Genetic Analysis of Hematological Parameters in Incipient Lines of the Collaborative Cross

G3: Genes, Genomes, Genetics

Urraca Tavarez¹  David W. Threadgill⁶  Elissa J. Chesler²  Francis S. Collins¹  Bailey C. E. Peck¹  Fernando Pardo-Manuel de Villena⁴  Gary A. Churchill⁴  David L. Aylor³  Samir N. P. Kelada¹  Darla R. Miller⁵  Joseph F. Ryan¹  Ryan J. Buus³ 

[1] Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892;Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831The Jackson Laboratory, Bar Harbor, Maine 04609Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831The Jackson Laboratory, Bar Harbor, Maine 04609The Jackson Laboratory, Bar Harbor, Maine 04609Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831The Jackson Laboratory, Bar Harbor, Maine 04609;Department of Genetics, The University of North Carolina, Chapel Hill, North Carolina 27599Department of Genetics, The University of North Carolina, Chapel Hill, North Carolina 27599Department of Genetics, The University of North Carolina, Chapel Hill, North Carolina 27599;The Jackson Laboratory, Bar Harbor, Maine 04609The Jackson Laboratory, Bar Harbor, Maine 04609The Jackson Laboratory, Bar Harbor, Maine 04609;Department of Genetics, The University of North Carolina, Chapel Hill, North Carolina 27599Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831Department of Genetics, The University of North Carolina, Chapel Hill, North Carolina 27599Department of Genetics, The University of North Carolina, Chapel Hill, North Carolina 27599Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831Department of Genetics, The University of North Carolina, Chapel Hill, North Carolina 27599Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831;Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695

关键词: Mouse Genetic Resource;    Mouse Collaborative Cross;    hematology;    hemoglobin β;    mean red cell volume;    QTL;    mouse genetics;    complex traits;    shared ancestry;   

DOI  :  10.1534/g3.111.001776

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

Hematological parameters, including red and white blood cell counts and hemoglobin concentration, are widely used clinical indicators of health and disease. These traits are tightly regulated in healthy individuals and are under genetic control. Mutations in key genes that affect hematological parameters have important phenotypic consequences, including multiple variants that affect susceptibility to malarial disease. However, most variation in hematological traits is continuous and is presumably influenced by multiple loci and variants with small phenotypic effects. We used a newly developed mouse resource population, the Collaborative Cross (CC), to identify genetic determinants of hematological parameters. We surveyed the eight founder strains of the CC and performed a mapping study using 131 incipient lines of the CC. Genome scans identified quantitative trait loci for several hematological parameters, including mean red cell volume (Chr 7 and Chr 14), white blood cell count (Chr 18), percent neutrophils/lymphocytes (Chr 11), and monocyte number (Chr 1). We used evolutionary principles and unique bioinformatics resources to reduce the size of candidate intervals and to view functional variation in the context of phylogeny. Many quantitative trait loci regions could be narrowed sufficiently to identify a small number of promising candidate genes. This approach not only expands our knowledge about hematological traits but also demonstrates the unique ability of the CC to elucidate the genetic architecture of complex traits.

【 授权许可】

Unknown