sex specific gene regulation and expression qtls in mouse macrophages from a strain intercross性特定基因调控和表达法在小鼠巨噬细胞应变交叉.pdfVIP

Sex Specific Gene Regulation and Expression QTLs in Mouse Macrophages from a Strain Intercross 1 1 1 1 2 1,3 Jeffrey M. Bhasin , Enakshi Chakrabarti , Dao-Quan Peng , Aneesh Kulkarni , Xi Chen , Jonathan D. Smith * 1 Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio, United States of America, 2 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States of America, 3 Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States of America Background. A powerful way to identify genes for complex traits it to combine genetic and genomic methods. Many trait quantitative trait loci (QTLs) for complex traits are sex specific, but the reason for this is not well understood. Methodology/ Principal Findings. RNA was prepared from bone marrow derived macrophages of 93 female and 114 male F2 mice derived from a strain intercross between apoE-deficient mice on the AKR and DBA/2 genetic backgrounds, and was subjected to transcriptome profiling using microarrays. A high density genome scan was performed using a mouse SNP chip, and expression QTLs (eQTLs) were located for expressed transcripts. Using suggestive and significant LOD score cutoffs of 3.0 and 4.3, respectively, thousands of eQTLs in the female and male cohorts were identified. At the suggestive LOD threshold the majority of the eQTLs were trans eQTLs, mapping unlinked to the position of the gene. Cis eQTLs, which mapped to the location of the gene, had much higher LOD scores than trans eQTLs, indicating their more direct effect on gene expression. The majority of cis eQTLs were common to both males and females, but only ,1% of the trans eQTLs were shared by both sexes. At the significant LOD threshold,