Zuliani G, Hobbs H H
Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas 75235.
Am J Hum Genet. 1990 May;46(5):963-9.
We describe a new class of DNA length polymorphism that is due to a variation in the number of tandem repeats associated with Alu sequences (Alu sequence-related polymorphisms). The polymerase chain reaction was used to selectively amplify a (TTA)n repeat identified in the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase gene from genomic DNA of 41 human subjects, and the size of the amplified products was determined by gel electrophoresis. Seven alleles were found that differed in size by integrals of three nucleotides. The allele frequencies ranged from 1.5% to 52%, and the overall heterozygosity index was 62%. The polymorphic TTA repeat was located adjacent to a repetitive sequence of the Alu family. A homology search of human genomic DNA sequences for the trinucleotide TTA (at least five members in length) revealed tandem repeats in six other genes. Three of the six (TTA)n repeats were located adjacent to Alu sequences, and two of the three (in the genes for beta-tubulin and interleukin-1 alpha) were found to be polymorphic in length. Tandemly repetitive sequences found in association with Alu sequences may be frequent sites of length polymorphism that can be used as genetic markers for gene mapping or linkage analysis.
我们描述了一类新的DNA长度多态性，它是由于与Alu序列相关的串联重复序列数量的变化所致（Alu序列相关多态性）。利用聚合酶链反应从41名人类受试者的基因组DNA中选择性扩增在3-羟基-3-甲基戊二酰辅酶A（HMG CoA）还原酶基因中鉴定出的（TTA）n重复序列，并通过凝胶电泳确定扩增产物的大小。发现了7个等位基因，其大小相差三个核苷酸的整数倍。等位基因频率范围为1.5%至52%，总体杂合度指数为62%。多态性TTA重复序列位于Alu家族的一个重复序列附近。对人类基因组DNA序列进行三核苷酸TTA（长度至少为五个成员）的同源性搜索，在其他六个基因中发现了串联重复序列。六个（TTA）n重复序列中的三个位于Alu序列附近，其中三个中的两个（在β-微管蛋白和白细胞介素-1α基因中）被发现长度具有多态性。与Alu序列相关的串联重复序列可能是长度多态性的常见位点，可作为基因定位或连锁分析的遗传标记。
