Edwards C Q, Griffen L M, Dadone M M, Skolnick M H, Kushner J P
Am J Hum Genet. 1986 Jun;38(6):805-11.
We studied a family with HLA-linked hereditary hemochromatosis in which an informative recombination occurred within the HLA region. The father, an obligate heterozygote for hereditary hemochromatosis, had HLA haplotypes A2,B13 and A11,B27. The mother, also an obligate heterozygote, had HLA haplotypes A29,B44 and A2,B7. Three haplotypes were found among three homozygous affected offspring. Two affected siblings were HLA-identical with haplotypes A2,B13 and A29,B44. The proband had HLA haplotypes A2,B13 and A2,B44, the latter a recombinant haplotype inherited from her mother. Since the maternal hemochromatosis allele was linked to the A29,B44 haplotype, and since the proband has hemochromatosis, the maternal hemochromatosis allele was transmitted to the proband with the B44 antigen. This is the first known example of recombination in an individual with HLA-linked hemochromatosis in whom the hemochromatosis allele appeared to segregate with the HLA-B antigen instead of the -A antigen. The possibility of either a double reciprocal recombination event or a gene conversion event cannot be excluded. Combined with earlier observations of segregation of the hemochromatosis allele with the A locus in HLA recombinants, the findings in this pedigree map the hemochromatosis locus between the HLA-B and HLA-A loci rather than outside the HLA region.
我们研究了一个与HLA连锁的遗传性血色素沉着症家族，其中在HLA区域内发生了一次信息性重组。父亲是遗传性血色素沉着症的必然杂合子，其HLA单倍型为A2、B13和A11、B27。母亲也是必然杂合子，其HLA单倍型为A29、B44和A2、B7。在三个纯合患病后代中发现了三种单倍型。两名患病的兄弟姐妹HLA相同，单倍型为A2、B13和A29、B44。先证者的HLA单倍型为A2、B13和A2、B44，后者是从她母亲那里遗传来的重组单倍型。由于母亲的血色素沉着症等位基因与A29、B44单倍型连锁，且先证者患有血色素沉着症，所以母亲的血色素沉着症等位基因与B44抗原一起传递给了先证者。这是已知的HLA连锁血色素沉着症个体中发生重组的首个例子，其中血色素沉着症等位基因似乎与HLA - B抗原而非 - A抗原分离。不能排除双相互易位重组事件或基因转换事件的可能性。结合早期关于HLA重组体中血色素沉着症等位基因与A位点分离的观察结果，该家系中的发现将血色素沉着症基因座定位在HLA - B和HLA - A基因座之间，而非HLA区域之外。
