Review

Authors: Jean Gayon

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

Review

Authors: Anna S Nam, Ronan Chaligne, Dan A Landau...

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

Authors:

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

Authors: Ray E Hershberger, Michael M Givertz, Carolyn Y Ho...

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

Authors: Nicholas H Barton

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

Authors: Kwon-Kyoo Kang, Yong-Gu Cho

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

Authors: Katarina Trebušak Podkrajšek, Primož Kotnik

In the last decade, the development of high-throughput sequencing methodologies has significantly improved the gathering of genomic information and consequent under-standing of the genetic and epigenetic background of complex and monogenetic endocrine disorders [...].

Topics: Humans; Epigenomics; Epigenesis, Genetic; Genomics; Endocrine System Diseases; High-Throughput Nucleotide Sequencing

PubMed: 37761903
DOI: 10.3390/genes14091763

Authors: Robert C Elston, Jaya M Satagopan, Shuying Sun...

Common terms used in genetics with multiple meanings are explained and the terminology used in subsequent chapters is defined. Statistical Human Genetics has existed as a discipline for over a century, and during that time the meanings of many of the terms used have evolved, largely driven by molecular discoveries, to the point that molecular and statistical geneticists often have difficulty understanding each other. It is, therefore, imperative, now that so much of molecular genetics is becoming an in silico statistical science, that we have well-defined, common terminology.

Topics: Animals; Genetics; Genetics, Medical; Humans; Plants; Terminology as Topic

PubMed: 22307690
DOI: 10.1007/978-1-61779-555-8_1

Review

Authors: Kristen S Barratt, Yichen Dai, Darla R Miller...

The 35th International Mammalian Genome Conference (IMGC) was held on July 17-20, 2022 in Vancouver, British Columbia; this conference marked the first time the International Mammalian Genome Society (IMGS) hosted a meeting in Canada. Scientists from around the world participated to share advances in genetics and genomics research across mammalian species. A diverse attendance of pre-doctoral and post-doctoral trainees, young investigators, established researchers, clinicians, bioinformaticians, and computational biologists enjoyed a rich scientific program selected from 88 abstracts in the fields of cancer, conservation genetics, developmental biology, epigenetics, human disease modeling, immunology, infectious diseases, systems genetics, translational biology, and technological advances.

Topics: Animals; Humans; Genomics; Genome; Proteomics; Epigenomics; Epigenesis, Genetic; Mammals

PubMed: 36867211
DOI: 10.1007/s00335-023-09983-2

Authors: Seth M Weinberg, Robert Cornell, Elizabeth J Leslie...

Topics: Animals; Craniofacial Abnormalities; Genetic Techniques; Genetics; Head; History, 21st Century; Humans; Mice; Models, Animal; Zebrafish

PubMed: 29927928
DOI: 10.1371/journal.pgen.1007438