{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:55:54Z","timestamp":1775976954407,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011868","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013918","name":"Sanfilippo Children's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013918","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Carthew Family Charity Trust"},{"name":"Race Against Dementia"},{"name":"Australian Government Research Training Program"},{"name":"NIH","award":["R35 GM139635"],"award-info":[{"award-number":["R35 GM139635"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    In comparisons between mutant and wild-type genotypes, transcriptome analysis can reveal the direct impacts of a mutation, together with the homeostatic responses of the biological system. Recent studies have highlighted that, when the effects of homozygosity for recessive mutations are studied in non-isogenic backgrounds, genes located proximal to the mutation on the same chromosome often appear over-represented among those genes identified as differentially expressed (DE). One hypothesis suggests that DE genes chromosomally linked to a mutation may not reflect functional responses to the mutation but, instead, result from an unequal distribution of expression quantitative trait loci (eQTLs) between sample groups of mutant or wild-type genotypes. This is problematic because eQTL expression differences are difficult to distinguish from genes that are DE due to functional responses to a mutation. Here we show that chromosomally co-located differentially expressed genes (CC-DEGs) are also observed in analyses of dominant mutations in heterozygotes. We define a method and a metric to quantify, in RNA-sequencing data, localised differential allelic representation (DAR) between those sample groups subjected to differential expression analysis. We show how the DAR metric can predict regions prone to eQTL-driven differential expression, and how it can improve functional enrichment analyses through gene exclusion or weighting-based approaches. Advantageously, this improved ability to identify probable eQTLs also reveals examples of CC-DEGs that are likely to be functionally related to a mutant phenotype. This supports a long-standing prediction that selection for advantageous linkage disequilibrium influences chromosome evolution. By comparing the genomes of zebrafish (\n                    <jats:italic>Danio rerio<\/jats:italic>\n                    ) and medaka (\n                    <jats:italic>Oryzias latipes<\/jats:italic>\n                    ), a teleost with a conserved ancestral karyotype, we find possible examples of chromosomal aggregation of CC-DEGs during evolution of the zebrafish lineage. Our method for DAR analysis requires only RNA-sequencing data, facilitating its application across new and existing datasets.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1011868","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T13:36:38Z","timestamp":1707744998000},"page":"e1011868","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential allelic representation (DAR) identifies candidate eQTLs and improves transcriptome 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