Publikasjoner
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Sinclair-Waters, Marion; Nome, Torfinn; Wang, Jing; Lien, Sigbjørn; Kent, Matthew Peter & Sægrov, Harald
[Vis alle 10 forfattere av denne artikkelen]
(2022).
Dissecting the loci underlying maturation timing in Atlantic salmon using haplotype and multi-SNP based association methods.
Heredity.
ISSN 0018-067X.
129(6),
s. 356–365.
doi:
10.1038/s41437-022-00570-w.
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Characterizing the role of different mutational effect sizes in the evolution of fitness-related traits has been a major goal in
evolutionary biology for a century. Such characterization in a diversity of systems, both model and non-model, will help to
understand the genetic processes underlying fitness variation. However, well-characterized genetic architectures of such traits in
wild populations remain uncommon. In this study, we used haplotype-based and multi-SNP Bayesian association methods with
sequencing data for 313 individuals from wild populations to test the mutational composition of known candidate regions for sea
age at maturation in Atlantic salmon (Salmo salar). We detected an association at five loci out of 116 candidates previously
identified in an aquaculture strain with maturation timing in wild Atlantic salmon. We found that at four of these five loci, variation
explained by the locus was predominantly driven by a single SNP suggesting the genetic architecture of this trait includes multiple
loci with simple, non-clustered alleles and a locus with potentially more complex alleles. This highlights the diversity of genetic
architectures that can exist for fitness-related traits. Furthermore, this study provides a useful multi-SNP framework for future work
using sequencing data to characterize genetic variation underlying phenotypes in wild populations.
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Bertolotti, Alicia C.; Layer, Ryan M.; Gundappa, Manu Kumar; Gallagher, Michael D.; Pehlivanoglu, Ege & Nome, Torfinn
[Vis alle 23 forfattere av denne artikkelen]
(2020).
The structural variation landscape in 492 Atlantic
salmon genomes.
Nature Communications.
ISSN 2041-1723.
11.
doi:
10.1038/s41467-020-18972-x.
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Structural variants (SVs) are a major source of genetic and phenotypic variation, but remain
challenging to accurately type and are hence poorly characterized in most species. We
present an approach for reliable SV discovery in non-model species using whole genome
sequencing and report 15,483 high-confidence SVs in 492 Atlantic salmon (Salmo salar L.)
sampled from a broad phylogeographic distribution. These SVs recover population genetic
structure with high resolution, include an active DNA transposon, widely affect functional
features, and overlap more duplicated genes retained from an ancestral salmonid autotetraploidization event than expected. Changes in SV allele frequency between wild and
farmed fish indicate polygenic selection on behavioural traits during domestication,
targeting brain-expressed synaptic networks linked to neurological disorders in humans.
This study offers novel insights into the role of SVs in genome evolution and the genetic
architecture of domestication traits, along with resources supporting reliable SV discovery
in non-model species.
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Mulugeta, Teshome Dagne; Nome, Torfinn; To, Thu-Hien; Gundappa, Manu Kumar; Macqueen, Daniel J. & Våge, Dag Inge
[Vis alle 8 forfattere av denne artikkelen]
(2019).
SalMotifDB: a tool for analyzing putative transcription factor binding sites in salmonid genomes.
BMC Genomics.
ISSN 1471-2164.
20(1).
doi:
10.1186/s12864-019-6051-0.
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BACKGROUND:
Recently developed genome resources in Salmonid fish provides tools for studying the genomics underlying a wide range of properties including life history trait variation in the wild, economically important traits in aquaculture and the evolutionary consequences of whole genome duplications. Although genome assemblies now exist for a number of salmonid species, the lack of regulatory annotations are holding back our mechanistic understanding of how genetic variation in non-coding regulatory regions affect gene expression and the downstream phenotypic effects.
RESULTS:
We present SalMotifDB, a database and associated web and R interface for the analysis of transcription factors (TFs) and their cis-regulatory binding sites in five salmonid genomes. SalMotifDB integrates TF-binding site information for 3072 non-redundant DNA patterns (motifs) assembled from a large number of metazoan motif databases. Through motif matching and TF prediction, we have used these multi-species databases to construct putative regulatory networks in salmonid species. The utility of SalMotifDB is demonstrated by showing that key lipid metabolism regulators are predicted to regulate a set of genes affected by different lipid and fatty acid content in the feed, and by showing that our motif database explains a significant proportion of gene expression divergence in gene duplicates originating from the salmonid specific whole genome duplication.
CONCLUSIONS:
SalMotifDB is an effective tool for analyzing transcription factors, their binding sites and the resulting gene regulatory networks in salmonid species, and will be an important tool for gaining a better mechanistic understanding of gene regulation and the associated phenotypes in salmonids. SalMotifDB is available at https://salmobase.org/apps/SalMotifDB .
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Olsen, Hanne Gro; Knutsen, Tim Martin; Kohler, Achim; Svendsen, Morten; Gidskehaug, Lars Halvor & Grove, Harald
[Vis alle 12 forfattere av denne artikkelen]
(2017).
Genome-wide association mapping for milk fat composition and fine mapping of a QTL for de novo synthesis of milk fatty acids on bovine chromosome 13.
Genetics Selection Evolution.
ISSN 0999-193X.
49:20,
s. 1–13.
doi:
10.1186/s12711-017-0294-5.
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Background
Bovine milk is widely regarded as a nutritious food source for humans, although the effects of individual fatty acids on human health is a subject of debate. Based on the assumption that genomic selection offers potential to improve milk fat composition, there is strong interest to understand more about the genetic factors that influence the biosynthesis of bovine milk and the molecular mechanisms that regulate milk fat synthesis and secretion. For this reason, the work reported here aimed at identifying genetic variants that affect milk fatty acid composition in Norwegian Red cattle. Milk fatty acid composition was predicted from the nation-wide recording scheme using Fourier transform infrared spectroscopy data and applied to estimate heritabilities for 36 individual and combined fatty acid traits. The recordings were used to generate daughter yield deviations that were first applied in a genome-wide association (GWAS) study with 17,343 markers to identify quantitative trait loci (QTL) affecting fatty acid composition, and next on high-density and sequence-level datasets to fine-map the most significant QTL on BTA13 (BTA for Bos taurus chromosome).
Results
The initial GWAS revealed 200 significant associations, with the strongest signals on BTA1, 13 and 15. The BTA13 QTL highlighted a strong functional candidate gene for de novo synthesis of short- and medium-chained saturated fatty acids; acyl-CoA synthetase short-chain family member 2. However, subsequent fine-mapping using single nucleotide polymorphisms (SNPs) from a high-density chip and variants detected by resequencing showed that the effect was more likely caused by a second nearby gene; nuclear receptor coactivator 6 (NCOA6). These findings were confirmed with results from haplotype studies. NCOA6 is a nuclear receptor that interacts with transcription factors such as PPARγ, which is a major regulator of bovine milk fat synthesis.
Conclusions
An initial GWAS revealed a highly significant QTL for de novo-synthesized fatty acids on BTA13 and was followed by fine-mapping of the QTL within NCOA6. The most significant SNPs were either synonymous or situated in introns; more research is needed to uncover the underlying causal DNA variation(s).
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Lorenz, Susanne; Barøy, Tale; Sun, Jinchang; Nome, Torfinn; Vodak, Daniel & Bryne, Jan Christian
[Vis alle 21 forfattere av denne artikkelen]
(2016).
Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations.
OncoTarget.
ISSN 1949-2553.
7(5),
s. 5273–5288.
doi:
10.18632/oncotarget.6567.
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In contrast to many other sarcoma subtypes, the chaotic karyotypes of osteosarcoma have precluded the identification of pathognomonic translocations. We here report hundreds of genomic rearrangements in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fused transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which was further supported by typical trans-splicing characteristics. By combining genomic and transcriptomic analysis, certain recurrent rearrangements were identified and further validated in patient biopsies, including a PMP22-ELOVL5 gene fusion, genomic structural variations affecting RB1, MTAP/CDKN2A and MDM2, and, most frequently, rearrangements involving TP53. Most cell lines (7/11) and a large fraction of tumor samples (10/25) showed TP53 rearrangements, in addition to somatic point mutations (6 patient samples, 1 cell line) and MDM2 amplifications (2 patient samples, 2 cell lines). The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors. Although rampant rearrangements appear to be a phenotype of osteosarcomas, we demonstrate that among the huge number of probable passenger rearrangements, specific recurrent, possibly oncogenic, events are present. For the first time the genomic chaos of osteosarcoma is characterized so thoroughly and delivered new insights in mechanisms involved in osteosarcoma development and may contribute to new diagnostic and therapeutic strategies.
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Barson, Nicola; Aykanat, Tutku; Hindar, Kjetil; Baranski, Matthew; Bolstad, Geir Hysing & Fiske, Peder
[Vis alle 22 forfattere av denne artikkelen]
(2015).
Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon.
Nature.
ISSN 0028-0836.
528(7582),
s. 405–408.
doi:
10.1038/nature16062.
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Bruun, Jarle; Kolberg, Matthias; Ahlquist, Terje Cruickshank; Røyrvik, Ellen Christine; Nome, Torfinn & Leithe, Edward
[Vis alle 18 forfattere av denne artikkelen]
(2015).
Regulator of chromosome condensation 2 identifies high-risk patients within both major phenotypes of colorectal cancer.
Clinical Cancer Research.
ISSN 1078-0432.
21(16),
s. 3759–3770.
doi:
10.1158/1078-0432.CCR-14-3294.
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Løvf, Marthe; Nome, Torfinn; Bruun, Jarle; Eknæs, Mette; Bakken, Anne Cathrine & Mpindi, John-Patrick
[Vis alle 12 forfattere av denne artikkelen]
(2014).
A novel transcript, VNN1-AB, as a biomarker for colorectal cancer.
International Journal of Cancer.
ISSN 0020-7136.
135(9),
s. 2077–2084.
doi:
10.1002/ijc.28855.
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Nome, Torfinn; Hoff, Andreas Midbøe; Bakken, Anne Cathrine; Rognum, Torleiv Ole; Nesbakken, Arild & Skotheim, Rolf Inge
(2014).
High frequency of fusion transcripts involving TCF7L2 in colorectal cancer: Novel fusion partner and splice variants.
PLOS ONE.
ISSN 1932-6203.
9(3).
doi:
10.1371/journal.pone.0091264.
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Nyquist, Kaja Beate; Panagopoulos, Ioannis; Thorsen, Jim; Haugom, Lisbeth; Gorunova, Ludmila & Bjerkehagen, Bodil
[Vis alle 13 forfattere av denne artikkelen]
(2012).
Whole-Transcriptome Sequencing Identifies Novel IRF2BP2-CDX1 Fusion Gene Brought about by Translocation t(1;5)(q42;q32) in Mesenchymal Chondrosarcoma.
PLOS ONE.
ISSN 1932-6203.
7(11).
doi:
10.1371/journal.pone.0049705.
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Grindflek, Eli; Meuwissen, Theodorus; Aasmundstad, T.; Hamland, Hanne; Hansen, Marianne H S & Nome, Torfinn
[Vis alle 9 forfattere av denne artikkelen]
(2011).
Revealing genetic relationships between compounds affecting boar taint and reproduction in pigs.
Journal of Animal Science.
ISSN 0021-8812.
89(3),
s. 680–692.
doi:
10.2527/jas.2010-3290.
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Olsen, Hanne Gro; Hayes, Ben J.; Kent, Matthew Peter; Nome, Torfinn; Svendsen, Morten & Larsgaard, Anne-Guro
[Vis alle 7 forfattere av denne artikkelen]
(2011).
Genome-wide association mapping in Norwegian Red cattle identifies quantitative trait loci for fertility and milk production on BTA12.
Animal Genetics.
ISSN 0268-9146.
42(5),
s. 466–474.
doi:
10.1111/j.1365-2052.2011.02179.x.
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Olsen, Hanne Gro; Hayes, Ben J.; Kent, Matthew Peter; Nome, Torfinn; Svendsen, Morten & Lien, Sigbjørn
(2010).
A genome wide association study for QTL affecting direct and maternal effects of stillbirth and dystocia in cattle.
Animal Genetics.
ISSN 0268-9146.
41(3),
s. 273–280.
doi:
10.1111/j.1365-2052.2009.01998.x.
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Dystocia and stillbirth are significant causes of female and neonatal death in many species and there is evidence for a genetic component to both traits. Identifying causal mutations affecting these traits through genome wide association studies could reveal the genetic pathways involved and will be a step towards targeted interventions. Norwegian Red cattle are an ideal model breed for such studies as very large numbers of records are available. We conducted a genome wide association study for direct and maternal effects of dystocia and stillbirth using almost 1 million records of these traits. Genotyping costs were minimized by genotyping the sires of the recorded cows, and using daughter averages as phenotypes. A dense marker map containing 17 343 single nucleotide polymorphisms covering all autosomal chromosomes was utilized. The genotyped sires were assigned to one of two groups in an attempt to ensure independence between the groups. Associations were only considered validated if they occurred in both groups. Strong associations were found and validated on chromosomes 4, 5, 6, 9, 12, 20, 22 and 28. The QTL region on chromosome 6 was refined using LDLA analysis. The results showed that this chromosome most probably contains two QTL for direct effect on dystocia and one for direct effect on stillbirth. Several candidate genes may be identified close to these QTL. Of these, a cluster of genes expected to affect bone and cartilage formation (i.e. SPP1, IBSP and MEPE) are of particular interest and we suggest that these genes are screened in candidate gene studies for dystocia and stillbirth in cattle as well as other species.
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Nilsen, Heidi; Olsen, Hanne Gro; Hayes, Ben J.; Nome, Torfinn; Sehested, Erling & Svendsen, Morten
[Vis alle 8 forfattere av denne artikkelen]
(2009).
Characterization of a QTL region affecting clinical mastitis and protein yield on BTA6.
Animal Genetics.
ISSN 0268-9146.
40(5),
s. 701–712.
doi:
10.1111/j.1365-2052.2009.01908.x.
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P>Quantitative trait loci affecting clinical mastitis were detected and fine mapped to a narrow region on bovine chromosome 6 in the Norwegian Red cattle population. The region includes the casein gene cluster and several candidate genes thought to influence clinical mastitis. The most significant results were found for SNPs within the Mucin 7 gene. This gene encodes an antimicrobial peptide and constitutes part of the first line of defence for the mucosal immune system. Detection of long haplotypes extending several Mb may indicate that artificial selection has influenced the haplotype structures in the region. A search for selection sweeps supports this observation and coincides with association results found both by single SNP and haplotype analyses. Our analyses identified haplotypes carrying quantitative trait loci alleles associated with high protein yield and simultaneously fewer incidences of clinical mastitis. The fact that such haplotypes are found in relative high frequencies in Norwegian Red may reflect the combined breeding goal that is characterized by selection for both milk production and disease resistance. The identification of these haplotypes raises the possibility of overcoming the unfavourable genetic correlation between these traits through haplotype-assisted selection.
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Nilsen, Heidi; Olsen, Hanne Gro; Hayes, Ben J.; Sehested, Erling; Svendsen, Morten & Nome, Torfinn
[Vis alle 8 forfattere av denne artikkelen]
(2009).
Casein haplotypes and their association with milk production traits in Norwegian Red cattle.
Genetics Selection Evolution.
ISSN 0999-193X.
41(art. 24).
doi:
10.1186/1297-9686-41-24.
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A high resolution SNP map was constructed for the bovine casein region to identify haplotype structures and study associations with milk traits in Norwegian Red cattle. Our analyses suggest separation of the casein cluster into two haplotype blocks, one consisting of the CSN1S1, CSN2 and CSN1S2 genes and another one consisting of the CSN3 gene. Highly significant associations with both protein and milk yield were found for both single SNPs and haplotypes within the CSN1S1-CSN2-CSN1S2 haplotype block. In contrast, no significant association was found for single SNPs or haplotypes within the CSN3 block. Our results point towards CSN2 and CSN1S2 as the most likely loci harbouring the underlying causative DNA variation. In our study, the most significant results were found for the SNP CSN2_67 with the C allele consistently associated with both higher protein and milk yields. CSN2_67 calls a C to an A substitution at codon 67 in beta-casein gene resulting in histidine replacing proline in the amino acid sequence. This polymorphism determines the protein variants A1/B (CSN2_67 A allele) versus A2/A3 (CSN2_67 C allele). Other studies have suggested that a high consumption of A1/B milk may affect human health by increasing the risk of diabetes and heart diseases. Altogether these results argue for an increase in the frequency of the CSN2_67 C allele or haplotypes containing this allele in the Norwegian Red cattle population by selective breeding.
Se alle arbeider i Cristin
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Pearse, Devon E.; Barson, Nicola; Nome, Torfinn; Gao, Guangtu; Campbell, Matthew A. & Abadía-Cardoso, Alicia
[Vis alle 32 forfattere av denne artikkelen]
(2020).
Publisher Correction: Sex-dependent dominance maintains migration supergene in rainbow trout (Nature Ecology & Evolution, (2019), 3, 12, (1731-1742), 10.1038/s41559-019-1044-6).
Nature Ecology and Evolution.
ISSN 2397-334X.
4(1).
doi:
10.1038/s41559-019-1076-y.
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To, Thu-Hien; Grønvold, Lars; Nome, Torfinn; Namouchi, Amine; Våge, Dag Inge & Sandve, Simen Rød
(2019).
A salmonid ohnology pipeline.
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Namouchi, Amine; Nome, Torfinn; To, Thu-Hien; Grønvold, Lars; Sandve, Simen Rød & Våge, Dag Inge
(2019).
SalmoBase2.0: An integrative genomic data resource for salmonids.
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Sandve, Simen Rød; Hvidsten, Torgeir Rhoden; Lien, Sigbjørn; Rori, Rohlfs; Jakobsen, Kjetill Sigurd & Nome, Torfinn
[Vis alle 9 forfattere av denne artikkelen]
(2017).
Evolution after whole genome duplication - insights from the salmonids.
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Nome, Torfinn; Sandve, Simen Rød; Lien, Sigbjørn & Kent, Matthew Peter
(2017).
Development of exome capture sequencing for the Atlantic salmon (Salmo salar).
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Barson, Nicola; Aykanat, Tutku; Hindar, Kjetil; Baranski, Matthew; Bolstad, Geir Hysing & Fiske, Peder
[Vis alle 22 forfattere av denne artikkelen]
(2016).
Sex-Dependent Dominance At A Single Locus Maintains Variation In Age At Maturity In Salmon.
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Publisert
1. mars 2022 15:36
- Sist endret
13. jan. 2023 11:15