| 1. |
- Almén, Markus Sällman, et al.
(författare)
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Genome wide analysis reveals association of a FTO gene variant with epigenetic changes
- 2012
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 99:3, s. 132-137
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Tidskriftsartikel (refereegranskat)abstract
- Variants of the FTO gene show strong association with obesity, but the mechanisms behind this association remain unclear. We determined the genome wide DNA methylation profile in blood from 47 female preadolescents. We identified sites associated with the genes KARS, TERF2IP, DEXI, MSI1,STON1 and BCAS3 that had a significant differential methylation level in the carriers of the FTO risk allele (rs9939609). In addition, we identified 20 differentially methylated sites associated with obesity. Our findings suggest that the effect of the FTO obesity risk allele may be mediated through epigenetic changes. Further, these sites might prove to be valuable biomarkers for the understanding of obesity and its comorbidites.
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| 2. |
- Behboudi, A, et al.
(författare)
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Functional significance of absence : The chromosomal segment harboring the Tp53 gene is missing in the T55 rat radiation hybrid mapping panel
- 2002
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Ingår i: Genomics. - : Academic Press. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-848
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2–6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 3. |
- Behboudi, Afrouz, 1967, et al.
(författare)
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The functional significance of absence: the chromosomal segment harboring Tp53 is absent from the T55 rat radiation hybrid mapping panel.
- 2002
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-8
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2-6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 4. |
- Biermann, Jana, et al.
(författare)
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A 17-marker panel for global genomic instability in breast cancer.
- 2020
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 112:2, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- Genomic instability is a hallmark of cancer that plays a pivotal role in breast cancer development and evolution. A number of existing prognostic gene expression signatures for breast cancer are based on proliferation-related genes. Here, we identified a 17-marker panel associated with genome stability. A total of 136 primary breast carcinomas were stratified by genome stability. Matched gene expression profiles showed an innate segregation based on genome stability. We identified a 17-marker panel stratifying the training and validation cohorts into high- and low-risk patients. The 17 genes associated with genomic instability strongly impacted clinical outcome in breast cancer. Pathway analyses determined chromosome organisation, cell cycle regulation, and RNA processing as the underlying biological processes, thereby offering options for drug development and treatment tailoring. Our work supports the applicability of the 17-marker panel to improve clinical outcome prediction for breast cancer patients based on a signature accounting for genomic instability.
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| 5. |
- Bjarnadóttir, Thóra K., et al.
(författare)
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Comprehensive repertoire and phylogenetic analysis of the G-protein-coupled receptors in human and mouse
- 2006
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 88:3, s. 263-273
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Tidskriftsartikel (refereegranskat)abstract
- Understanding differences in the repertoire of orthologous gene pairs is vital for interpretation of pharmacological and physiological experiments if conclusions are conveyed between species. Here we present a comprehensive dataset for G protein-coupled receptors (GPCRs) in both human and mouse with a phylogenetic road map. We performed systematic searches applying several search tools such as BLAST, BLAT, and Hidden Markov models and searches in literature data. We aimed to gather a full-length version of each human or mouse GPCR in only one copy referring to a single chromosomal position. Moreover, we performed detailed phylogenetic analysis of the transmembrane regions of the receptors to establish accurate orthologous pairs. The results show the identity of 495 mouse and 400 human functional nonolfactory GPCRs. Overall, 329 of the receptors are found in one-to-one orthologous pairs, while 119 mouse and 31 human receptors originate from species-specific expansions or deletions. The average percentage similarity of the orthologue pairs is 85%, while it varies between the main GRAFS families from an average of 59 to 94%. The orthologous pairs for the lipid-binding GPCRs had the lowest levels of conservation, while the biogenic amines had highest levels of conservation. Moreover, we searched for expressed sequence tags (ESTs) and identified more than 17,000 ESTs matching GPCRs in mouse and human, providing information about their expression patterns. On the whole, this is the most comprehensive study of the gene repertoire that codes for human and mouse GPCRs. The datasets are available for downloading.
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| 6. |
- Bjarnadóttir, Thóra K., et al.
(författare)
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The human and mouse repertoire of the adhesion family of G-protein-coupled receptors
- 2004
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 84:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- The adhesion G-protein-coupled receptors (GPCRs) (also termed LN-7TM or EGF-7TM receptors) are membrane-bound proteins with long N-termini containing multiple domains. Here, 2 new human adhesion-GPCRs, termed GPR133 and GPR144, have been found by searches done in the human genome databases. Both GPR133 and GPR144 have a GPS domain in their N-termini, while GPR144 also has a pentraxin domain. The phylogenetic analyses of the 2 new human receptors show that they group together without close relationship to the other adhesion-GPCRs. In addition to the human genes, mouse orthologues to those 2 and 15 other mouse orthologues to human were identified (GPR110, GPR111, GPR112, GPR113, GPR114, GPR115, GPR116, GPR123, GPR124, GPR125, GPR126, GPR128, LEC1, LEC2, and LEC3). Currently the total number of human adhesion-GPCRs is 33. The mouse and human sequences show a clear one-to-one relationship, with the exception of EMR2 and EMR3, which do not seem to have orthologues in mouse. EST expression charts for the entire repertoire of adhesion-GPCRs in human and mouse were established. Over 1600 ESTs were found for these receptors, showing widespread distribution in both central and peripheral tissues. The expression patterns are highly variable between different receptors, indicating that they participate in a number of physiological processes.
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| 7. |
- Cavalli, Marco, et al.
(författare)
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Allele-specific transcription factor binding in liver and cervix cells unveils many likely drivers of GWAS signals
- 2016
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 107:6, s. 248-254
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) point to regions with associated genetic variants but rarely to a specific gene and therefore detailed knowledge regarding the genes contributing to complex traits and diseases remains elusive. The functional role of GWAS-SNPs is also affected by linkage disequilibrium with many variants on the same haplotype and sometimes in the same regulatory element almost equally likely to mediate the effect. Using ChIP-seq data on many transcription factors, we pinpointed genetic variants in HepG2 and HeLa-S3 cell lines which show a genome-wide significant difference in binding between alleles. We identified a collection of 3713 candidate functional regulatory variants many of which are likely drivers of GWAS signals or genetic difference in expression. A recent study investigated many variants before finding the functional ones at the GALNT2 locus, which we found in our genome-wide screen in HepG2. This illustrates the efficiency of our approach.
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| 8. |
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| 9. |
- Chattopadhyay, Balaji, et al.
(författare)
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Novel genome reveals susceptibility of popular gamebird, the red-legged partridge (Alectoris rufa, Phasianidae), to climate change
- 2021
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646.
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Tidskriftsartikel (refereegranskat)abstract
- We produced a high-quality de novo genome assembly of the red-legged partridge A. rufa, the first reference genome of its genus, by utilising novel 10× Chromium technology. The estimated genome size was 1.19 Gb with an overall genome heterozygosity of 0.0022; no runs of homozygosity were observed. In total, 21,589 protein coding genes were identified and assigned to 16,772 orthologs. Of these, 201 emerged as unique to Alectoris and were enriched for positive regulation of epithelial cell migration, viral genome integration and maturation. Using PSMC analysis, we inferred a major demographic decline commencing ~140,000 years ago, consistent with forest expansion and reduction of open habitats during the Eemian interglacial. Present-day populations exhibit the historically lowest genetic diversity. Besides implications for management and conservation, this genome also promises key insights into the physiology of these birds with a view to improving poultry husbandry practices.
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| 10. |
- Courseaux, A, et al.
(författare)
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Definition of the minimal MEN 1 candidate area based on a 5-Mb integrated map proximal to 11q13 : The european consortium on men1
- 1996
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 37:3, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.
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