Variation of GT-repeat numbers associated with haplotype structure of human DNA ligase I locus
| Autor: | Michikawa, Yuichi, Suga, Tomo, Kouda, Masakazu, Ootsuka, Yoshimi, Suzuki, Hideyuki, Saegusa, Kumiko, Furuno, Aki, Ishikawa, Ken-ichi, Ishikawa, Atsuko, Kawai, Seiko, Tsuji, Atsushi, Sugyou, Aya, Noda, Shuhei, Iwakawa, Mayumi, Imai, Takashi |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Popis: | During the course of studying the genetic determinants of normal tissue injury after radiotherapy of cancer patients, we have detected positive correlation of some intronic SNPs on human DNA ligase I locus of chromosome 19 to the severity of the injury. The human DNA ligase I gene has three consecutive GT-repeat sequences franked by the same polypurine-rich sequence at a place very close to the exon-intron boundary of an alternatively spliced intron. In this study, we have analyzed stability of the GT-repeat sequences among individuals and haplotype structure surrounding this locus. The genomic region containing the above sequences were amplified from the blood DNA of 9 cancer patients by PCR and cloned into TA-cloning vector. Plasmid DNAs from 6 independent colonies of each transformant were purified and sequenced, respectively. We observed variations of the all three GT-repeats among cancer patients and also among the clones from each individual. Haplotype structure of the 4 SNPs that surround the GT-repeat sequences was estimated using the EM algorism. The nine cancer individuals were divided into 3 groups according to the above estimated haplotypes. By comparing the haplotype structure and the GT-repeat sequences, we found that the GT-repeat sequence that located closest to the exon-intron boundary seemed to have solid threshold range in variation for each haplotype. Functional relevance of the human DNA ligase I gene haplotype with different threshold range in length variation of GT-repeat sequence, in a sense related to the individual's radiation sensitivity, will be elucidated in further study. ASHG Meeting 2004 |
| Databáze: | OpenAIRE |
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