Search

Although HLA-DQ genes are the major celiac disease (CD) susceptibility genes, results from Finnish families suggest that not all DQ2-encoding haplotypes confer equal susceptibility to CD, implying the effect of other gene(s) in the HLA region. The aim of the present work was to extend and confirm the aforementioned results in a southern European population ( Italian) and to better localize the additional risk factor/s. The association of nine loci spanning the HLA region from DR to HFE, 4.5-Mb telomeric of HLA-A, was tested. The analysis was performed by comparing marker frequencies in DR3-DQ2 haplotypes transmitted and non-transmitted to the affected offspring in 156 Italian CD families selected for having at least one DR3-positive parent. The same analysis was performed independently in 101 Finnish CD families selected with the same criteria. Three alleles, MICA-A5.1, MICB-CA24 and MIB-350, all characteristic of the B8-DR3 extended haplotype, showed a significantly increased frequency in DR3 transmitted haplotypes in the Italian families. DR3 haplotypes carrying the combination of these alleles conferred an approximate fourfold increased CD risk. B8-DR3 transmitted haplotypes were significantly more conserved telomerically down to the MIC-Class I region. Similar results were seen in the Finnish families. The major conclusion that holds true in both populations is that, while DQ2 is an absolute requirement for the development of CD, the presence of an additional genetic factor within the MIC-Class I region confers an approximate 4-fold increased risk of the disease. [ABSTRACT FROM AUTHOR]

Background: HLA-DQ is the only established susceptibility factor for coeliac disease. We tested whether all HLA haplotypes with the known risk marker, HLA-DQ2, confer equal susceptibility to coeliac disease, i.e. whether haplotype transmission from DQ2 homozygous parents to patients is random. The random transmission would strengthen the importance of DQ2 as the only risk factor within the HLA region. Methods: Inheritance of DQ2-positive haplotypes from parent to patients was investigated in 14 of 127 Finnish coeliac families who had an HLA-DQ2 homozygous parent. HLA alleles and 18 HLA-linked microsatellite markers were used to determine the haplotypes, which were divided into those transmitted and those non-transmitted from DQ2-homozygous parents to patients. Results: Transmitted haplotypes differed clearly from those not transmitted. The alleles in the transmitted haplotypes were strongly conserved and predominantly consisted of the well-known HLA-A*01, B*08, DRB1*03, DQ2, DPB1*0101 haplotype. The non-transmitted haplotypes, on the other hand, were significantly more heterogeneous; in particular, markers near HLA-A and-B genes differed from the transmitted haplotypes. Conclusions: The results suggest that DQ2 is not the only HLA-linked genetic risk factor for coeliac disease but the conserved haplotype harbours at least one other risk gene. [ABSTRACT FROM AUTHOR]

The Finnish population is genetically relatively homogeneous and has a narrow gene pool as a result of founder effect followed by rapid population growth. We here demonstrate that microsatellite markers are highly informative tools for major histocompatibility complex (MHC) analysis in this population. First, no variation in 12 MHC-linked microsatellites could be observed in certain CYP21-deficient chromosomes, which as a result of founder effect most likely derived from common ancestors. Second, amongst 131 Finnish chromosomes, some, but not all, apparently HLA-identical chromosomes also carried identical microsatellites, suggesting that these loci could be applied for identification of haplotypes which have a relatively recent shared origins. Finally, when the microsatellites were studied between ethnically more distant individuals (Finnish vs. non-Finnish), who were matched for the HLA alleles, much more differences were observed. This showed that the similarity in microsatellites was population specific. The microsatellite typing can therefore be informative in fine mapping MHC-linked susceptibility genes and can help in matching bone marrow transplants in isolated populations. Linkage disequilibrium was found to be much higher in the MHC than in another region (5q31) of similar size, indicating that there may be particular mechanisms keeping the MHC haplotypes conserved. [ABSTRACT FROM AUTHOR]

Since her shipwreck in 1771, the wooden vessel Vrouw Maria has been lying on the seabed at 41 m depth on the border between the Archipelago Sea and the northern Baltic proper, off the southern coast of Finland. The wreck lies in an upward position in a right angle to the dominating bottom current, which is potentially affecting seabed topography, sediment characteristics and zoobenthic communities both upstream (NE) and downstream (SW) of the wreck. This multidisciplinary study attempts to clarify abiotic and biotic patterns and processes in the vicinity of the wreck by combining field investigations with physical simulation studies in the field and in the laboratory. Multibeam echo-sounder techniques were utilised to generate a map of the wreck area and sediment grab samples were taken to characterize the sediment type and its zoobenthic community. A medium-sized field experiment generated data on the accumulation of sediment organic matter in the presence and absence of a current and/or a barrier on the seafloor and a small-scaled laboratory study was conducted to simulate scour forming processes. The results showed that a deeper basin, scour area, with the dimensions 150×300 m, was present downstream of the wreck and there was also a smaller scour area upstream of the wreck. Similar traces on the bottom were simulated in the laboratory. The organic content (recent mud) and the proportion of finer sediment were more pronounced in areas closer to both sides of the wreck. These results were in turn imitated in a field experiment, where the accumulation of organic matter in the sediment increased significantly downstream, when a current was interrupted by a barrier. Regarding zoobenthos in the wreck area, 11 taxa and a mean total abundance of 773 individuals per m 2 were registered. The dominant species were Macoma balthica and Marenzelleria sp., which together made up >80% of the total number of individuals. Multivariate data analyses showed significant differences in community structure between upstream and downstream sides of the wreck and these differences were basically expressed as more individuals upstream of the wreck of the seven most common species. Univariate data analyses also showed significantly more species and higher total abundance in the scour area upstream of the wreck compared to the downstream scour area. The weakened communities downstream of the wreck were possibly due to accumulation of organic matter and more frequent occurrence of hypoxia. The results are useful for describing bottom areas around long-term physical barriers/artificial reefs, as background measurements ahead of possibly increased archaeological diving activities, sediment excavations or measures taken to raise the wreck to the surface, as well as for any attempts to preserve the wreck in situ. [ABSTRACT FROM AUTHOR]