title: The revolution in human monogenic disease mapping.
abstract: The successful completion of the Human Genome Project (HGP) was an unprecedented scientific advance that has become an invaluable resource in the search for genes that cause monogenic and common (polygenic) diseases. Prior to the HGP, linkage analysis had successfully mapped many disease genes for monogenic disorders; however, the limitations of this approach were particularly evident for identifying causative genes in rare genetic disorders affecting lifespan and/or reproductive fitness, such as skeletal dysplasias. In this review, we illustrate the challenges of mapping disease genes in such conditions through the ultra-rare disorder fibrodysplasia ossificans progressiva (FOP) and we discuss the advances that are being made through current massively parallel ("next generation") sequencing (MPS) technologies.
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, 37 Kent Road, Woolloongabba, Brisbane 4102, Queensland, Australia. emma.duncan@uq.edu.au.
authors.forename: Emma
authors.initials: E
authors.lastname: Duncan
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, 37 Kent Road, Woolloongabba, Brisbane 4102, Queensland, Australia. matt.brown@uq.edu.au.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brown
authors.affiliation: Center for Research in FOP and Related Disorders, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA 19104, USA. shore@mail.med.upenn.edu.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore