The association between HLA-A alleles and an Alu dimorphism near HLA-G

The AluYb8 sequences are a subfamily of short interspersed Alu retroelement s that have been amplified within the human genome during recent evolutiona ry time and are useful polymorphic markers for studies on the origin of hum an populations. We have identified a new member of the Yb8 subfamily, AluyH G, located between the HLA-H and -G genes and 88-kb telomeric of the highly polymorphic HLA-A gene within the alpha block of the major histocompatibil ity complex (MHC). The AluyHG element was characterised with a view to exam ining the association between AluyHG and HLA-A polymorphism and reconstruct ing the history of the MHC alpha block. A specific primer pair was designed for a simple PCR assay to detect the absence or presence (dimorphism) of t he AluyHG element within the DNA samples prepared from a panel of 46 homozy gous cell-lines containing complete or recombinant ancestral haplotypes (AH ) of diverse ethnic origin and 92 Caucasoid and Asian subjects on which HLA -A typing was available. The AluyHG insertion was most strongly associated with HLA-A2 and, to a lesser degree with HLA-A1, -A3, -A11, and A-19. The g ene frequency of the AluyHG insertion for 146 Caucasians and 94 Chinese-Han was 0.30 and 0.32 and there was no significant difference between the obse rved and expected frequencies. The results of the association studies and t he phylogenetic analysis of HLA-A alleles suggest that the AluyHG sequence was integrated within the progenitor of HLA-A2, but has been transferred by recombination to other human ancestral populations. In this regard, the di morphic AluyHG element is an important diagnostic marker for HLA associatio n studies and could help in elucidating the evolution and functions of the MHC alpha block and polymorphism within and between ancestral haplotypes.