MAY 13, 2015 3:00 PM PDT

Population genomics of sex chromosome evolution

Speaker
  • Assistant Professor, School of Life Sciences, Arizona State University
    Biography
      Dr. Wilson Sayres is actively working to understand the evolution of sex chromosomes (X and Y in mammals), and also interested in using the unique properties of these chromosomes (e.g., that they spend different amounts of time in the male and female germlines, and are subject to different selective pressures) to address how mutations accumulate. To address the first area of interest, she is cataloging and interpreting variation among Y chromosomes from populations around the world. She is also comparing diversity on the sex chromosomes and non-sex chromosomes across hundreds of individuals to determine how population demography, selection, and sex-specific mutation processes combine to contribute to the accumulation of mutations in the human genome.
      <br />

    Abstract

    There is tremendous sexual dimorphism in human genetic disease susceptibility, progression, and drug response. It is thus alarming that most genome-wide association studies exclude the most sexually dimorphic regions of our genome, the sex chromosomes. An essential component of incorporating the X and Y into studies of human disease, with their unique inheritance patterns, and response to population history and selection, is to understand their evolutionary history. Ancestrally, both the X and Y chromosomes shared identical gene content, but throughout our evolutionary history the Y chromosome has lost over 90% of the gene content it once shared with the X. The loss of Y-linked sequence not only affects the fate of the Y chromosome, but it also modulates the evolution and expression of X-linked genes. XX humans inactivate gene expression on one of their X chromosomes, but not completely; 15% of genes escape X-inactivation, while another 10% escape X-inactivation in only a subset of individuals. Analyzing patterns of heterogeneous X-inactivation across individual cell lines, we show that genes on the X chromosome are silenced in response to gene loss on the Y. Variation in these patterns of silencing are important for understanding the etiology of, and variation in, X-linked diseases. Learning Objectives: 1. Explain the importance of including the human X and Y chromosomes in clinical and genetic analysis. 2. Appreciate the role of the sex chromosomes in human health and disease 3. Discuss the implications of human Y chromosome variation.


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