Jun 15, 2015

Identification of Slco1a6 as a candidate gene that broadly affects gene expression in mouse pancreatic islets

BioRxiv : the Preprint Server for Biology
Jianan TianAlan D Attie

Abstract

We surveyed gene expression in six tissues in an F2 intercross between mouse strains C57BL/6J (abbreviated B6) and BTBR T+ tf /J (abbreviated BTBR) made genetically obese with the Leptin(ob) mutation. We identified a number of expression quantitative trait loci (eQTL) affecting the expression of numerous genes distal to the locus, called trans-eQTL hotspots. Some of these trans-eQTL hotspots showed effects in multiple tissues, whereas some were specific to a single tissue. An unusually large number of transcripts (7% of genes) mapped in trans to a hotspot on chromosome 6, specifically in pancreatic islets. By considering the first two principal components of the expression of genes mapping to this region, we were able to convert the multivariate phenotype into a simple Mendelian trait. Fine-mapping the locus by traditional methods reduced the QTL interval to a 298 kb region containing only three genes, including Slco1a6, one member of a large family of organic anion transporters. Direct genomic sequencing of all Slco1a6 exons identified a non-synonymous coding SNP that converts a highly conserved proline residue at amino acid position 564 to serine. Molecular modeling suggests that Pro564 faces an aqueous pore within this 12-tr...Continue Reading

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Mentioned in this Paper

Quantitative Trait Loci
Positioning Attribute
Bile Acid Measurement
HEK293 Cells
Organic Anion Transporters
Exons
Genome
Genes
Integral Membrane Proteins
Molecular Modeling

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