| 1. |
|
|
| 2. |
|
|
| 3. |
- Rioux, John D., et al.
(författare)
-
Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease
- 2001
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 29:2, s. 223-228
-
Tidskriftsartikel (refereegranskat)abstract
- Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease1. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10−4). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P<2×10−7) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence—each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.
|
|
| 4. |
- Solan, M., et al.
(författare)
-
In situ quantification of bioturbation using time-lapse fluorescent sediment profile imaging (f-SPI), luminophore tracers and model simulation
- 2004
-
Ingår i: Marine Ecology-Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 271, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- In order to link actual biological data on bioturbation to the abstract parameters in bioturbation models, high-resolution data on the frequency and lengths of particle displacements are required. The temporal variation in bioturbation for a subtidal macrofaunal assemblage was studied non-invasively and in situ using an optically modified fluorescence sensitive time-lapse sediment profile imaging camera (f-SPI), fluorescent-dyed sediment particles (luminophores) and mathematical modelling. This combined approach allowed tracer particles to be non-invasively tracked and their displacements monitored at an unprecedented spatial (78 mum) and temporal (every 10 min) resolution for extended periods of time (16 h). The redistribution of luminophores was digitally acquired from sequential images and compared to model predictions, with particle transport modelled as (1) a diffusive process, allowing the biodiffusion coefficient, D-b, to be estimated, and (2) a non-local process, allowing a reworking activity constant, a, to be calculated. Model predictions of luminophore particle transport for the final image of the f-SPI sequence gave: D-b = 1.26 x 10(2) cm(2) yr(-1); a = 5.23 x 10(-2) cm(-1) yr(-1). Discrete values of a fluctuated widely throughout the sequence and allowed discrete bioturbation events to be identified. Time-lapse movie sequences revealed that most of the bioturbation observed during the deployment could be directly attributed to the behaviour of the brachyuran crab Hyas araneus. Our findings demonstrate that f-SPI provides a rapid and non-invasive means to visualise and quantify, in situ, the extent and influence of discrete infaunal bioturbation events on particle mixing. This technique provides detailed information on the spatial and temporal resolution of such bioturbation events, which could significantly improve existing models of bioturbation.
|
|
