| 1. |
- Nordström, Karl J. V., et al.
(författare)
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Comprehensive comparisons of the current human, mouse, and rat RefSeq, Ensembl, EST, and FANTOM3 datasets : identification of new human genes with specific tissue expression profile
- 2006
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 348:3, s. 1063-1074
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of functional genetic elements in the genomes is continuously growing and new entries are entered in various databases on a regular basis. We have here merged the genetic elements in RefSeq, Ensembl, FANTOM3, HINV, and NCBI:s ESTdb using the genome assemblies in order to achieve a comprehensive picture of the current status of the identity and gene number in human, mouse, and rat. The number of human protein coding genes has not increased (25,043) while the increased sequencing of mouse transcripts has provided the considerably higher number of protein coding genes (31,578) in mouse. The results indicate large discrepancies between the datasets, as considerable numbers of unique transcripts can be found in each dataset. Despite the high number of ncRNA (38 129 in mouse) there are also almost 20,000 EST clusters in both mouse and humans with more than one EST that do not overlap any transcript suggesting that several new genetic elements are still to be found. We also demonstrated presence of new genes by identifying new human ones that have specific tissue profiles, using RT-PCR on rat tissues.
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| 2. |
- Bjarnadóttir, Thóra K., et al.
(författare)
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Identification of novel splice variants of Adhesion G protein-coupled receptors
- 2007
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Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 387:1-2, s. 38-48
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Tidskriftsartikel (refereegranskat)abstract
- Alternative splicing is an important mechanism to generate proteome diversity in higher eukaryotic organisms. We searched for splice variants of the human Adhesion family of G protein-coupled receptors (GPCRs) using mRNA sequences and expressed sequence tags. The results presented here describe 53 human splice variants among the 33 Adhesion GPCRs. Many of these variants appear to be coding for “functional” proteins (29) while the others are seemingly “non-functional” (24). Novel functional splice variants were found for: CD97, CELR3, EMR2, EMR3, GPR56, GPR110, GPR112–GPR114, GPR116, GPR123–GPR126, GPR133, HE6, and LEC1–LEC3. Splice variants for GPR116, GPR125, GPR126, and HE6 were found conserved in other species. Several of the functional splice variants lack one or more of the functional domains that are found in the N-termini of these receptors. These functional domains are likely to affect ligand binding or interaction with other proteins and these novel splice variants may have important roles for the specificity of interactions between these receptors and extracellular molecules. Another type of splice variants found here lacks a GPCR proteolytic site (GPS). The GPS domain has been shown to be essential for the proteolytic cleavage of the receptors N-termini and for cellular surface expression. We suggest that these alternative splice variants may be crucial for the function of the receptors while the seemingly non-functional splice variants may be a part of a regulative mechanism.
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| 3. |
- Mirza, Majd A I, et al.
(författare)
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Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 205:2, s. 385-390
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Subjects with chronic kidney disease (CKD) are at higher risk for cardiovascular (CV) disease than the general population. These patients have elevated circulating levels of FGF23, which predict for increased mortality in CKD patients on hemodialysis. Since CV disease is a major cause of death in CKD, we investigated the association between FGF23 and vascular function. METHODS AND RESULTS: We employed a community-based cohort of subjects aged 70, the PIVUS study (n=967), to investigate the relation between serum FGF23, endothelium function and arterial stiffness. Higher FGF23 was weakly associated with both impaired endothelium-dependent (beta=-0.08, p<0.05) and endothelium-independent (beta=-0.08, p<0.01) vasodilation. The association was stronger in subjects with eGFR> or =90mL/min/1.73m(2) (beta=-0.19 and beta=-0.22, respectively, p<0.001). In addition, higher FGF23 was associated with increased arterial stiffness exclusively in subjects with an age-adjusted impaired renal function (eGFR<60mL/min/1.73m(2)) (beta=0.26, p<0.001). All associations were independent of gender, biochemical covariates and established CV risk factors. CONCLUSIONS: Higher serum FGF23 levels, even within the normal range, are independently associated with impaired vasoreactivity and increased arterial stiffness in the community. Additional studies are required to determine possible direct vascular effects of FGF23 and whether FGF23 is a modifiable CV risk factor.
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| 4. |
- Mirza, Majd A I, et al.
(författare)
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Relationship between circulating FGF23 and total body atherosclerosis in the community
- 2009
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 24:10, s. 3125-3131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fibroblast growth factor-23 (FGF23) is a regulator of mineral metabolism and has been suggested to play a role in vascular calcification in chronic kidney disease (CKD). Data on the association between FGF23 and atherosclerosis, both in CKD and in the community, is limited. METHODS: The total body atherosclerosis score (AS) was determined by a magnetic resonance imaging-based angiography in 306 elderly men and women, representing a subsample of the community-based PIVUS cohort. Subjects were divided into three categories based on AS: AS = 0, low AS and high AS. Serum FGF23 was measured using a two-site monoclonal antibody ELISA. RESULTS: In continuous and multi-category regression models, higher FGF23 was associated with a significant increase in the odds of having a high AS (OR 1.43, CI 1.06-1.92 to OR 3.01, CI 1.52-5.99). This association was stronger in individuals with eGFR <60 mL/min/1.73 m(2) (n = 27), reaching a nearly 6-fold increase in the odds for a high AS in the upper FGF23 tertile (OR 5.64, CI 2.78-11.5). We found weaker support for a relationship between FGF23 and the presence of atherosclerosis as subjects in the highest FGF23 tertile had an increased risk for an AS > 0 in crude models (OR 1.93, CI 1.05-3.55), but this was not statistically significant in adjusted (OR 1.42, CI 0.74-1.72) models. CONCLUSIONS: We provide novel evidence supporting an association between serum FGF23 and total body atherosclerosis in the community. Additional studies are warranted to determine the prospective relationship between FGF23 and atherosclerosis, and whether FGF23 is a modifiable cardiovascular risk factor.
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| 5. |
- Mirza, Majd A. I., et al.
(författare)
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Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 207:2, s. 546-551
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Tidskriftsartikel (refereegranskat)abstract
- Fibroblast growth factor-23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Serum FGF23 is elevated in chronic kidney disease (CKD) and is a prognostic marker of poor outcomes, such as faster CKD progression and increased mortality in hemodialysis patients. Despite the high prevalence of cardiovascular disease in CKD, the relation between circulating FGF23 and cardiovascular risk factors, both in CKD and in the community, has not been studied in detail. We evaluated the relation between FGF23, left ventricular mass index (LVMI), hypertrophy (LVH) and LV geometry, employing the community-based PIVUS cohort. In total, 795 Swedish men and women aged 70 were included of which 164 had an age-adjusted diminished renal function (estimated glomerular filtration rate<60mL/min/1.73m(2)). FGF23 was positively associated with LVMI (beta=0.11, CI 0.01-0.18), with increased odds for the presence of LVH (OR 1.28, CI 1.09-1.51) and for concentric hypertrophy (OR 1.45, CI 1.19-1.77) in the whole population. All associations were stronger in subjects with eGFR<60mL/min/1.73m(2) (beta=0.30, CI 0.15-0.46 for LVMI; OR 1.86, CI 1.30-2.67 for the presence of LVH; OR 1.83, CI 1.17-2.85 and OR 1.87, CI 1.08-3.22 for concentric and eccentric hypertrophy, respectively). The results were essentially unaltered in multivariate models. In summary, elevated serum FGF23 levels, even within the normal range, are associated with increased LVMI and increased risk for the presence of LVH in elderly subjects. Additional longitudinal studies that evaluate the predictive power of FGF23 and whether FGF23 has additional clinical applications are needed.
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| 6. |
- Nordström, Karl J V, et al.
(författare)
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Critical evaluation of the FANTOM3 non-coding RNA transcripts
- 2009
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 94:3, s. 169-176
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Tidskriftsartikel (refereegranskat)abstract
- We studied the genomic positions of 38,129 putative ncRNAs from the RIKEN dataset in relation to protein-coding genes. We found that the dataset has 41% sense, 6% antisense, 24% intronic and 29% intergenic transcripts. Interestingly, 17,678 (47%) of the FANTOM3 transcripts were found to potentially be internally primed from longer transcripts. The highest fraction of these transcripts was found among the intronic transcripts and as many as 77% or 6929 intronic transcripts were both internally primed and unspliced. We defined a filtered subset of 8535 transcripts that did not overlap with protein-coding genes, did not contain ORFs longer than 100 residues and were not internally primed. This dataset contains 53% of the FANTOM3 transcripts associated to known ncRNA in RNAdb and expands previous similar efforts with 6523 novel transcripts. This bioinformatic filtering of the FANTOM3 non-coding dataset has generated a lead dataset of transcripts without signs of being artefacts, providing a suitable dataset for investigation with hybridization-based techniques.
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