RECOMBINATION RATES ACROSS THE HLA COMPLEX - USE OF MICROSATELLITES AS A RAPID SCREEN FOR RECOMBINANT CHROMOSOMES
RECOMBINATION RATES ACROSS THE HLA COMPLEX - USE OF MICROSATELLITES AS A RAPID SCREEN FOR RECOMBINANT CHROMOSOMES
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DOI：
10.1093/hmg/4.3.423
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发表时间：
1995-03-01
影响因子：
3.5
通讯作者：
CARRINGTON, M
中科院分区：
文献类型：
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作者：
MARTIN, M;MANN, D;CARRINGTON, M
减数分裂重组似乎不是随机发生在染色体之间，而是似乎仅限于特定区域。这种现象的一个突出例子是HLA II类区域。在包含DRB 1-DQA 1-DQB 1基因座的100 kb内没有报道重组，而TAP 1与TAP 2等位基因的随机关联表明在分隔这两个基因座的最近变异位点的15 kb内存在重组热点。基因座之间的重复率可以为单倍型的功能特性提供线索。缺乏重组可能表明有必要保持某些基因的等位基因的相位，或者，高重组率可能表明选择压力，以多样化的单倍型的人口。为了解决这个问题，使用59个人类多态性研究中心（CEPH）家系确定了HLA复合体的重组率。确定了4个微卫星标记的等位基因频率，这些标记定位在从复合体的端粒到着丝粒末端的位点上，并将其用作鉴定重组染色体的快速手段。分型这些以及其他多态性位点内的HLA I类，II和III类区域允许分配的重组发生的片段。II类区域（此处定义为DRB 1至DPB 1）和III类区域（此处定义为HLA-B至DRB 1）内的重组率分别为0.74%和0.94%，这两者均在预期范围内，给出了每次减数分裂每兆碱基DNA 1%重组率的标准。然而，在从HLA-A延伸到HLA-B基因座（1.4 Mb）的I类区域内测定的重组率为0.31%，显着低于预期。
Meiotic recombination does not appear to occur randomly across chromosomes, but rather seems to be restricted to specific regions. A striking example of this phenomenon is illustrated by the HLA class II region. No recombination within the 100 kb encompassing the DRB1-DQA1-DQB1 loci has been reported, whereas the random association of TAP1 with TAP2 alleles suggests the presence of a hotspot for recombination within the 15 kb separating the closest variant sites of these two loci. Recombination rates between loci may provide clues to the functional properties of haplotypes. Absence of recombination may suggest the necessity to keep alleles of certain genes in phase and, alternatively, high recombination rates may suggest selective pressure to diversify haplotypes within the population. To address this issue, recombination rates across the HLA complex were determined using the 59 Centre d'Etude Polymorphisme Humain (CEPH) pedigrees. The allele frequencies of four microsatellite markers which map at sites ranging from the telomeric to centromeric ends of the complex were determined and the markers were used as a rapid means for identification of recombinant chromosomes. Typing these as well as other polymorphic loci within the HLA class I, II and III regions allowed assignment of the segments where recombination occurred. Recombination rates within the class II region (defined here as DRB1 to DPB1) and class III region (defined here as HLA-B to DRB1) regions were 0.74% and 0.94%, respectively, both of which are within an expected range given the standard of 1% recombination rate per megabase of DNA per meiosis. The recombination rate of 0.31% determined within the class I region extending from the HLA-A to HLA-B loci (1.4 Mb), however, was significantly lower than that expected.