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Chunk #39 — Discussion

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Dissection of a QTL hotspot on mouse distal chromosome 1 that modulates neurobehavioral phenotypes and gene expression.
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Qrr1 is a complex regulatory region that modulates expression of many genes and classical phenotypes. By exploiting a variety of microarray datasets and by applying a combination of high-resolution mapping, sequence analysis, and multiple cross analysis, we have dissected Qrr1 into segments that are primarily responsible for variation in the expression of functionally coherent sets of transcripts. The distal portion of Qrr1 (Qrr1d) has a strong trans-effect on RNA metabolism, translation, tRNA aminoacylation, and transcripts that are transported into neuronal dendrites. Fmn2, Rgs7, and a cluster of tRNAs are strong candidates in Qrr1d. We analyzed gene expression changes in the CNS of Fmn2-null mice and detected a profound effect on the expression of a small number of transcripts that map to Qrr1d, particularly on the expression of the transcription factor Pou6f1. We have shown that the FMN2 protein is highly expressed in the cell body and processes of neurons, and is a high priority candidate in Qrr1d.