Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: The motif composition of variable-number tandem repeats impacts gene expression Understanding the impact of DNA variation on human traits is a fundamental question in human genetics. Variable number tandem repeats (VNTRs) make up roughly 3% of the human genome but are often excluded from association analysis due to poor read mappability or divergent repeat content. While methods exist to estimate VNTR length from short-read data, it is known that VNTRs vary in both length and repeat (motif) composition. Here, we use a repeat-pangenome graph (RPGG) constructed on 35 haplotype-resolved assemblies to detect variation in both VNTR length and repeat composition. We align population scale data from the Genotype-Tissue Expression (GTEx) Consortium to examine how variations in sequence composition may be linked to expression, including cases independent of overall VNTR length. We find that 20,834 VNTRs are associated with nearby gene expression through motif variations, of which only 5.1% associations are accessible from length. Fine-mapping identifies 273 genes to be likely driven by variation in certain VNTR motifs and not overall length. To demonstrate the utility of association using VNTR motifs, we examine the intronic VNTR of CACNA1C, which has been reported to be associated with schizophrenia risk through motif variation. We show that in healthy populations a previously identified schizophrenia risk motif is associated with decreased expression of CACNA1C, and detect an additional novel motif with similar effect.
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The categories of this paper are: communication
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The categories of this paper are: pharmacology
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The categories of this paper are: neuroscience
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The categories of this paper are: developmental
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The categories of this paper are: genetics
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The categories of this paper are: molecular
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The categories of this paper are: systems
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The categories of this paper are: epidemiology
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The categories of this paper are: cancer
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The categories of this paper are: physiology
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The categories of this paper are: education
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The categories of this paper are: bioengineering
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The categories of this paper are: bioinformatics
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The categories of this paper are: and
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The categories of this paper are: cell
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The categories of this paper are: evolutionary