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

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 du plicated 11p causes Beckwith-Wiedemann syndrome (BWS) depending on which pa rent the chromosome is derived from. To analyze a syntenic mouse locus corr esponding to human 11p15.5, mouse BAC contigs were constructed between Nap2 and Tapa1, in which 390 kb was sequenced between Kvlqt1 and Tapa1. An unex pected finding was that of highly conserved intronic sequences of Kvlqt1 be tween mouse and human, and their homologies came up to at least 160 kb beca use the length of this gene extended to 350 kb, suggesting the possibility of some functional constraint due to transcriptional and/or post-transcript ional regulation of this region. Many expressed sequence tags (ESTs) were m apped on this locus. Three genes, Lit1 (Kvlqt1-AS), Mtr1 and Tssc4, were id entified and characterized. Lit1 is an antisense-transcript of Kvlqt1 and p aternally expressed and maternally methylated throughout the developmental stage. The position where Lit1 exists corresponded to a highly conserved re gion between mouse and human. This transcript extends at least 60 kb from d ownstream 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 c ontribute valuable information towards resolving the mechanism of the occur rence of BWS and the associated childhood turner.