5 Results
for term "sites"
- Genetic Architectures of Quantitative Variation in RNA Editing Pathways...the specicity and degree of editing are not well understood. We examined quantitative variation of site-specic editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specic sites for A ~~~
Figure 1Mapping of C-to-U and A-to-I RNA editing reveals distinct patterns of genetic regulation. (A) Marker location (horizontal axis) vs. editing-site location (vertical axis) for the C-to-U editing sites shows that editing variation is due to genetic variants near the editing site (diagonal band) and at a location on chromosome 6 (vertical band). Open circles show sites from the RADAR or DARNED databases, and closed circles show sites from the de novo editing site discover. (B) Marker location vs. editing-site location for the A-to-I edit sites shows that editing variation is primarily due to genetic variants near the editing site. Note that some points represent multiple overlapping editing sites.
Figure 2Mean C-to-U editing ratios for most editing sites map to a region on chromosome 6 at 122 Mb. (A) Genome scan of mean C-to-U editing for 70 editing sites shows a strong association on chromosome 6. Horizontal axis shows the mouse genome; vertical axis plots the LOD score. Red line is the permutation-derived α = 0.05 significance threshold. (B) Founder allele effects on chromosome 6 reveal a complex pattern of allele effects. Horizontal axis shows chromosome 6 in Mb. Vertical axis shows the founder allele effects.
Figure 4Genomic variants in the DO founders fit the pattern of Apob editing. (A) A nonsynonymous SNP in exon 6 of Apobec1 contributed by CAST/EiJ and PWK/PhJ converts an arginine (R) residue to a glutamine (Q), highlighted in red. Residues in the active site are highlighted in blue. (B) Most mammals have a glutamine residue at this location. Shannon entropy for each base position shows that the glutamine is somewhat conserved. (C) RNA-seq pileups of Apobec1 in the eight DO founders show transcriptional variation between alleles. C57BL/6J and NZO/HlLtJ alleles carry an insertion (shaded in red) in the fifth intron that overlaps a retained intron. 129S1/SvImJ, A/J, and NOD/ShiLtJ alleles carry a SNP (red box) in the 5′ UTR of exon 4 that has increased expression in those strains. The y-axis shows the read depth normalized to library size. (D) Consensus mooring sequence motif for C-to-U edited genes. (Top) The Apobec1 mooring sequence. (Bottom) The consensus binding motif discovered using MEME. (E) Sequence information content around the edited C-to-U site shows that bases at the proximal and distal positions are either A or U. There does not appear to be sequence preference at other nearby base positions.
Figure 5Structural differences between the founder strains may influence A-to-I editing efficiency. (A) Founder allele effects for 0610005C13Rik show that DO mice carrying the NZO/HlLtJ allele have more edited transcripts. (B) Among the DO founder strains, NZO/HlLtJ has the highest editing ratio. (C) RNA secondary structure of the full mRNA for 0610005C13Rik for C57BL/6J and NZO/HlLtJ shows that the NZO/HlLtJ strain contains a longer dsRNA region around the editing sites. The location of the editing sites on the full-length RNA is circled; the nucleotides around the editing site are enlarged and outlined by rectangles. (D) Founder allele effects for Lact2b show that DO mice carrying the PWK/PhJ allele have lower editing. (E) Among the DO founder strains, PWK/PhJ has the lowest editing ratio. (F) Full-length mRNA for Lact2b in C57BL/6J and PWK/PhJ shows that PWK/PhJ carries a shorter dsRNA region near the editing sites. (G) Founder allele effects for 2010106G01Rik in DO mice show a complex pattern of editing ratios, with NOD/ShiLtJ having high editing and CAST/EiJ having low editing. (H) Editing ratios. The founders are similar to the allele effects observed in the DO population but differ in the order of editing ratios. (I) Full-length mRNA for 2010106G01Rik shows that the dsRNA region around the editing sites is slightly shorter in CAST/EiJ.