An insertion mutation of the bovine F11 gene is responsible for factor XI deficiency in Japanese black cattle
An insertion mutation of the bovine F11 gene is responsible for factor XI deficiency in Japanese black cattle
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DOI：
10.1007/s00335-004-2462-5
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发表时间：
2005-05-01
期刊：
影响因子：
2.5
通讯作者：
Kunieda, T
中科院分区：
文献类型：
--
作者：
Kunieda, M;Tsuji, T;Kunieda, T
日本黑牛因子XI缺乏症是一种常染色体隐性遗传的遗传性轻度出血性疾病。为了表征牛病变因子XI缺乏的分子特征，我们分离了牛F11基因的整个编码区，包括15个外显子和14个内含子，并确定了其核苷酸序列。比较患病动物和未患病动物的F11基因的核苷酸序列发现，在患病动物的第9外显子上插入了15个核苷酸。该插入导致因子XI蛋白第4苹果结构域高度保守的氨基酸序列中1个氨基酸被6个氨基酸取代。对109头日本黑牛的F11基因分型结果表明，该基因的插入与牛的XI因子活性密切相关。因此，我们得出结论，在F11基因中插入15个核苷酸是导致日本黑牛缺乏因子XI的致病突变。通过检测插入的f11基因分型将是一种有效的基于dna的诊断系统，可以预防疾病的发生。
Factor XI deficiency in Japanese black cattle is an hereditary mild bleeding disorder with an autosomal recessive mode of inheritance. To characterize the molecular lesion causing factor XI deficiency in cattle, we isolated an entire coding region of the bovine F11 gene, which comprises 15 exons and 14 introns, and determined its nucleotide sequences. Comparison of the nucleotide sequences of the F11 gene between affected and unaffected animals revealed an insertion of 15 nucleotides in exon 9 of the affected animals. The insertion results in a substitution of one amino acid with six amino acids in a highly conserved amino acid sequence in the fourth apple domain of factor XI protein. Genotyping of the F11 gene in 109 Japanese black cattle revealed that the insertion clearly corresponded to the factor XI activities of the animals. We therefore concluded that the insertion of 15 nucleotides in the F11 gene is the causative mutation for factor XI deficiency in Japanese black cattle. Genotyping of the F11gene by detecting the insertion will be an effective DNA-based diagnostic system to prevent incidence of the disease.