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Transcriptome analysis of homozygous mutants compared to their wild-type siblings and the impact of non-isogenic genetic backgrounds on gene expression. A) Experimental selection of progeny homozygous for a mutant allele of a gene-of-interest (GOI, mutation-bearing chromosome indicated in red) necessarily involves increased homozygosity for alleles of genes linked to that mutation (i.e. on the same chromosome). The rates of transcription or transcript degradation for these alleles may differ significantly from their corresponding alleles on the homologous wild-type chromosomes (shaded differentially to illustrate that these wild-type chromosomes are not isogenic). B) Differential expression of alleles of a linked bystander gene, LG, between wild-type and mutant chromosomes due to a functional interaction between the GOI and the LG. C) eQTL-driven differential expression of LG between wild-type and homozygous mutant chromosomes in the absence of a functional interaction between the GOI and the LG. The expression of LG differs independently of the GOI genotype when LG’s different alleles are eQTLs. D) Breeding to produce genotype groups (e.g., homozygous GOI mutants for comparison to wild-type) selects for differential representation between those groups for the alleles of neighbouring LGs. When those alleles are eQTLs, they can show differential expression between the groups that is not a phenotypic effect of the mutation but can, mistakenly, be inferred as such. Zebrafish icons used in this image were obtained from https://bioicons.com and have been modified from DBCLS https://togotv.dbcls.jp/en/pics.html, licensed under CC-BY 4.0 Unported https://creativecommons.org/licenses/by/4.0/.
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