Recurrent structural variation, clustered sites of selection, and disease risk for the complement factor H ( CFH ) gene family
Year: 2018
Type: article
Study design: Observational Study
Abstract: Significance Genetic variation of the complement factor H ( CFH ) gene family is associated with several complex diseases. Here, we have performed both long- and short-read sequencing of multiple humans and nonhuman primates in an effort to understand its complex evolutionary history. We find that this locus has evolved predominantly through incomplete segmental duplication and identify recurrent reuse of donor and acceptor duplications leading to CFHR fusion genes with diverse functions. Investigation of a large cohort of patients with age-related macular degeneration revealed multiple structural variation breakpoints and mutational burdens that cluster in specific domains of the CFH protein. These domains overlap sites showing signatures of natural selection, providing strong evidence for the shared role of selective pressure on diversity and disease.
Authors: Stuart Cantsilieris, Bradley J. Nelson, John Huddleston, Carl Baker, Lana Harshman, Kelsi Penewit, Katherine M. Munson, Melanie Sorensen, AnneMarie E. Welch, Vy Dang, Felix Grassmann, Andrea J. Richardson, Robyn H. Guymer, Tina A. Graves-Lindsay, Richard K. Wilson, Bernhard H. F. Weber, Paul N. Baird, Rando Allikmets, Evan E. Eichler
Institutions: University of Washington, Howard Hughes Medical Institute, University of Regensburg, The University of Melbourne, The Royal Victorian Eye & Ear Hospital, Centre for Eye Research Australia, Washington University in St. Louis, Nationwide Children's Hospital, The Ohio State University, Columbia University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Awards: Genetic Susceptibility to Age-Related Macular Degeneration, Improving the Human Reference Genome Resource, Core Facilities for Vision Research, Defining the role of Genetic Variants in Systemic Lupus Erythematosus: Copy Number Variants and Epigenetic Mechanisms, Pathways to precision medicine in eye disease, G9000231942, Long-read sequence and assembly of segmental duplications
OpenAlex ID: W2801661300