A strategic research alliance: Turner syndrome and sex differences.
Date
2019-03
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Abstract
Sex chromosome constitution varies in the human population, both between the sexes (46,XX females and 46,XY males), and within the sexes (e.g., 45,X and 46,XX females, and 47,XXY and 46,XY males). Coincident with this genetic variation are numerous phenotypic differences between males and females, and individuals with sex chromosome aneuploidy. However, the molecular mechanisms by which sex chromosome constitution impacts phenotypes at the cellular, tissue, and organismal levels remain largely unexplored. Thus, emerges a fundamental question connecting the study of sex differences and sex chromosome aneuploidy syndromes: How does sex chromosome constitution influence phenotype? Here, we focus on Turner syndrome (TS), associated with the 45,X karyotype, and its synergies with the study of sex differences. We review findings from evolutionary studies of the sex chromosomes, which identified genes that are most likely to contribute to phenotypes as a result of variation in sex chromosome constitution. We then explore strategies for investigating the direct effects of the sex chromosomes, and the evidence for specific sex chromosome genes impacting phenotypes. In sum, we argue that integrating the study of TS with sex differences offers a mutually beneficial alliance to identify contributions of the sex chromosomes to human development, health, and disease.
Type
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
San Roman, Adrianna K, David C Page and David C Page (2019). A strategic research alliance: Turner syndrome and sex differences. American journal of medical genetics. Part C, Seminars in medical genetics, 181(1). pp. 59–67. 10.1002/ajmg.c.31677 Retrieved from https://hdl.handle.net/10161/30723.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Adrianna Katrina San Roman
Biomedical research has historically ignored the role that sex differences play in health and disease, resulting in disparities in both healthcare and our understanding of the basic human biology that drives medical advancements. However, we are developing an increasing appreciation for important differences between sexes that manifest across the lifespan and in disease. Sex-biased phenotypes can be found in physical traits such as height, body fat percentage, and proportions of immune cell types. Furthermore, a wide variety of diseases have significant sex-biases. For instance, many autoimmune diseases are more prevalent in females, including lupus, which occurs in nine females for every one male. In contrast, most non-reproductive cancers, and several neurodevelopmental disorders such as autism and attention-deficit hyperactivity disorder are more common in males. The molecular mechanisms that lead to these sex differences are largely unknown despite the fact that sex chromosome constitution – the number of X and Y chromosomes – is the largest source of genetic variation in the human population. A better understanding of the molecular mechanisms by which these genetic differences, in combination with environmental and hormonal factors, result in the vast phenotypic differences seen across the spectrum of sex is critical for developing effective treatment and prevention strategies for disease and addressing historical disparities in research and clinical care.
The goal of the San Roman lab is to uncover the molecular mechanisms of sex differences in human biology. Since sex-biased traits likely have multifactorial etiologies, we leverage powerful technologies of human genetics to dissect the complex variable of sex into its fundamental building blocks. To study how sex chromosome constitution influences cellular phenotypes, we developed a unique human cell line repository from hundreds of individuals that have natural variation in the number of sex chromosomes – from one to four copies of the X chromosome and zero to four copies of the Y chromosome. Using this system, we recently showed that the number of X or Y chromosomes in a cell influences the expression of a remarkable 20% of genes across the genome and discovered key transcription factors on the sex chromosomes that underlie this regulation.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.