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Candidate Genes for Thrombosis Susceptibility on Mouse Chromosome 5
Author(s) -
HooverPlow Jane,
Chao Ryan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.662.7
Subject(s) - biology , ptpn11 , candidate gene , genetics , gene , platelet , quantitative trait locus , immunology , mutation , kras
Susceptibility to thrombosis varies in human populations as well as many inbred mouse strains. To identify novel genetic determinates of thrombosis, a panel of chromosome substitution strains, C57BL/6J‐Chr 1–21 A/J , was screened with a tail bleeding/rebleeding assay, a reporter assay for hemostasis and thrombosis. On chromosome 5 a significant (P < 0.0009) QTL was found at marker D5Mi338 (59 cm) for clot stability time (time between first and second bleeding). Using an annotation database (DAVID), six candidate genes were identified: hps4, vps33a, sh2b3, ptpn11, adam1a, and adam1b that are associated with platelet functions, hematopoiesis, and blood coagulation. Polymorphisms in Hps4 and Vps33a genes are associated with Hermansky‐Pudlak syndrome type 4 and the absence platelet dense granules. Proteins of Sh2b3 and Vps33a genes are involved in intracellular signaling pathways and intracellular protein sorting. Ptpn11 is a member of the protein tyrosine phosphatase family, and mutations are identified with Noonan syndrome, one of the most common genetic disorders of congenital heart defects. Adam1a and Adam1b , disintergrin/metallopeptidase proteins, are important for spermatogenesis and suggested to play a role in blood coagulation. Identification of novel thrombotic susceptibility genes and their homology in humans may uncover new diagnostic and therapeutic factors of thrombotic risk. NIH, AHA.