MOLECULAR MAPPING OF A RECOMBINATION HOTSPOT LOCATED IN THE 2ND INTRON OF THE HUMAN TAP2 LOCUS

Recombination across the HLA class II region is not randomly distribut ed, as indicated by both strong linkage disequilibrium within the 100 kb encompassing the DRB1-DQA1-DQB1 loci and complete equilibrium betwe en TAP1 and TAP2, the closest variant sites of which are <15 kb. In an attempt to explain these observations, 39 novel polymorphic markers i n a region encompassing the TAP, LMP, and DOB genes were used to delin eate the site of crossover in 11 class II recombinant chromosomes. SSC P demonstrated that two recombination events occurred within an 850-bp interval in the second intron of TAP2, which separates the variant si tes of TAP1 and TAP2. These data indicate the presence of a recombinat ion hotspot, the first to be identified from the analysis of familial transmission in the human major histocompatibility complex. The region of crossover was cloned and sequenced from one of the recombinants, f urther defining the crossover site to a 138-bp segment nested within t he 850-bp region. This represents the most precisely defined region of recombination in the human genome.