Length polymorphisms in human proline-rich protein genes generated by intragenic unequal crossing over.
Length polymorphisms in human proline-rich protein genes generated by intragenic unequal crossing over.
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基因内不等交换产生的人类富含脯氨酸的蛋白质基因的长度多态性。
DOI：
10.1093/genetics/120.1.267
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发表时间：
1988
期刊：
影响因子：
3.3
通讯作者：
Smithies,O
中科院分区：
文献类型：
--
作者：
Lyons,KM;Stein,JH;Smithies,O
对44个无关个体基因组DNA的Southern杂交分析表明，人类富含脯氨酸蛋白(PRP)多基因家族的BstNI型基因座(PRB1、PRB2、PRB3和PRB4)存在广泛的插入/缺失多态。克隆了10个长度变异体，包括4个pRb基因座上的等位基因，每个变异体的长度差异区域都定位在重复的第三外显子上。对其中7个等位基因进行了长度变异区域的DNA测序。结果表明：(1)PRB基因座可分为PRB1+PRB2和PRB3+PRB4两种亚型；(2)长度差异是由于第三外显子串联重复数不同所致。由于PRB1和PRB2基因座之间的同源但不相等的交换，不同数目的PRP基因座也被鉴定为变异染色体。总体数据与通过同源但不相等的基因内交换产生的观察到的长度变异是一致的。结果还表明，这些交叉事件对相互作用的DNA链之间的同源性很敏感。在PRB基因座上，至少有20次等位基因长度变异独立出现，但在PRH基因座上只检测到一个。对PRB和PRH基因重复区域详细结构的比较表明，PRB基因中的重复序列在序列和长度上都非常相似。PRH基因包含较少的重复，它们的个体长度有很大的差异。这些差异表明，与PRH基因相比，PRB基因中较多的长度变异与其更容易进行同源但不相等的配对有关。
Southern blot hybridization analysis of genomic DNAs from 44 unrelated individuals revealed extensive insertion/deletion polymorphisms within the BstNI-type loci (PRB1, PRB2, PRB3 and PRB4) of the human proline-rich protein (PRP) multigene family. Ten length variants were cloned, including alleles at each of the four PRB loci, and in every case the region of length difference was localized to the tandemly repetitious third exon. DNA sequences covering the region of length variation were determined for seven of the alleles. The data indicate (1) that the PRB loci can be divided into two subtypes, PRB1 plus PRB2, and PRB3 plus PRB4, and (2) that the length differences result from different numbers of tandem repeats in the third exons. Variant chromosomes were also identified with different numbers of PRP loci resulting from homologous but unequal exchange between the PRB1 and PRB2 loci. The overall data are compatible with the observed length variants having been generated via homologous but unequal intragenic exchange. The results also indicate that these crossover events are sensitive to the amount of homology shared between the interacting DNA strands. Allelic length variants have arisen independently at least 20 times at the PRB loci, but only one has been detected at a PRH locus. Comparison of the detailed structures of the repetitious regions in PRB and PRH loci shows that the repeats in PRB genes are very similar to each other in sequence and in length. The PRH genes contain fewer repeats, which differ considerably in their individual lengths. These differences suggest that the larger number of length variants in PRB genes is related to their greater ease of homologous but unequal pairing compared to PRH genes.