33–39 Of the 418 haplotypes of the parents of the 104 families (haplotype information was derived from three parents in one family), there were 122 different haplotypes, taking into account both genes and alleles. Of these, 48 were A and 74 were B. Sixty-six haplotypes only occurred on one occasion. In total, 230 (55%) of haplotypes were A and 188 (45%) were B. The percentage of individuals who were homozygous for the A haplotype was Obeticholic Acid 32·3%, the percentage homozygous for the B haplotype was 12·1% and 55·6% of individuals had both A and B haplotypes. B haplotypes have previously

been shown to be more prevalent in non-Caucasian populations such as Australia Aborigines and Asian RO4929097 datasheet Indians,40–43 whereas in Caucasian populations approximately 55% of the population will have A haplotypes and 30% have two A haplotypes.44 It is believed that populations with higher frequencies

of B haplotypes will be those under strong pressure from infectious diseases. The addition of 27 new families to the haplotype study resulted in the definition of 19 new individual haplotypes, some of which occurred more than once. This would indicate that even in a small ethnically homogeneous population, the number of families (77 in the original report) needs to be greatly increased to cover all potential haplotype variation. It is important to note that genes normally associated with the A haplotype can also be found on the B haplotype. These genes, KIR3DL1, KIR2DS4, KIR2DL1, KIR2DL3, were present on 102, 99, 113 and 52 of the 188 B haplotypes, respectively. Ninety-six B haplotypes had both 3-mercaptopyruvate sulfurtransferase KIR3DL1 and KIR2DS4. The only activating gene, bar KIR2DL4,

on the A haplotype is KIR2DS4. There are two versions of KIR2DS4, one with the full sequence and one with a short deletion. The deleted version has a 22-base-pair deletion in exon 5, which causes a frame shift leading to a stop codon in exon 745 and it is believed that this version is not expressed at the cell surface. The deleted version (KIR2DS4 alleles *003,004,006,007) is quite common, at 80% in the Northern Ireland population, nearly 60% of the population having only the deleted KIR2DS4. However, there is a trend for decreased frequency of the deleted version in those populations that are homozygous for the A haplotypes.46 Interestingly we found that 30 (62·5%) of the different A haplotypes and 155 (67·4%) of total A haplotypes contained both a deleted version of KIR2DS4 and a deleted version of KIR2DL4, (2DL4-9A). Consequently, in those individuals who have the genotype AA, 43·1% did not have an activating KIR, leading to 13·9% in the overall population not having an activating receptor.