BETA-THALASSEMIA IN CHINESE - USE OF INVIVO RNA ANALYSIS AND OLIGONUCLEOTIDE HYBRIDIZATION IN SYSTEMATIC CHARACTERIZATION OF MOLECULAR DEFECTS
BETA-THALASSEMIA IN CHINESE - USE OF INVIVO RNA ANALYSIS AND OLIGONUCLEOTIDE HYBRIDIZATION IN SYSTEMATIC CHARACTERIZATION OF MOLECULAR DEFECTS
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DOI：
10.1073/pnas.81.9.2821
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
KAZAZIAN, HH
中科院分区：
文献类型：
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作者：
CHENG, TC;ORKIN, SH;KAZAZIAN, HH
为了进行β-的系统分析，中国人中的地中海贫血基因，β-地中海贫血基因中的DNA单倍型，37个中国人β-珠蛋白基因区地中海贫血染色体测定。仅发现4种单倍型，单倍型1、2和3纯合子患者红系RNA的印迹杂交分析显示不同的模式，表明不同的突变与每种单倍型相关。与单倍型1相关的突变是C →。在IVS-2，位置654处的T取代。该突变产生新的供体剪接位点并导致β-插入73个核苷酸的珠蛋白RNA。与单倍型2相关的突变是在密码子71和72之间插入A的核苷酸，这导致β-D的移码和过早终止。珠蛋白合成单倍型分析表明，这2个突变可能占β-CD的高达85%。地中海贫血的基因。单倍型3基因含有先前报道的转录TATA盒突变。寡核苷酸杂交证明与单倍型4相关的突变是在β-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-HLA-地中海贫血基因在亚洲印度人。由于中国人的单倍型4在IVS-1第5位突变两侧的多态性位点与印度人的单倍型不同，该突变可能独立地出现在这些人群中。
To perform a systematic analysis of .beta.-thalassemia genes among Chinese, the DNA haplotype in the .beta.-globin gene region of 37 Chinese .beta.-thalassemia chromosomes was determined. Only 4 haplotypes were found. Blot hybridization analysis of erythroid RNA from patients homozygous for haplotypes 1, 2 and 3 demonstrated different patterns, suggesting that a different mutation was associated with each haplotype. The mutation associated with haplotype 1 was a C .fwdarw. T substitution at IVS-2, position 654. This mutation produces a new donor splice site and leads to formation of a .beta.-globin RNA with an insertion of 73 nucleotides. The mutation associated with haplotype 2 was a nucleotide insertion of A between codons 71 and 72, which results in a frameshift and premature termination of .beta.-globin synthesis. Haplotype analysis suggests that these 2 mutations may account for up to 85% of .beta.-thalassemia genes in this ethnic group. The haplotype 3 gene contained a transcriptional TATA box mutation that was previously reported. Oligonucleotide hybridization demonstrated that the mutation associated with haplotype 4 was the same IVS-1 position 5 substitution commonly observed among .beta.-thalassemia genes in Asian Indians. Since haplotype 4 of Chinese differs at polymorphic sites on either side of the IVS-1 position 5 mutation from the haplotype associated with this mutation in Indians, the mutation presumably arose independently in these populations.