Allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants.
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Publication Date
2022-02-17Journal Title
Elife
ISSN
2050-084X
Publisher
eLife Sciences Publications, Ltd
Volume
11
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
White, R. J., Mackay, E., Wilson, S. W., & Busch-Nentwich, E. M. (2022). Allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants.. Elife, 11 https://doi.org/10.7554/eLife.72825
Abstract
In model organisms, RNA-sequencing (RNA-seq) is frequently used to assess the effect of genetic mutations on cellular and developmental processes. Typically, animals heterozygous for a mutation are crossed to produce offspring with different genotypes. Resultant embryos are grouped by genotype to compare homozygous mutant embryos to heterozygous and wild-type siblings. Genes that are differentially expressed between the groups are assumed to reveal insights into the pathways affected by the mutation. Here we show that in zebrafish, differentially expressed genes are often over-represented on the same chromosome as the mutation due to different levels of expression of alleles from different genetic backgrounds. Using an incross of haplotype-resolved wild-type fish, we found evidence of widespread allele-specific expression, which appears as differential expression when comparing embryos homozygous for a region of the genome to their siblings. When analysing mutant transcriptomes, this means that the differential expression of genes on the same chromosome as a mutation of interest may not be caused by that mutation. Typically, the genomic location of a differentially expressed gene is not considered when interpreting its importance with respect to the phenotype. This could lead to pathways being erroneously implicated or overlooked due to the noise of spurious differentially expressed genes on the same chromosome as the mutation. These observations have implications for the interpretation of RNA-seq experiments involving outbred animals and non-inbred model organisms.
Keywords
Zebrafish, Differential expression, chromosomes, mutants, developmental biology, Gene Expression, Rna-seq, Allele-specific Expression
Sponsorship
Medical Research Council (MR/T020164/1, MR/L003775/1)
Wellcome Trust (095722/Z/11/Z, 206194)
Identifiers
35175196, PMC8884726
External DOI: https://doi.org/10.7554/eLife.72825
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335242
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