Biology subjects

Orjan Carlborg

Publications and source records attributed to Orjan Carlborg.

3 recordsLinked to original sources

bioRxiv2016

Imputation-based fine-mapping suggests that most QTL in an outbred chicken Advanced Intercross Line are due to multiple, linked loci

AO_SCPLOWBSTRACTC_SCPLOWThe Virginia chicken lines have been divergently selected for juvenile body-weight for more than 50 generations. Today, the high-and low-weight lines show a 12-fold difference for the selected trait, 56-day body-weight. These lines provide unique opportunities to study the genetic architecture of long-term, single-trait selection. Previously, several Quantitative Trait Loci (QTL) contributing to weight differences between the lines were mapped in an F2-cross between them, and these were later replicated and fine-mapped in a nine-generation advanced intercross of them. Here, we explore the possibility to further increase the fine-mapping resolution of these QTL via a pedigree-based imputation strategy that aims to better capture the haplotype-diversity in the divergently selected, but outbred, founder lines. The founders of the intercross were high-density genotyped, and then pedigree-based imputation was used to assign genotypes throughout the pedigree. Imputation increased the marker-density 20-fold in the selected QTL, providing 6911 markers for the subsequent analysis. Both single-marker association and multi-marker backward-elimination analyses were used to detect associations to 56-day body-weight. The approach revealed several statistically and population-structure independent associations and increased the resolution of most QTL. Further, most QTL were also found to contain multiple independent associations, implying a complex underlying architecture due to the combined effects of multiple, linked loci on independent haplotypes that still segregate in the selected lines.\n\nArticle summaryAfter 50 generations of bi-directional selection, the Virginia chicken lines display a 12-fold difference in bodyweight at 56 days of age. Birds from the high and low selected lines were crossed to found an Advanced Intercross Line, which has been maintained for 9 generations. Using high-density genotypes of the founders, we imputed genotypes in intercross birds that were only genotyped for a sparse set of markers. Using single and multi-marker association analyses, we replicated nine known body-weight QTL. Multiple statistically independent associations were revealed in eight of the QTL, suggesting that most are caused by multiple linked loci.

Genetics↗

bioRxiv2016

Genetic regulation of transcriptional variation in natural Arabidopsis thaliana accessions

An increased knowledge of the genetic regulation of expression in Arabidopsis thaliana is likely to provide important insights about the basis of the plants extensive phenotypic variation. Here, we reanalysed two publicly available datasets with genome-wide data on genetic and transcript variation in large collections of natural A. thaliana accessions. Transcripts from more than half of all genes were detected in the leaf of all accessions, and from nearly all annotated genes in at least one accession. Thousands of genes had high transcript levels in some accessions but no transcripts at all in others and this pattern was correlated with the genome-wide genotype. In total, 2,669 eQTL were mapped in the largest population, and 717 of them were replicated in the other population. 646 cis-eQTLs regulated genes that lacked detectable transcripts in some accessions, and for 159 of these we identified one, or several, common structural variants in the populations that were shown to be likely contributors to the lack of detectable RNA-transcripts for these genes. This study thus provides new insights on the overall genetic regulation of global gene-expression diversity in the leaf of natural A. thaliana accessions. Further, it also shows that strong cis-acting polymorphisms, many of which are likely to be structural variations, make important contributions to the transcriptional variation in the worldwide A. thaliana population.

Genetics↗

bioRxiv2014

Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression

Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40 and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.

Genomics↗