International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)


A8. Comparative Mapping and Sequencing of a 140 kb Region at the Telomere of Human Chromosome 22 Containing 9 Genes

Luc J Smink David M Lloyd, Owen T McCann, Richard Bruskiewich, Ewan Birney, Adrienne R Hunt and Ian Dunham.
Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.

The region orthologous to a 140 kb segment at the telomere of human chromosome 22 (22q13.3) was mapped and sequenced in mouse. All 8 annotated human genes were found in the mouse sequence. The annotated sequences for both clones were then used in extensive comparative analysis. The sequences were aligned by dot plots (Dotter) and percentage identity plots (PIP). This revealed a putative ninth gene. Reanalysis of the human sequence identified a number of new overlapping and splicing EST sequences mapping to the homologous region in human hence confirming the existence of the putative gene.

Additional analyses performed were comparison of exon and intron sizes, protein features, GC plots, splice sites using Sequence Logos (Schneider and Stephens, 1990) and repeat content. The two sequences showed conservation of several features including gene order and content, exon size and to a lesser extent intron size, protein features, GC profile and splice sites. The comparison of the repeat content showed a greater density of LTR/MaLR repeats in mouse, which is most likely contributable to the still expanding MaLR repeats in mouse. The coverage of repeats in this region is greater in human, due to the larger size of human Alu repeats as compared to the mouse B1/B2 repeats (Smit, 1996).

The dot plot and PIP did not reveal any significant conservation upstream of transcription start sites of genes in this region, although the GC profiles seemed to suggest conservation of CpG islands. Using the same prediction algorithm for CpG islands fewer were found in mouse. For all the genes three kb of upstream sequence was extracted and aligned separately, only one gene showed any significant alignment in the 5' putative control region. The lack of strong regulatory sequences could be an indication that the genes in this region are under relatively simple control as postulated for ERCC2 where a similar observation was made (Lamerdin et al, 1996; Hardison et al, 1997).

Hardison, R.C., Oeltjen, J. & Miller, W. Long human-mouse sequence alignments reveal novel regulatory elements: a reason to sequence the mouse genome. Genome Res 7, 959-66 (1997).

Lamerdin, J.E., Stilwagen, S.A., Ramirez, M.H., Stubbs, L. & Carrano, A.V. Sequence analysis of the ERCC2 gene regions in human, mouse, and hamster reveals three linked genes. Genomics 34, 399-409 (1996).

Schneider, T.D. & Stephens, R.M. Sequence logos: a new way to display consensus sequences. Nucleic Acids Research 18, 6097-100 (1990).

Smit, A.F. The origin of interspersed repeats in the human genome. Current Opinion In Genetics And Development 6, 743-8 (1996).

 


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