| 1. |
|
|
| 2. |
|
|
| 3. |
- Hollis, J. A., et al.
(författare)
-
Detrital zircon U-Pb-Hf and O isotope character of the Cahill Formation and Nourlangie Schist, Pine Creek Orogen: Implications for the tectonic correlation and evolution of the North Australian Craton
- 2014
-
Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268. ; 246, s. 35-53
-
Tidskriftsartikel (refereegranskat)abstract
- Detrital zircon age and Hf isotope patterns for the Cahill Formation and Nourlangie Schist are distinctly different from other Paleoproterozoic successions in the North Australian Craton. The Cahill Formation and Nourlangie Schist comprise the bulk of the Paleoproterozoic strata in the Nimbuwah Domain, the easternmost part of the Pine Creek Orogen on the northern margin of the North Australian Craton. They comprise micaceous and quartzofeldspathic schist, carbonaceous schist, calc-silicate rock, amphibolite and quartzite, deformed and metamorphosed during emplacement of the granitic to dioritic Nimbuwah Complex at 1867-1857 Ma. The Cahill Formation hosts several world-class uranium deposits including Ranger, Jabiluka and Nabarlek. U-Pb SHRIMP and LA-SF-ICPMS detrital zircon spectra for four samples of the Cahill Formation and six samples of the Nourlangie Schist show a similar broad spectrum of ages mainly in the range 3300-1900 Ma. A ubiquitous dominant peak at 2530-2470 Ma matches the age of underlying Neoarchean basement, but is distinct in its dominantly mantle-like Hf and O zircon isotopic character, which shows closer similarity with possible source rocks from the Gawler Craton or alternatively from the Dharwar Craton. Common smaller age peaks occur at 2180 Ma, 2080 Ma and 2020 Ma. The first two have no known magmatic age correlatives in the North Australian Craton. Zircons of the 2020 Ma peak have distinctively unradiogenic Hf and elevated delta O-18, at variance with local rocks of this age but similar to detrital zircon of the same age from the Gawler Craton. In contrast to younger Proterozoic sedimentary successions within the Pine Creek Orogen, which contain ubiquitous ca. 1870 Ma detritus, the detrital spectra for the Cahill Formation and Nourlangie Schist contain almost no ca. 1870 Ma detritus. A maximum deposition age of ca. 1866 Ma indicates deposition within error of intrusion of the Nimbuwah Complex. We propose that the Cahill Formation and Nourlangie Schist were deposited at a plate margin immediately prior to convergent tectonism. This resulted in their burial, deformation and amphibolite facies metamorphism during orogenesis associated with the Nimbuwah Event. These findings have implications for understanding the Paleoproterozoic evolution of the Pine Creek Orogen within the context of northern Australia. Crown Copyright (C) 2014 Published by Elsevier B.V. All rights reserved.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Bogaert, Elke, et al.
(författare)
-
Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis
- 2012
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 33:2, s. 418-420
-
Tidskriftsartikel (refereegranskat)abstract
- Excitotoxicity is thought to play a pathogenic role in amyotrophic lateral sclerosis (ALS). Excitotoxic motor neuron death is mediated through the Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type of glutamate receptors and Ca(2+) permeability is determined by the GluR2 subunit. We investigated whether polymorphisms or mutations in the GluR2 gene (GRIA2) predispose patients to ALS. Upon sequencing 24 patients and 24 controls no nonsynonymous coding variants were observed but 24 polymorphisms were identified, 9 of which were novel. In a screening set of 310 Belgian ALS cases and 794 healthy controls and a replication set of 3157 cases and 5397 controls from 6 additional populations no association with susceptibility, age at onset, or disease duration was observed. We conclude that polymorphisms in the GluR2 gene (GRIA2) are not a major contributory factor in the pathogenesis of ALS.
|
|
| 7. |
- C. Lin, Yin, et al.
(författare)
-
A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate
- 2010
-
Ingår i: Nature Immunology. - : Nature Publishing Group. - 1529-2908 .- 1529-2916. ; 11:7, s. 635-U109
-
Tidskriftsartikel (refereegranskat)abstract
- It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.
|
|
| 8. |
- Fogh, Isabella, et al.
(författare)
-
A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis
- 2014
-
Ingår i: Human Molecular Genetics. - Oxford : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:8, s. 2220-2231
-
Tidskriftsartikel (refereegranskat)abstract
- Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (90) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P 1.11 10(8); OR 0.82) that was validated when combined with genotype data from a replication cohort (P 8.62 10(9); OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P 7.69 10(9); OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as 12 using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.
|
|
| 9. |
- Glass, Daniel, et al.
(författare)
-
Gene expression changes with age in skin, adipose tissue, blood and brain.
- 2013
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age.RESULTS: Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues.CONCLUSIONS: Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.
|
|
| 10. |
- Parts, Leopold, et al.
(författare)
-
Extent, causes, and consequences of small RNA expression variation in human adipose tissue.
- 2012
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:5
-
Tidskriftsartikel (refereegranskat)abstract
- Small RNAs are functional molecules that modulate mRNA transcripts and have been implicated in the aetiology of several common diseases. However, little is known about the extent of their variability within the human population. Here, we characterise the extent, causes, and effects of naturally occurring variation in expression and sequence of small RNAs from adipose tissue in relation to genotype, gene expression, and metabolic traits in the MuTHER reference cohort. We profiled the expression of 15 to 30 base pair RNA molecules in subcutaneous adipose tissue from 131 individuals using high-throughput sequencing, and quantified levels of 591 microRNAs and small nucleolar RNAs. We identified three genetic variants and three RNA editing events. Highly expressed small RNAs are more conserved within mammals than average, as are those with highly variable expression. We identified 14 genetic loci significantly associated with nearby small RNA expression levels, seven of which also regulate an mRNA transcript level in the same region. In addition, these loci are enriched for variants significant in genome-wide association studies for body mass index. Contrary to expectation, we found no evidence for negative correlation between expression level of a microRNA and its target mRNAs. Trunk fat mass, body mass index, and fasting insulin were associated with more than twenty small RNA expression levels each, while fasting glucose had no significant associations. This study highlights the similar genetic complexity and shared genetic control of small RNA and mRNA transcripts, and gives a quantitative picture of small RNA expression variation in the human population.
|
|
