caa a22 4500 44586060X CHVBK 20180317145441.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s00439-011-0984-y doi (NATIONALLICENCE)springer-10.1007/s00439-011-0984-y Delineating the Hemostaseome as an aid to individualize the analysis of the hereditary basis of thrombotic and bleeding disorders [Elektronische Daten] [Kim Fechtel, Marika Osterbur, Hildegard Kehrer-Sawatzki, Peter Stenson, David Cooper] Next-generation sequencing and genome-wide association studies represent powerful tools to identify genetic variants that confer disease risk within populations. On their own, however, they cannot provide insight into how these variants contribute to individual risk for diseases that exhibit complex inheritance, or alternatively confer health in a given individual. Even in the case of well-characterized variants that confer a significant disease risk, more healthy individuals carry the variant, with no apparent ill effect, than those who manifest disease. Access to low-cost genome sequence data promises to provide an unprecedentedly detailed view of the nature of the hereditary component of complex diseases, but requires the large-scale comparison of sequence data from individuals with and without disease to deliver a clinical calibration. The provision of informatics support remains problematic as there are currently no means to interpret the data generated. Here, we initiate this process, a prerequisite for such a study, by narrowing the focus from an entire genome to that of a single biological system. To this end, we examine the ‘Hemostaseome,' and more specifically focus on DNA sequence changes pertaining to those human genes known to impact upon hemostasis and thrombosis that can be analyzed coordinately, and on an individual basis, to interrogate how specific combinations of variants act to confer disease predisposition. As a first step, we delineate known members of the Hemostaseome and explore the nature of the genetic variants that may cause disease in individuals whose hemostatic balance has become shifted toward either a prothrombotic or anticoagulant phenotype. Springer-Verlag, 2011 Fechtel Kim 3rd Millennium Inc., 395 Totten Pond Road, Suite 201, 02451, Waltham, MA, USA aut Osterbur Marika 3rd Millennium Inc., 395 Totten Pond Road, Suite 201, 02451, Waltham, MA, USA aut Kehrer-Sawatzki Hildegard Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany aut Stenson Peter Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, CF14 4XN, Cardiff, UK aut Cooper David Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, CF14 4XN, Cardiff, UK aut Human Genetics Springer-Verlag 130/1(2011-07-01), 149-166 0340-6717 130:1<149 2011 130 439 https://doi.org/10.1007/s00439-011-0984-y text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0984-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fechtel Kim 3rd Millennium Inc., 395 Totten Pond Road, Suite 201, 02451, Waltham, MA, USA aut NATIONALLICENCE 700 1- Osterbur Marika 3rd Millennium Inc., 395 Totten Pond Road, Suite 201, 02451, Waltham, MA, USA aut NATIONALLICENCE 700 1- Kehrer-Sawatzki Hildegard Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany aut NATIONALLICENCE 700 1- Stenson Peter Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, CF14 4XN, Cardiff, UK aut NATIONALLICENCE 700 1- Cooper David Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, CF14 4XN, Cardiff, UK aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/1(2011-07-01), 149-166 0340-6717 130:1<149 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer