{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:46:37Z","timestamp":1781210797729,"version":"3.54.1"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,12,24]]},"abstract":"<jats:p>\n                    Type 1 von Willebrand disease (VWD), characterized by reduced\n levels of plasma von Willebrand factor (VWF), is the most common\n inherited bleeding disorder in humans. Penetrance of VWD is incomplete,\n and expression of the bleeding phenotype is highly variable. In\n addition, plasma VWF levels vary widely among normal individuals. To\n identify genes that influence VWF level, we analyzed a genetic cross\n between RIIIS\/J and CASA\/Rk, two strains of mice that exhibit a 20-fold\n difference in plasma VWF level. DNA samples from F\n                    <jats:sub>2<\/jats:sub>\n                    progeny\n demonstrating either extremely high or extremely low plasma VWF levels\n were pooled and genotyped for 41 markers spanning the autosomal genome.\n A novel locus accounting for 63% of the total variance in VWF level\n was mapped to distal mouse chromosome 11, which is distinct from the\n murine\n                    <jats:italic>Vwf<\/jats:italic>\n                    locus on chromosome 6. We designated this\n locus\n                    <jats:italic>Mvwf<\/jats:italic>\n                    for \u201cmodifier of VWF.\u201d Additional\n genotyping of as many as 2407 meioses established a high resolution\n genetic map with gene order\n                    <jats:italic>Cola1<\/jats:italic>\n                    -\n                    <jats:italic>Itg3a<\/jats:italic>\n                    -\n                    <jats:italic>Ngfr<\/jats:italic>\n                    -\n                    <jats:italic>Mvwf<\/jats:italic>\n                    \/\n                    <jats:italic>Gip<\/jats:italic>\n                    -\n                    <jats:italic>Hoxb9<\/jats:italic>\n                    -\n                    <jats:italic>Hoxb1<\/jats:italic>\n                    -\n                    <jats:italic>Cbx<\/jats:italic>\n                    \u00b7\n                    <jats:italic>rs2<\/jats:italic>\n                    -\n                    <jats:italic>Cox5a<\/jats:italic>\n                    -\n                    <jats:italic>Gfap<\/jats:italic>\n                    .\n The\n                    <jats:italic>Mvwf<\/jats:italic>\n                    candidate interval between\n                    <jats:italic>Ngfr<\/jats:italic>\n                    and\n                    <jats:italic>Hoxb9<\/jats:italic>\n                    is \u22480.5 centimorgan (cM). These results\n demonstrate that a single dominant gene accounts for the low VWF\n phenotype of RIIIS\/J mice in crosses with several other strains. The\n pattern of inheritance suggests a gain-of-function mutation in a unique\n component of VWF biosynthesis or processing. Characterization of the\n human homologue for\n                    <jats:italic>Mvwf<\/jats:italic>\n                    may have relevance for a subset\n of type 1 VWD cases and may define an important genetic factor\n modifying penetrance and expression of mutations at the\n                    <jats:italic>VWF<\/jats:italic>\n                    locus.\n                  <\/jats:p>","DOI":"10.1073\/pnas.93.26.15352","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"15352-15357","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["A novel modifier gene for plasma von Willebrand factor level maps to distal mouse chromosome\u200911"],"prefix":"10.1073","volume":"93","author":[{"given":"Karen\u2009L.","family":"Mohlke","sequence":"first","affiliation":[{"name":"Departments of Human Genetics, Internal Medicine, and\r Surgery and Howard Hughes Medical Institute, University\r of Michigan Medical School, Ann Arbor, MI 48109; and\r Department of Molecular and Cellular Biology, Roswell Park\r Memorial Institute, Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William\u2009C.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics, Internal Medicine, and\r Surgery and Howard Hughes Medical Institute, University\r of Michigan Medical School, Ann Arbor, MI 48109; and\r Department of Molecular and Cellular Biology, Roswell Park\r Memorial Institute, Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randal\u2009J.","family":"Westrick","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics, Internal Medicine, and\r Surgery and Howard Hughes Medical Institute, University\r of Michigan Medical School, Ann Arbor, MI 48109; and\r Department of Molecular and Cellular Biology, Roswell Park\r Memorial Institute, Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward\u2009K.","family":"Novak","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics, Internal Medicine, and\r Surgery and Howard Hughes Medical Institute, University\r of Michigan Medical School, Ann Arbor, MI 48109; and\r Department of Molecular and Cellular Biology, Roswell Park\r Memorial Institute, Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen\u2009A.","family":"Cooney","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics, Internal Medicine, and\r Surgery and Howard Hughes Medical Institute, University\r of Michigan Medical School, Ann Arbor, MI 48109; and\r Department of Molecular and Cellular Biology, Roswell Park\r Memorial Institute, Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard\u2009T.","family":"Swank","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics, Internal Medicine, and\r Surgery and Howard Hughes Medical Institute, University\r of Michigan Medical School, Ann Arbor, MI 48109; and\r Department of Molecular and Cellular Biology, Roswell Park\r Memorial Institute, Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ginsburg","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics, Internal Medicine, and\r Surgery and Howard Hughes Medical Institute, University\r of Michigan Medical School, Ann Arbor, MI 48109; and\r Department of Molecular and Cellular Biology, Roswell Park\r Memorial Institute, Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,12,24]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.10.2507.bloodjournal79102507"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V69.2.454.454"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80384-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V54.1.117.117"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V69.6.1691.1691"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.4.990.990"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V63.3.657.657"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(82)90729-X"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(12)61202-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-97-5-713"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","unstructured":"Dalton R.\u2009G. 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