Sequence conservation and variability of imprinting in the Beckwith-Wiedemann syndrome gene cluster in human and mouse

In human and mouse most imprinted genes are arranged in chromosomal cluster s. This linked organization suggests coordinated mechanisms expression. We have organization controlling in sequenced 250 kb in the centre of the mous e imprinting cluster on distal chromosome 7 and compared it with the orthol ogous Beckwith-Wiedemann gene cluster on human chromosome 11p15.5, This fir st comparative imprinting cluster analysis revealed a high structural and f unctional conservation of the six orthologous genes identified, However, se veral striking differences were also discovered, First, compared with the m ouse the human sequence is similar to 40% longer, mostly due to insertions of two large repetitive clusters, One of these clusters encompasses an addi tional gene coding for a homologue of the ribosomal protein L26. Second, pr onounced blocks of unique direct repeats characteristic of imprinted genes were only found in the human sequence. Third, two of the orthologous gene p airs Tssc4/TSSC4 and Ltrpc5/LTRPC5 showed apparent differences in imprintin g between human and mouse, whereas others like Tssc6/TSSC6 were not imprint ed in either organism, Together these results suggest a significant functio nal and structural variability in the centre of the imprinting cluster. Som e genes escape imprinting in both organisms whereas others exhibit tissue- and species-specific imprinting. Hence the control of imprinting in the clu ster appears to be a highly dynamic process under fast evolutionary adaptat ion. Intriguingly, whereas imprinted genes within the cluster contain CpG i slands the non-imprinted Ltrpc5 and Tssc6/TSSC6 do not, This and additional comparisons with other imprinted and non-imprinted regions suggest that Cp G islands are key features of imprinted domains.