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| 2. |
- Berglund, Jonas, et al.
(författare)
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Novel origins of copy number variation in the dog genome
- 2012
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X .- 1474-7596. ; 13:8, s. R73-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. RESULTS: We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. CONCLUSIONS: A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution.
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| 3. |
- Bornelöv, Susanne, 1984-, et al.
(författare)
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Correspondence on Lovell et al. : identification of chicken genes previously assumed to be evolutionarily lost
- 2017
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X .- 1474-7596. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Through RNA-Seq analyses, we identified 137 genes that are missing in chicken, including the long-sought-after nephrin and tumor necrosis factor genes. These genes tended to cluster in GC-rich regions that have poor coverage in genome sequence databases. Hence, the occurrence of syntenic groups of vertebrate genes that have not been observed in Aves does not prove the evolutionary loss of such genes.
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| 4. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 5. |
- Karlsson, Elinor K, et al.
(författare)
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Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B
- 2013
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X .- 1474-7596. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Canine osteosarcoma is clinically nearly identical to the human disease, but is common and highly heritable, making genetic dissection feasible.RESULTS: Through genome-wide association analyses in three breeds (greyhounds, Rottweilers, and Irish wolfhounds), we identify 33 inherited risk loci explaining 55% to 85% of phenotype variance in each breed. The greyhound locus exhibiting the strongest association, located 150 kilobases upstream of the genes CDKN2A/B, is also the most rearranged locus in canine osteosarcoma tumors. The top germline candidate variant is found at a >90% frequency in Rottweilers and Irish wolfhounds, and alters an evolutionarily constrained element that we show has strong enhancer activity in human osteosarcoma cells. In all three breeds, osteosarcoma-associated loci and regions of reduced heterozygosity are enriched for genes in pathways connected to bone differentiation and growth. Several pathways, including one of genes regulated by miR124, are also enriched for somatic copy-number changes in tumors.CONCLUSIONS: Mapping a complex cancer in multiple dog breeds reveals a polygenic spectrum of germline risk factors pointing to specific pathways as drivers of disease.
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| 6. |
- Nilsson, Björn, et al.
(författare)
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An improved method for detecting and delineating genomic regions with altered gene expression in cancer
- 2008
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Ingår i: GENOME BIOL. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 9:1, s. R13-
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Tidskriftsartikel (refereegranskat)abstract
- Genomic regions with altered gene expression are a characteristic feature of cancer cells. We present a novel method for identifying such regions in gene expression maps. This method is based on total variation minimization, a classical signal restoration technique. In systematic evaluations, we show that our method combines top-notch detection performance with an ability to delineate relevant regions without excessive over-segmentation, making it a significant advance over existing methods. Software (Rendersome) is provided.
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| 7. |
- Nilsson, Björn, et al.
(författare)
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Threshold-free high-power methods for the ontological analysis of genome-wide gene expression studies
- 2007
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 8:5, s. R74-
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Tidskriftsartikel (refereegranskat)abstract
- Ontological analysis facilitates microarray data interpretation. We describe new ontological analysis methods which, unlike existing approaches, are threshold-free and statistically powerful. We perform extensive evaluations and introduce a new concept, detection spectra, to characterize methods. We show that different ontological analysis methods exhibit distinct detection spectra, and that it is critical to account for this diversity. Our results argue strongly against the continued use of existing methods, and provide directions towards an enhanced approach.
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| 8. |
- Pochon, Zoé, et al.
(författare)
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aMeta : an accurate and memory-efficient ancient metagenomic profiling workflow
- 2023
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of microbial data from archaeological samples is a growing field with great potential for understanding ancient environments, lifestyles, and diseases. However, high error rates have been a challenge in ancient metagenomics, and the availability of computational frameworks that meet the demands of the field is limited. Here, we propose aMeta, an accurate metagenomic profiling workflow for ancient DNA designed to minimize the amount of false discoveries and computer memory requirements. Using simulated data, we benchmark aMeta against a current state-of-the-art workflow and demonstrate its superiority in microbial detection and authentication, as well as substantially lower usage of computer memory.
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| 9. |
- Sandve, Geir K., et al.
(författare)
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The Genomic HyperBrowser: Inferential genomics at the sequence level
- 2010
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1474-760X .- 1465-6906. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The immense increase in the generation of genomic scale data poses an unmet analytical challenge, due to a lack of established methodology with the required flexibility and power. We propose a first principled approach to statistical analysis of sequence-level genomic information. We provide a growing collection of generic biological investigations that query pairwise relations between tracks, represented as mathematical objects, along the genome. The Genomic HyperBrowser implements the approach and is available at http://hyperbrowser.uio.no.© 2010 Sandve et al.; licensee BioMed Central Ltd.
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| 10. |
- Sheng, Zheya, et al.
(författare)
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Standing genetic variation as a major contributor to adaptation in the Virginia chicken lines selection experiment.
- 2015
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X .- 1474-7596. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Artificial selection provides a powerful approach to study the genetics of adaptation. Using selective-sweep mapping, it is possible to identify genomic regions where allele-frequencies have diverged during selection. To avoid false positive signatures of selection, it is necessary to show that a sweep affects a selected trait before it can be considered adaptive. Here, we confirm candidate, genome-wide distributed selective sweeps originating from the standing genetic variation in a long-term selection experiment on high and low body weight of chickens.RESULTS: Using an intercross between the two divergent chicken lines, 16 adaptive selective sweeps were confirmed based on their association with the body weight at 56 days of age. Although individual additive effects were small, the fixation for alternative alleles across the loci contributed at least 40 % of the phenotypic difference for the selected trait between these lines. The sweeps contributed about half of the additive genetic variance present within and between the lines after 40 generations of selection, corresponding to a considerable portion of the additive genetic variance of the base population.CONCLUSIONS: Long-term, single-trait, bi-directional selection in the Virginia chicken lines has resulted in a gradual response to selection for extreme phenotypes without a drastic reduction in the genetic variation. We find that fixation of several standing genetic variants across a highly polygenic genetic architecture made a considerable contribution to long-term selection response. This provides new fundamental insights into the dynamics of standing genetic variation during long-term selection and adaptation.
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