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

Abstract

Comparative genomics is a superior way to identify phylogenetically conserved features like genes or regions involved in gene regulation. The comparison of extended orthologous chromosomal regions should also reveal other characteristic traits essential for chromosome or gene function. In the present study we have sequenced and compared a region of conserved synteny from human chromosome 11p15.3 and mouse chromosome 7. In human, this region is known to contain several genes involved in the development of various disorders like Beckwith-Wiedemann overgrowth syndrome and other tumor diseases. Furthermore, in the neighboring chromosome region 11p15.5 extensive imprinting of genes has been reported which might extend to region 11p15.3. The analysis of approximately 730 kb in human and 620 kb in mouse led to the identification of eleven genes. All putative genes found in the mouse DNA were also present in the same order and orientation in the human chromosome. However, in the human DNA one putative gene of unknown function could be identified which is not present in the orthologous position of the mouse chromosome. The sequence similarity between human and mouse is higher in transcribed and exon regions than in non-transcribed segments. Dot plot analysis, however, reveals a surprisingly well-conserved sequence similarity over the entire analyzed region. In particular, the positions of CpG islands, short regions 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 segments of significantly different GC content exist as well in human as in the mouse. 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 average calculated for the complete human genome (one gene per 90 kb). The comparison of the number and distribution of repetitive elements shows that the proportion of human DNA made up by interspersed repeats (43.8%) is significantly higher than in the corresponding mouse DNA (30.1%). This partly explains why the human DNA is longer between the landmark genes used to define the orthologous positions in human and mouse.

Genes in a Refined Smith-Magenis Syndrome Critical Deletion Interval on Chromosome 17p11.2 and the Syntenic Region of the Mouse

“…The mouse genome sequence is ∼1.0 Mb with interspersed repeats accounting for only 27.6%. This ∼15% decrease in repetitive sequences in the mouse genome as compared to the human has also been observed in other genomic regions (Amid et al 2001).…”

“…The number, order, and orientation of all 17 genes in a gene-rich cluster at human 12p13 are conserved between humans and mice (Ansari-Lari et al 1998). Conservation between these two species was also shown for the distal 700 kb of the Cat eye syndrome (tetrasomy of 22q11.2) critical region and for human chromosome 11p15.3, both of which are gene-rich regions (Amid et al 2001;Footz et al 2001). According to the mosaic model of genomic evolution, different portions of the genome evolve at different rates (Koop 1995).…”

Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients

“…The role of ASCL4 in cellular function remains elusive. Therefore, comparative genomic sequencing did not reveal any function for this gene (32). ASCL4 expression did not satisfy the selection criteria of the present study; therefore, it was not selected for further investigation.…”

Gene expression profiling of primary cultures of ovarian epithelial cells identifies novel molecular classifiers of ovarian cancer

“…Here, we identified ST-5/HTS1 as a tumour suppressor gene downregulated in the majority of ovarian primary cultures derived from malignant tumours. ST-5 has been initially identified as a HeLa tumour suppression gene (Lichy et al, 1992;Amid et al, 2001). Interestingly, HeLa cells are derived from an uterine tumour, which suggests that ST-5 may be hormonally regulated.…”