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The genetics of being human

The genetics of being human

Editorial Special Issue: Human Genetics The genetics of being human Rhiannon Macrae Editor, Trends in Genetics ‘Nature and human life are as variou...

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Special Issue: Human Genetics

The genetics of being human Rhiannon Macrae Editor, Trends in Genetics

‘Nature and human life are as various as our several constitutions. Who shall say what prospect life offers to another?’ Henry David Thoreau As the pace of human genetic discoveries accelerates and technology becomes more sophisticated, science is beginning to reexamine the age-old philosophical question: what does it mean to be human? In this special issue of Trends in Genetics, various aspects of this question are considered, ranging from the historical to the medical and even to the political. This collection of articles reflects the rich variety of current topics in human genetics research and highlights both the progress toward and challenges ahead of a molecular understanding of our species. One of the emerging themes in human genetics is a deeper appreciation for the vast heterogeneity that exists among individuals. Three pieces in this special issue address this variation from different angles. First, William Klitz examines the major histocompatibility locus and argues not only that the number of alleles at this locus in the population is enormous, but also that the alleles themselves are short lived. This pool of quickly changing alleles serves as a reservoir for defense against pathogens, but it also has implications for the search for matching donors for stem cell transplants. Eileen Dolan and colleagues examine variation and medicine on a wider scale, discussing patient response to drug treatments and how to translate findings from genome-wide association studies (GWAS) about gene– drug interactions into clinical practice. Stepping back in time, Ron Pinhasi and colleagues provide clues about how such heterogeneity arose. They discuss recent archaeogenetics findings that are reshaping ideas about the genetic history of Europeans. Once believed to be relatively homogenous, new evidence reveals significant genetic diversity in modern European populations, which arose through the effects of environmental and cultural changes. Epigenetics is adding another layer of complexity to interindividual variation, and DNA methylation in particular is proving to be a critical factor in many cellular

processes and diseases, although its role is not always well understood. Agustin Fernandez, Covadonga Huidobro, and Mario Fraga tackle this problem head on in the case of DNA methyltransferases and cancer, arguing that they can be both tumor suppressors and oncogenes depending on the tumor stage. A piece by Carlos Lo´pez-Larrea and colleagues describes the patterns of DNA methylation in hematopoietic cells and how these patterns dynamically change during cellular differentiation in the immune system, focusing on potential therapeutic targets for immunerelated diseases. Looking more mechanistically at the role of chromatin, You-Ying Chau and Nicholas Hastie shine new light on the function of the Wilm’s Tumor protein, WT1, which has distinct and opposite roles in different tissues. They describe how WT1 switches the chromatin state of target promoters from active to repressed or vice versa, depending on the cofactor present to drive specification of either the kidney or the heart. Lastly, we include a piece by Rose McDermott and Peter Hatemi on genopolitics, a subject at the frontier of human genetics. They present a passionate case for why there is a need to understand the influence of genetics on political behaviors and discuss approaches for gaining insight into this important issue. In addition, they argue against the notion that there will be a ‘liberal gene’ or any other single gene responsible for political attitude and emphasize instead the complex interplay between genes and environment, stressing that we are not born with affiliations, but that we develop them as a result of our DNA and our experiences. Although these articles represent only a small number of the exciting advances in human genetics, they certainly demonstrate that Thoreau was right: we are a varied people, down to our DNA. We hope these pieces provide a sense of the breadth and depth to which this field is reaching, and we look forward to covering more topics in this area in future issues. We thank all the authors and reviewers for their contributions to this issue, and we thank you for reading. Your comments and ideas are always welcome, and you can contact us with feedback or questions at [email protected]

Corresponding author: Macrae, R. ([email protected]). 0168-9525/$ – see front matter ß 2012 Elsevier Ltd. All rights reserved. Trends in Genetics, October 2012, Vol. 28, No. 10