Contu L, Carcassi C, Dausset J
Department of Medical Genetics, University of Cagliari, Italy.
Immunogenetics. 1989;30(1):13-7. doi: 10.1007/BF02421464.
The C4 and 21-OH loci of the class III HLA have been studied by specific DNA probes and the restriction enzyme Taq 1 in 24 unrelated Sardinian individuals selected from completely HLA-typed families. All 24 individuals had the HLA extended haplotype A30,Cw5,B18, BfF1,DR3,DRw52,DQw2, named "Sardinian" in the present paper because of its frequency of 15% in the Sardinian population. Eighteen of these were homozygous for the entire haplotype, and six were heterozygous at the A locus and blank (or homozygous) at all the other loci. In all completely homozygous cells and in four heterozygous cells at the A locus, the restriction fragments of the 21-OHA (3.2 kb) and C4B (5.8 kb or 5.4 kb) genes were absent, and the fragments of the C4A (7.0 kb) and 21-OHB (3.7 kb) genes were present. It is suggested that the "Sardinian" haplotype is an ancestral haplotype without duplication of the C4 and 21-OH genes, practically always identical in its structure, also in unrelated individuals. The diversity of this haplotype in the class III region (about 30 kb less) may be at least partially responsible for its misalignment with most haplotypes, which have duplicated C4 and 21-OH genes, and therefore also for its decreased probability to recombine. This can help explain its high stability and frequency in the Sardinian population. The same conclusion can be suggested for the Caucasian extended haplotype A1,B8,DR3 that always seems to lack the C4A and 21-OHA genes.
运用特异性DNA探针和限制性内切酶Taq 1，对从完全进行了HLA分型的家族中选取的24名撒丁岛无关个体的Ⅲ类HLA的C4和21-OH基因座进行了研究。所有这24名个体都具有HLA扩展单倍型A30、Cw5、B18、BfF1、DR3、DRw52、DQw2，在本文中命名为“撒丁岛型”，因为其在撒丁岛人群中的频率为15%。其中18人对整个单倍型呈纯合状态，6人在A基因座为杂合，而在所有其他基因座为空白（或纯合）。在所有完全纯合的细胞以及A基因座的4个杂合细胞中，21-OHA（3.2 kb）和C4B（5.8 kb或5.4 kb）基因的限制性片段缺失，而C4A（7.0 kb）和21-OHB（3.7 kb）基因的片段存在。提示“撒丁岛型”单倍型是一种没有C4和21-OH基因重复的祖先单倍型，实际上其结构始终相同，在无关个体中也是如此。该单倍型在Ⅲ类区域（约少30 kb）的多样性可能至少部分地导致了其与大多数具有C4和21-OH基因重复的单倍型的错配，因此也导致了其重组概率降低。这有助于解释其在撒丁岛人群中的高稳定性和高频率。对于似乎始终缺乏C4A和21-OHA基因的白种人扩展单倍型A1、B8、DR3，也可得出相同结论。
