D Middleton

..This review updates the on-going investigations into KIR genes and their alleles with the main emphasis on what has taken place in this laboratory over the last 3 years...

..An increase in the frequency of the activating KIR2DS1 gene was detected in the PsA patients, compared with psoriasis patients negative for PsA and an unaffected American Caucasian control group...

..The last two decades have seen a massive growth in the application of DNA technology in Histocompatibility and Immunogenetics. This review summarises the history and application of DNA methods in this area...

..To introduce this work, we provide an introduction to KIR receptors and an outline of previous applications of KIR receptor typing prior to the Workshop...

..A trend was observed towards decreased frequencies of KIR2DS4 deleted variant occurrence in populations having KIR2DS4 as the only activating KIR gene...

..In addition, knowing which alleles do/do not occur in this population will aid in the distinction of ambiguities which result from the use of many of the typing kits available...

..Data for HLA alleles has been added but this will be extended to include frequency data of polymorphisms in other immunogenetic regions, e.g. cytokines, KIR receptors, MIC...

..The roles that NK cells and their receptors have with various facets of transplantation, disease, pregnancy and control of virus infection in humans are described...

..Furthermore, no differences were found when the patients were sub-divided according to gender or shared epitope and when the presence of the human leucocyte antigen ligand was taken into account...

..Discussion took place on nomenclature issues of the KIR genes and their alleles, and a website has been developed to collect frequencies of KIR genes and alleles in various diverse populations...

..1%, 9.7% and 12.6% for KIR2DL4, KIR3DL2 and KIR3DL1 genes, respectively, but 62.6% and 53% for KIR2DL3 and KIR2DS4 genes, respectively, despite the fact that no one allele dominated the frequency in any of these genes...

..The KIR gene 2DS5 was significantly decreased in patients versus controls, but this was no longer significant after correction for the number of comparisons made...

..Finally, in the group of colorectal carcinomas, there was an overall significant difference in the frequencies of C group heterozygosity and homozygosity with HLA alterations on the tumour...

..Thus, no association was identified between presence or absence of any of the 14 KIR genes studied and BD. In addition, we did not find any associations of KIR with various manifestations of the disease nor with gender or age of onset...

..These three novel alleles may have originated from other HLA alleles by gene conversion. However, it is also possible that HLA-A*2471 has evolved from one of the alleles of the HLA-A*2402 group through a point mutation...

..Its unique gene structure gives a possible insight into the evolutionary pathway that created HLA class I genes...

..Results also indicated an inherited KIR2DL1/2DS1 splice variant present in a haplotype with several core loci absent, in two families...

..HLA-B allele frequencies and HLA-A/B two locus haplotype frequencies were compiled for each population...

..It would appear by their presence in all populations studied, either rural or indigenous, that certain alleles are very important in pathogen peptide presentation...

..A high level of KIR3DL2 allelic polymorphism has been identified...

..This information complements published reports by our laboratory for allele-level typing of other KIR members, totaling 12 of the 17 known genes. These methods are allowing us to characterize KIR haplotypes in our population...

..Parallels with a recent study in the rhesus monkey highlighting access to the same open reading frame as the deletion variant, also predicting a soluble KIR molecule, are drawn...

..There is no evidence of a protective effect for the S-allele of the HO-1 gene promoter polymorphism on graft or recipient survival in clinical renal transplantation...

..In addition we confirm the existence of HLA-B*4415, an allele closely related to HLA-B*4501 differing only at the Bw4/Bw6 epitope...

..We found no association in frequencies of the alleles of these genes in AS. In addition, no differences were found when the patients and controls were differentiated by gender...

..Our data predicts that the HLA-B*1501 null allele would express a small truncated protein containing the signal sequence fused to an ORF within intron 1 and terminating (out of frame) just within exon 2...

..To date, 286 HLA-B alleles have been identified and characterised. We describe a new HLA-B*07 allele present in a Cuban Caucasoid individual, which has been officially named HLA-B*0720...

..Use of the PCR-SSOP system has confirmed the presence of multiple copies of KIR3DL1/S1 alleles in a number of individuals...

..These findings would suggest that polymorphism of cytokine genes may not play as crucial a role in healthy ageing as previously believed...

..However, no age-related allele or genotype frequencies were observed for either polymorphic nucleotide...

..The segregation analysis concluded that at least 3 distinct gene loci encode 2DL1-4 and at least 4 gene loci encode the non-inhibitory KIR2DS1-2DS5. In the case of 3DL1-2 and 3DS1, our data suggests 3 gene loci, one for each subfamily...

..When the method was applied to the typing of 66 consecutive cadaveric donors there were three donors whose type differed from the serological type...

..In addition, cell line DNA and Centre d'Etude du Humaine (CEPH) families, both from the 13th International Histocompatibility Workshop have been investigated, establishing control data for this gene...

..Haplotype segregation, with respect to KIR2DS4 alleles, has been examined by using the local family data. Within all sample groups investigated, four KIR2DS4 alleles were identified, two of which are novel to this investigation...

..Five populations were investigated, Northern Ireland, South African Zulu, Omani, Singapore Chinese and Mexican Mestizos...

..allelefrequencies.net). In total, 5134 individuals were analysed and the populations grouped, with some exceptions, according to a geographical gradient...

..164...

..In view of the lack of studies to date, investigating the role of the KIR gene system in healthy ageing, further analysis of KIR diversity is required to fully elucidate it's role in respect to age-related disease and longevity...

..This study observed no differences in the frequency of cytokine promoter polymorphisms associated with variant levels of expression in patients with CF and a non-CF population of Northern Ireland...

..This study was conducted to determine if a difference exists in human leukocyte antigen (HLA) allele distribution between patients with AAA and population controls, and between patients with small and large AAA...

..It is our assumption that an unequal crossover event has occurred between differing KIR haplotypes resulting in the duplication of the 2DL4, 3DS1/3DL1 genes on the newly formed haplotype(s)...

..Additionally, the KIR2DL4 allele status of cell line DNA and CEPH families, from the 13th International Histocompatibility Workshop and local families, have also been investigated...

..HLA-Cw allele frequencies occurring within the Northern Ireland population have been compiled, along with estimations of HLA-B/Cw haplotype frequencies...

..This technique displays enormous potential as an alternative to DNA sequence determination and has the potential to become an automated technique that can be implemented in the routine setting...

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..Evidence for selection was seen on haplotypes HLA-A*010101-B*0801-DRB1*030101 and HLA-A*290201-B*440301-DRB1*070101 based on their patterns of linkage disequilibrium...

..8% vs 80.8%; P=0.98) or family-based (49.7% transmissions; P=0.94) studies. Our results do not support earlier reports of an association between allele 1 in the 3'UTR of the IL12B gene and type 1 diabetes...

..It appears that HLA-B*3569 arose from the analogous HLA-B*3510 through a point mutation. However, HLA-B*4450 may have arisen from HLA-B*440301 and -B*4425 by gene conversion...

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..The ongoing refinement of KIR haplotype distribution in our control population will help in disease association studies involving the KIR genes...

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..Thus, variation of KIR expression on cell surfaces more likely involves post-transcriptional mechanisms...

..These findings lead one to postulate that the mt4216C variant, in linkage with the mtDNA TJ cluster, may influence mitochondrial dysfunction, resulting in an increased risk of PD...

..These results would suggest that polymorphism of the alpha-synuclein gene may not play as significant a role in the pathogenesis of idiopathic PD as previously hypothesised...

..We report the first assessment of the role of this HO-1 gene promoter polymorphism in chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IgAN)...

..A similar explanation may also apply to the in vitro model of T cell ageing if the vast majority of the cells are replicating rather than entering senescence...

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..The putative KIR3DP1*004 product, like those of the related genes LAIR-2 and LILRA3/ILT6/LIR4, is predicted to be secreted to the extracellular medium rather than anchored to the cell membrane...

..Despite this African genetic input, haplotype and allele frequencies were predominantly from European origin, mostly common to mainland Portugal...

..Our results provide useful information for the further studies of the Cuban population evolution and disease association in terms of HLA class I genes...

..No effect of KIR ligand matching on graft survival was observed in cadaver kidney transplants. Our results indicate that KIR ligand matching cannot be recommended as a strategy for improving renal allograft survival...

..Dendrograms and principal coordinates analysis show that Guineans are more similar to North Africans than other HLA-studied sub-Saharans, probably from ancient and recent genetic contacts with other peoples, namely East Africans...

..In contrast to the inhibitory KIR3DL1 allotypes, KIR3DS1 did not recognize HLA-Bw4 on EBV-transformed cell lines...

..These results show the involvement of KIR-MHC class I interactions in the calibration of NK cell effector capacities, suggesting its role in the subsequent "missing self" recognition...

..Further improvements in typing may be required if population and clinical studies are to produce accurate results...

..Whether or not natural selection has acted to enrich group-B KIR haplotypes in these migratory descendants is an issue that requires objective testing...

..The poor outcome associated with very young donors should discourage pediatric units from transplanting kidneys from such young donors. The reasons for late losses in older recipients need investigation...

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..New methods or variations of existing methods are continually being developed. However the cost of equipment makes it difficult for a laboratory to decide on which methods to use...