The Missing Diversity in Human Genetic Studies.

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.

A Scientist and a Journalist Walk into a Bar .

Who are science journalists, and how can journalists and research scientists work together to improve science communication?

The road ahead in genetics and genomics.

In celebration of the 20th anniversary of Nature Reviews Genetics, we asked 12 leading researchers to reflect on the key challenges and opportunities faced by the field of genetics and genomics. Keeping their particular research area in mind, they take stock of the current state of play and emphasize the work that remains to be done over the next few years so that, ultimately, the benefits of genetic and genomic research can be felt by everyone.

Genetics in Drug Discovery.

Drug discovery is a complex process with high attrition rate: only about half of the compounds in advanced preclinical stages actually enter human trials. Key to these failures is our lack of understanding of human biology and the difficulties in translating our preclinical knowledge into cures. Here, we examine how genetics can be leveraged in drug discovery to understand and alter human biology.

Mouse Genetic Reference Populations: Cellular Platforms for Integrative Systems Genetics.

Interrogation of disease-relevant cellular and molecular traits exhibited by genetically diverse cell populations enables in vitro systems genetics approaches for uncovering the basic properties of cellular function and identity. Primary cells, stem cells, and organoids derived from genetically diverse mouse strains, such as Collaborative Cross and Diversity Outbred populations, offer the opportunity for parallel in vitro/in vivo screening. These panels provide genetic resolution for variant discovery and functional characterization, as well as disease modeling and in vivo validation capabilities. Here we review mouse cellular systems genetics approaches for characterizing the influence of genetic variation on signaling networks and phenotypic diversity, and we discuss approaches for data integration and cross-species validation.

Genetic Villains: Killer Meiotic Drivers.

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.

When embryology meets genetics: the definition of developmentally incompetent preimplantation embryos (DIPE)-the consensus of two Italian scientific societies.

A clear definition of developmentally incompetent preimplantation embryo (DIPE) in literature is still missing, while several scientific societies are discussing this challenging topic. From both a clinical and scientific perspective, the identification of embryos unfit for reproductive purpose is crucial. This aim should be pursued in light of all diagnostic technologies for embryo evaluation, encompassing also genetic analyses, of recent implementation in IVF. The Italian context is characterized by an unusual scenario: embryos can be discarded only if not viable and cannot be used for research purposes either. Therefore, thousands of embryos, diagnosed as affected and/or aneuploid as resulting from preimplantation genetic testing (PGT) and clinically not utilizable, are cryopreserved and stored indefinitely, with important psychological, legal, and financial implications. With the aim of updating the definition of DIPE, also on the basis of the embryo genetic status, the Italian Society of Embryology, Reproduction and Research (SIERR) and the Italian Society of Human Genetic (SIGU) reviewed the literature on this topic, found a consensus, and produced a list of relevant criteria.

2018 George Lyman Duff Memorial Lecture: Genetics and Genomics of Coronary Artery Disease: A Decade of Progress.

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.

A historical approach to hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of rare neurological disorders, characterised by their extreme heterogeneity in both their clinical manifestations and genetic origins. Although Charles-Prosper Ollivier d'Angers (1796-1845) sketched out a suggestive description in 1827, it was Heinrich Erb (1840-1921) who described the clinical picture, in 1875, for "spastic spinal paralysis". Jean-Martin Charcot (1825-1893) began teaching the disorder as a clinical entity this same year. Adolf von Strümpell (1853-1925) recognised its hereditary nature in 1880 and Maurice Lorrain (1867-1956) gained posthumous fame for adding his name to that of Strümpell and forming the eponym after his 1898 thesis, the first review covering twenty-nine affected families. He benefited from the knowledge accumulated over a dozen years on this pathology by his teacher, Fulgence Raymond (1844-1910). Here I present a history across two centuries, leading to the clinical, anatomopathological, and genetic description of hereditary spastic paraplegia which today enables a better understanding of the causative cellular dysfunctions and makes it possible to envisage effective treatment.

Development of clinical genetics in Asia.

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.

Visualization: A Mind-Machine Interface for Discovery.

Computation is critical for enabling us to process data volumes and model data complexities that are unthinkable by manual means. However, we are far from automating the sense-making process. Human knowledge and reasoning are critical for discovery. Visualization offers a powerful interface between mind and machine that should be further exploited in future genome analysis tools.

Double helix of the journal «Ð¡ytology and genetics¼: fity years later.

This survey paper contains a brief analysis of publications included in current issue of scientific journal «Cytology and Genetics¼ dedicated to its 50th anniversary. These papers reflect scientific achievements of their authors in the field of genetics and cell biology and underine the potential of these two biological disciplines, forming «double helix¼ of the journal.

Cell genetic engineering ­ transmission genetics of plants.

It has been described achievements of cell and genetic engineering that led to formation of new genetics chapter ­ transmission genetics. It has been analyzed results and showed new opportunities in the field of transgenomic somatic hybrids and cybrid obtaining, production of transgenic plants with agronomic pharmaceutical application, development of transplastomic plants, accu-mulation of recombinant proteins by using the transient expression of foreign genes in plants.

The future of Evo-Devo: the inaugural meeting of the Pan American Society for evolutionary developmental biology.

What is the future of evolutionary developmental biology? This question and more were discussed at the inaugural meeting for the Pan American Society for Evolutionary Developmental Biology, held August 5-9, 2015, in Berkeley, California, USA. More than 300 participants attended the first meeting of the new society, representing the current diversity of Evo-Devo. Speakers came from throughout the Americas, presenting work using an impressive range of study systems, techniques, and approaches. Current research draws from themes including the role of gene regulatory networks, plasticity and the role of the environment, novelty, population genetics, and regeneration, using new and emerging techniques as well as traditional tools. Multiple workshops and a discussion session covered subjects both practical and theoretical, providing an opportunity for members to discuss the current challenges and future directions for Evo-Devo. The excitement and discussion generated over the course of the meeting demonstrates the current dynamism of the field, suggesting that the future of Evo-Devo is bright indeed.