Westaway D, Williamson R
Nucleic Acids Res. 1981 Apr 24;9(8):1777-88. doi: 10.1093/nar/9.8.1777.
A 7.5 kb Hsu I restriction fragment of genomic DNA containing a beta-globin gene has been isolated from a patient doubly heterozygous for beta + thalassaemia and a delta beta (Lepore globin fusion gene. This fragment must be derived from the chromosome carrying the beta +-thalassaemia determinant. The gross structure of the cloned gene plus flanking sequences is indistinguishable from that of a normal beta-globin gene. Within in 1606 base-pair transcribed region of the gene there is only one nucleotide difference from the normal beta-globin gene sequence. This is a G leads to A replacement 21 nucleotides upstream from the 3' terminus of the small intron. This nucleotide lies within a 10 base-pair sequence repeated in an inverted configuration near the 5' terminus of the small intron. The nucleotide replacement may result in a precursor mRNA less amenable to RNA splicing than its normal counterpart.
已从一名β⁺地中海贫血和δβ（Lepore珠蛋白融合基因）双重杂合子患者中分离出一个含有β-珠蛋白基因的7.5 kb Hsu I基因组DNA限制性片段。该片段必定来自携带β⁺地中海贫血决定簇的染色体。克隆基因及其侧翼序列的总体结构与正常β-珠蛋白基因无异。在该基因1606个碱基对的转录区域内，与正常β-珠蛋白基因序列仅有一个核苷酸差异。这是一个位于小内含子3'末端上游21个核苷酸处的G突变为A。该核苷酸位于小内含子5'末端附近以反向构型重复的一个10碱基对序列内。这种核苷酸替换可能导致前体mRNA比其正常对应物更不易于进行RNA剪接。
