still called 'classical genetics'. Within this framework, the gene is simultaneously a unit of function and transmission, a unit of recombination, and of mutation. Until the early 1950s, these concepts of the gene coincided. But when DNA was found to be the material basis of inheritance, this congruence dissolved. Then began the venture of molecular biology, which has never stopped revealing the complexity of the way in which hereditary material functions.
Topics: Animals; Epigenomics; Genes; Genetics; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Molecular Biology; Plants
PubMed: 27263362
DOI: 10.1016/j.crvi.2016.05.009 -
Genes Dec 2022In the past 20 years, plant genetics and breeding research using molecular biology has been greatly improved via the functional analysis of genes, species identification...
In the past 20 years, plant genetics and breeding research using molecular biology has been greatly improved via the functional analysis of genes, species identification and transformation techniques [...].
Topics: Plant Breeding; Plants; Genetic Research; Molecular Biology
PubMed: 36672792
DOI: 10.3390/genes14010051 -
Nucleic Acids Research Jan 2021Organismal aging is driven by interconnected molecular changes encompassing internal and extracellular factors. Combinational analysis of high-throughput 'multi-omics'...
Organismal aging is driven by interconnected molecular changes encompassing internal and extracellular factors. Combinational analysis of high-throughput 'multi-omics' datasets (gathering information from genomics, epigenomics, transcriptomics, proteomics, metabolomics and pharmacogenomics), at either populational or single-cell levels, can provide a multi-dimensional, integrated profile of the heterogeneous aging process with unprecedented throughput and detail. These new strategies allow for the exploration of the molecular profile and regulatory status of gene expression during aging, and in turn, facilitate the development of new aging interventions. With a continually growing volume of valuable aging-related data, it is necessary to establish an open and integrated database to support a wide spectrum of aging research. The Aging Atlas database aims to provide a wide range of life science researchers with valuable resources that allow access to a large-scale of gene expression and regulation datasets created by various high-throughput omics technologies. The current implementation includes five modules: transcriptomics (RNA-seq), single-cell transcriptomics (scRNA-seq), epigenomics (ChIP-seq), proteomics (protein-protein interaction), and pharmacogenomics (geroprotective compounds). Aging Atlas provides user-friendly functionalities to explore age-related changes in gene expression, as well as raw data download services. Aging Atlas is freely available at https://bigd.big.ac.cn/aging/index.
Topics: Aging; Databases, Genetic; Epigenomics; Genomics; Humans; Pharmacogenetics; Transcriptome
PubMed: 33119753
DOI: 10.1093/nar/gkaa894 -
Genetics in Medicine : Official Journal... Sep 2018The purpose of this document is to provide updated guidance for the genetic evaluation of cardiomyopathy and for an approach to manage secondary findings from...
PURPOSE
The purpose of this document is to provide updated guidance for the genetic evaluation of cardiomyopathy and for an approach to manage secondary findings from cardiomyopathy genes. The genetic bases of the primary cardiomyopathies (dilated, hypertrophic, arrhythmogenic right ventricular, and restrictive) have been established, and each is medically actionable; in most cases established treatments or interventions are available to improve survival, reduce morbidity, and enhance quality of life.
METHODS
A writing group of cardiologists and genetics professionals updated guidance, first published in 2009 for the Heart Failure Society of America (HFSA), in a collaboration with the American College of Medical Genetics and Genomics (ACMG). Each recommendation was assigned to teams of individuals by expertise, literature was reviewed, and recommendations were decided by consensus of the writing group. Recommendations for family history, phenotype screening of at-risk family members, referral to expert centers as needed, genetic counseling, and cardiovascular therapies, informed in part by phenotype, are presented in the HFSA document.
RESULTS
A genetic evaluation of cardiomyopathy is indicated with a cardiomyopathy diagnosis, which includes genetic testing. Guidance is also provided for clinical approaches to secondary findings from cardiomyopathy genes. This is relevant as cardiomyopathy is the phenotype associated with 27% of the genes on the ACMG list for return of secondary findings. Recommendations herein are considered expert opinion per current ACMG policy as no systematic approach to literature review was conducted.
CONCLUSION
Genetic testing is indicated for cardiomyopathy to assist in patient care and management of at-risk family members.
Topics: Cardiomyopathies; Genetic Counseling; Genetic Testing; Genetics; Genetics, Medical; Genomics; Genotype; Humans; Incidental Findings; Mass Screening; Phenotype; Quality of Life; United States
PubMed: 29904160
DOI: 10.1038/s41436-018-0039-z -
PLoS Biology Jul 2022A new collection of articles celebrating the bicentennial of Gregor Mendel's birth discuss his life, work and legacy in modern-day genetic research.
A new collection of articles celebrating the bicentennial of Gregor Mendel's birth discuss his life, work and legacy in modern-day genetic research.
Topics: Genetic Research; Genetics; History, 19th Century
PubMed: 35901028
DOI: 10.1371/journal.pbio.3001760 -
Proceedings of the National Academy of... Jul 2022When Mendel's work was rediscovered in 1900, and extended to establish classical genetics, it was initially seen in opposition to Darwin's theory of evolution by natural...
When Mendel's work was rediscovered in 1900, and extended to establish classical genetics, it was initially seen in opposition to Darwin's theory of evolution by natural selection on continuous variation, as represented by the biometric research program that was the foundation of quantitative genetics. As Fisher, Haldane, and Wright established a century ago, Mendelian inheritance is exactly what is needed for natural selection to work efficiently. Yet, the synthesis remains unfinished. We do not understand why sexual reproduction and a fair meiosis predominate in eukaryotes, or how far these are responsible for their diversity and complexity. Moreover, although quantitative geneticists have long known that adaptive variation is highly polygenic, and that this is essential for efficient selection, this is only now becoming appreciated by molecular biologists-and we still do not have a good framework for understanding polygenic variation or diffuse function.
Topics: Biological Evolution; Genetics; Heredity; History, 19th Century; Selection, Genetic
PubMed: 35858408
DOI: 10.1073/pnas.2122147119 -
Circulation Research Jul 2010
Topics: Cardiovascular Diseases; Genetics, Medical; Genome, Human; Humans; Periodicals as Topic; Pharmacogenetics
PubMed: 20616334
DOI: 10.1161/CIRCRESAHA.110.226258 -
American Journal of Medical Genetics.... Sep 2017Large-scale consortia including the Psychiatric Genomics Consortium, the Common Minds Consortium, BrainSeq and PsychENCODE, and many other studies taken together provide... (Review)
Review
Large-scale consortia including the Psychiatric Genomics Consortium, the Common Minds Consortium, BrainSeq and PsychENCODE, and many other studies taken together provide increasingly detailed insights into the genetic and epigenetic risk architectures of schizophrenia (SCZ) and offer vast amounts of molecular information, but with largely unexplored therapeutic potential. Here we discuss how epigenomic studies in human brain could guide animal work to test the impact of disease-associated alterations in chromatin structure and function on cognition and behavior. For example, transcription factors such as MYOCYTE-SPECIFIC ENHANCER FACTOR 2C (MEF2C), or multiple regulators of the open chromatin mark, methyl-histone H3-lysine 4, are associated with the genetic risk architectures of common psychiatric disease and alterations in chromatin structure and function in diseased brain tissue. Importantly, these molecules also affect cognition and behavior in genetically engineered mice, including virus-mediated expression changes in prefrontal cortex (PFC) and other key nodes in the circuitry underlying psychosis. Therefore, preclinical and small laboratory animal work could target genomic sequences affected by chromatin alterations in SCZ. To this end, in vivo editing of enhancer and other regulatory non-coding DNA by RNA-guided nucleases including CRISPR-Cas, and designer transcription factors, could be expected to deliver pipelines for novel therapeutic approaches aimed at improving cognitive dysfunction and other core symptoms of SCZ.
Topics: Animals; Epigenomics; Mice; Schizophrenia
PubMed: 28699694
DOI: 10.1002/ajmg.b.32566 -
Genes Jan 2022True truffle ( spp.) is one group of ascomycetes with great economic importance. During the last 30 years, numerous fine-scale population genetics studies were conducted... (Review)
Review
True truffle ( spp.) is one group of ascomycetes with great economic importance. During the last 30 years, numerous fine-scale population genetics studies were conducted on different truffle species, aiming to answer several key questions regarding their life cycles; these questions are important for their cultivation. It is now evident that truffles are heterothallic, but with a prevalent haploid lifestyle. Strains forming ectomycorrhizas and germinating ascospores act as maternal and paternal partners respectively. At the same time, a number of large-scale studies were carried out, highlighting the influences of the last glaciation and river isolations on the genetic structure of truffles. A retreat to southern refugia during glaciation, and a northward expansion post glaciation, were revealed in all studied European truffles. The Mediterranean Sea, acting as a barrier, has led to the existence of several refugia in different peninsulas for a single species. Similarly, large rivers in southwestern China act as physical barriers to gene flow for truffles in this region. Further studies can pay special attention to population genetics of species with a wide distribution range, such as , and the correlation between truffle genetic structure and the community composition of truffle-associated bacteria.
Topics: Ascomycota; Genetics, Population; Life Cycle Stages; Phylogeography; Species Specificity
PubMed: 35052485
DOI: 10.3390/genes13010145