From 3348fd008296dc7abf09ee2ccd19569aa34188f2 Mon Sep 17 00:00:00 2001 From: Tom Sasani Date: Tue, 24 Oct 2023 16:17:07 -0400 Subject: [PATCH] Add caveat about unannotated genes in interval. --- content/03.results.md | 7 +++++-- 1 file changed, 5 insertions(+), 2 deletions(-) diff --git a/content/03.results.md b/content/03.results.md index c1d93ac..ae40579 100644 --- a/content/03.results.md +++ b/content/03.results.md @@ -64,8 +64,11 @@ This signal was specific to BXDs with *D* genotypes at the `rs27509845` locus, a The peak markers on chromosome 4 and 6 did not exhibit strong linkage disequilibrium ($R^2$ = 4e-5). We also performed QTL scans for the fractions of each 1-mer mutation type using the same mutation data, but none produced a genome-wide significant log-odds score at any locus (Figure {@fig:qtl-scans}; *Materials and Methods*). -We queried the region surrounding the top marker on chromosome 6 (+/- the 90% bootstrap confidence interval) and discovered 64 protein-coding genes, of which four were annotated with a Gene Ontology [@PMID:10802651;@PMID:33290552] term related to "DNA repair": *Fancd2*, *Ogg1*, *Setmar*, and *Rad18*. -Of these, two harbored nonsynonymous differences between the parental C57BL/6J and DBA/2J strains (Table @tbl:nonsyn-diffs). +We queried the region surrounding the top marker on chromosome 6 (+/- the 90% bootstrap confidence interval) and discovered 64 protein-coding genes, of which four were annotated with a Gene Ontology (GO) [@PMID:10802651;@PMID:33290552] term related to "DNA repair": *Fancd2*, *Ogg1*, *Setmar*, and *Rad18*. +None of the remaining genes were annotated with a cellular function that would obviously contribute to a germline mutator phenotype; however, many of these GO annotations are imperfect and/or incomplete. +Although we focus our analysis on DNA repair genes, it remains possible that other genes within the confidence interval could underlie the C>A mutator phenotype we identified in the BXDs. + +Of the annotated DNA repair genes within the confidence interval, two harbored nonsynonymous differences between the parental C57BL/6J and DBA/2J strains (Table @tbl:nonsyn-diffs). *Ogg1* encodes a key member of the base-excision repair response to oxidative DNA damage (a pathway that also includes *Mutyh*), and in mice *Setmar* encodes a SET domain-containing histone methyltransferase; both *Ogg1* and *Setmar* are expressed in mouse gonadal cells. Because the bootstrap can exhibit poor coverage in QTL mapping studies [@PMID:16783000], we also scanned an interval +/- 5 Mbp from the peak AMSD marker on chromosome 6 for additional candidate genes. Although the choice of a 10 Mbp interval is somewhat arbitrary, the interval does contain a plausible candidate: *Mbd4*, a protein-coding gene involved in base excision repair that also harbors a non-synonymous difference between the BXD parental strains (Table @tbl:nonsyn-diffs).