Comparative genomic sequencing reveals a strikingly similar architecture of a conserved syntenic region on human chromosome 11p15.3 (including gene ST5) and mouse chromosome 7

Comparative genomics is a superior way to identify phylogenetically conserv ed features like genes or regions involved in gene regulation. The comparis on of extended orthologous chromosomal regions should also reveal other cha racteristic traits essential for chromosome or gene function. In the presen t study we have sequenced and compared a region of conserved synteny from h uman chromosome 11p15.3 and mouse chromosome 7. In human, this region is kn own to contain several genes involved in the development of various disorde rs like Beckwith-Wiedemann overgrowth syndrome and other tumor diseases. Fu rthermore, in the neighboring chromosome region 11p15.5 extensive imprintin g of genes has been reported which might extend to region 11p15.3. The anal ysis of approximately 730 kb in human and 620 kb in mouse led to the identi fication of eleven genes. All putative genes found in the mouse DNA were al so present in the same order and orientation in the human chromosome. Howev er, in the human DNA one putative gene of unknown function could be identif ied which is not present in the orthologous position of the mouse chromosom e. The sequence similarity between human and mouse is higher in transcribed and exon regions than in nontranscribed segments. Dot plot analysis, howev er, reveals a surprisingly well-conserved sequence similarity over the enti re analyzed region. In particular, the positions of CpG islands, short regi ons of very high GC content in the 5' region of putative genes. are similar in human and mouse. With respect to base composition, two distinct segment s of significantly different GC content exist as well in human as in the mo use. With a GC content of 45% the one segment would correspond to "isochore H1" and the other segment (39% GC in human, 40% GC in mouse) to "isochore L1/L2". The gene density (one gene per 66 kb) is slightly higher than the a verage calculated for the complete human genome (one gene per 90 kb). The c omparison of the number and distribution of repetitive elements shows that the proportion of human DNA made up by interspersed repeats (43.8%) is sign ificantly higher than in the corresponding mouse DNA (30.1%). This partly e xplains why the human DNA is longer between the landmark genes used to defi ne the orthologous positions in human and mouse. Copyright (C) 2001 S. Karg er AG, Basel.