Point mutations and complex variants impact gene expression and addiction-related behaviors in Heterogeneous Stock rats
While various variants, including single nucleotide polymorphisms (SNPs), small insertions/deletions, short tandem repeats and structural variants, drive individual genetic differences, their influence on gene expression and complex traits remains unclear. We used short- and long-read sequencing to generate a comprehensive variant catalog in Heterogeneous Stock (HS) rats and performed joint…
Point mutations and complex variants play a significant role in influencing gene expression and addiction-related behaviors in Heterogeneous Stock (HS) rats. Researchers utilized short- and long-read sequencing techniques to create an extensive variant catalog within these rats, subsequently conducting joint cis-expression quantitative trait loci (cis-eQTL) mapping across five brain regions.
The findings revealed that non-single nucleotide polymorphism (non-SNP) variants contributed to more than half of the primary regulatory associations identified. Many of these non-SNP variants were not effectively tagged by adjacent single nucleotide polymorphisms (SNPs) due to a lack of linkage disequilibrium (LD). Upon comparing joint and SNP-only analyses, it was discovered that over 46% of eQTL genes that were shared between the two approaches had a non-SNP lead cis-eQTL, while fewer than half were strongly linked to the corresponding lead SNP.
By linking joint cis-eQTLs to complex trait associations, the researchers uncovered mechanisms that were not identified through SNP-only approaches. This highlights the critical importance of integrating various types of variants into genetic studies, providing a valuable resource for the HS rat community that enhances our understanding of gene expression and addiction-related behaviors.
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