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DNA Research 2000 7(3):195-206; doi:10.1093/dnares/7.3.195
© 2000 by Kazusa DNA Research Institute
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Sequence-based Structural Features between Kvlqt1 and Tapa1 on Mouse Chromosome 7F4/F5 Corresponding to the Beckwith-Wiedemann Syndrome Region on Human 11p15.5 : long-stretches of Unusually Well Conserved Intronic Sequences of Kvlqt1 between Mouse and Human

Hitomi Yatsuki1, Hidemi Watanabe2, Masahira Hattori2, Keiichiro Joh1, Hidenobu Soejima1, Hiroshi Komoda1, Zhenghan Xin1, Xike Zhu1, Ken Higashimoto1, Masayo Nishimura1, Shinobu Kuratomi1, Hiroyuki Sasaki3, Yoshiyuki Sakaki2,4 and Tsunehiro Mukai1,*

1Department of Biochemistry, Saga Medical School 5-1-1 Nabeshima, Saga, Saga 849-8501, Japan
2RIKEN Genomic Science Center (GSC), Human Genome Research Group, c/o Kitasato University 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan
3Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics and Department of Genetics, Graduate University for Advanced Studies 1-111 Yata, Mishima, Shizuoka 411-8540, Japan
4Human Genome Center, Institute of Medical Science, University of Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

* To whom correspondence should be addressed. Tel. +81-952-34-2260, Fax. +81-952-34-2067, E-mail: mukait{at}post.sagamed.ac.jp

Mouse chromosome 7F4/F5 is a syntenic locus of human 11p15.5 in which many imprinted genes are clustered. Transmission of aberrant human 11p15.5 or duplicated 11p causes Beckwith-Wiedemann syndrome (BWS) depending on which parent the chromosome is derived from. To analyze a syntenic mouse locus corresponding to human 11p15.5, mouse BAC contigs were constructed between Nap2 and Tapa1, in which 390 kb was sequenced between Kvlqt1 and Tapa1. An unexpected finding was that of highlyconserved intronic sequences of Kvlqt1 between mouse and human, and their homologies came up to at least 160 kb because the length of this gene extended to 350 kb, suggesting the possibilityof some functional constraint due to transcriptional and/or post-transcriptional regulation of this region. Manyexpressed sequence tags (ESTs) were mapped on this locus. Three genes, Lit1 (Kvlqt1-AS), Mtr1 and Tssc4, were identified and characterized. Lit1 is an antisense-transcript of Kvlqt1 and paternally expressed and maternally methylated throughout the developmental stage. The position where Lit1 exists corresponded to a highly conserved region between mouse and human. This transcript extends at least 60 kb from downstream to upstream of exon 10 in Kvlqt1. Tssc4 and Mtr1 carried putative open reading frames but neither was imprinted. Further characterization of this locus based on the sequence comparison between mouse and human will contribute valuable information towards resolving the mechanism of the occurrence of BWS and the associated childhood tumor.

Key words: genomic imprinting; mouse chromosome 7F4/F5; Lit1 (Kvlqt1-AS); Mtr1; Tssc4


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