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| 2. |
- Huyghe, Jeroen R., et al.
(författare)
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Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait
- 2008
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 83:3, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.
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| 3. |
- Van Laer, Lut, et al.
(författare)
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The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment
- 2008
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 17:2, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Age-related hearing impairment (ARHI) is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. The contribution of various environmental factors has been relatively extensively studied. In contrast, investigations to identify the genetic risk factors have only recently been initiated. In this paper we describe the results of an association study performed on 2418 ARHI samples derived from nine centers from seven European countries. In 70 candidate genes, a total of 768 tag single nucleotide polymorphisms (SNPs) were selected based on HAPMAP data. These genes were chosen among the monogenic hearing loss genes identified in mice and men in addition to several strong functional candidates. After genotyping and data polishing, statistical analysis of all samples combined resulted in a P-value that survived correction for multiple testing for one SNP in the GRHL2 gene. Other SNPs in this gene were also associated, albeit to a lesser degree. Subsequently, an analysis of the most significant GRHL2 SNP was performed separately for each center. The direction of the association was identical in all nine centers. Two centers showed significant associations and a third center showed a trend towards significance. Subsequent fine mapping of this locus demonstrated that the majority of the associated SNPs reside in intron 1. We hypothesize that the causative variant may change the expression levels of a GRHL2 isoform.
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| 4. |
- Risgaard-Petersen, N., et al.
(författare)
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Evidence for complete denitrification in a benthic foraminifer
- 2006
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 443:7107, s. 93-96
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Tidskriftsartikel (refereegranskat)abstract
- Benthic foraminifera are unicellular eukaryotes found abundantly in many types of marine sediments. Many species survive and possibly reproduce in anoxic habitats(1), but sustainable anaerobic metabolism has not been previously described. Here we demonstrate that the foraminifer Globobulimina pseudospinescens accumulates intracellular nitrate stores and that these can be respired to dinitrogen gas. The amounts of nitrate detected are estimated to be sufficient to support respiration for over a month. In a Swedish fjord sediment where G. pseudospinescens is the dominant foraminifer, the intracellular nitrate pool in this species accounted for 20% of the large, cell-bound, nitrate pool present in an oxygen-free zone. Similarly high nitrate concentrations were also detected in foraminifera Nonionella cf. stella and a Stainforthia species, the two dominant benthic taxa occurring within the oxygen minimum zone of the continental shelf off Chile. Given the high abundance of foraminifera in anoxic marine environments(1-3), these new findings suggest that foraminifera may play an important role in global nitrogen cycling and indicate that our understanding of the complexity of the marine nitrogen cycle is far from complete.
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| 5. |
- Konings, A., et al.
(författare)
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Candidate gene association study for noise-induced hearing loss in two independent noise-exposed populations
- 2009
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Ingår i: Annals of Human Genetics. - : Wiley. - 0003-4800 .- 1469-1809. ; 73:2, s. 215-224
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Tidskriftsartikel (refereegranskat)abstract
- Millions of people are daily exposed to high levels of noise. Consequently, noise-induced hearing loss (NIHL) is one of the most important occupational health hazards worldwide. In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. Calculation of odds ratios revealed a significant association of rs588035 with NIHL in the Swedish high noise exposure level group. Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but further replication in independent sample sets is mandatory.
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| 6. |
- Schmid, M. C., et al.
(författare)
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Anaerobic ammonium-oxidizing bacteria in marine environments: widespread occurrence but low diversity
- 2007
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Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 9:6, s. 1476-1484
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory and field studies have indicated that anaerobic ammonium oxidation (anammox) is an important process in the marine nitrogen cycle. In this study 11 additional anoxic marine sediment and water column samples were studied to substantiate this claim. In a combined approach using the molecular methods, polymerase chain reaction (PCR), qualitative and quantitative fluorescence in situ hybridization (FISH), as well as N-15 stable isotope activity measurements, it was shown that anammox bacteria were present and active in all samples investigated. The anammox activity measured in the sediment samples ranged from 0.08 fmol cell(-1) day(-1) N-2 in the Golfo Dulce (Pacific Ocean, Costa Rica) sediment to 0.98 fmol cell(-1) day(-1) N-2 in the Gullmarsfjorden (North Sea, Sweden) sediment. The percentage of anammox cell of the total population (stained with DAPI) as assessed by quantitative FISH was highest in the Barents Sea (9% +/- 4%) and in most of the samples well over 2%. Fluorescence in situ hybridization and phylogenetic analysis of the PCR products derived from the marine samples indicated the exclusive presence of members of the Candidatus 'Scalindua' genus. This study showed the ubiquitous presence of anammox bacteria in anoxic marine ecosystems, supporting previous observations on the importance of anammox for N cycling in marine environments.
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