부산대학교 도서관

Using chromosome substitution strains ( CSS), we previously identified a large quantitative trait locus ( QTL) for conditioned fear ( CF) on mouse chromosome 10. Here, we used an F2 cross between CSS-10 and C57BL/ 6J ( B6) to localize that QTL to distal chromosome 10. That QTL accounted for all the difference between CSS-10 and B6. We then produced congenic strains to fine-map that interval. We identified two congenic strains that captured some or all the QTL. The larger congenic strain (Line 1: 122.387121-129.068 Mb; build 37) appeared to account for all the difference between CSS-10 and B6. The smaller congenic strain (Line 2: 127.277-129.068 Mb) was intermediate between CSS-10 and B6. We used haplotype mapping followed by quantitative polymerase chain reaction to identify one gene that was differentially expressed in both lines relative to B6 ( Rnf41) and one that was differentially expressed between only Line 1 and B6 ( Shmt2). These cis- eQTLs may cause the behavioral QTLs; however, further studies are required to validate these candidate genes. More generally, our observation that a large QTL mapped using CSS and F2 crosses can be dissected into multiple smaller QTLs shows a weaknesses of two-stage approaches that seek to use coarse mapping to identify large regions followed by fine-mapping. Indeed, additional dissection of these congenic strains might result in further subdivision of these QTL regions. Despite these limitations, we have successfully fine-mapped two QTLs to small regions and identified putative candidate genes, showing that the congenic approach can be effective for fine-mapping QTLs. [ABSTRACT FROM AUTHOR]