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Genomic characterisation, chromosomal assignment and in vivo localisation of the canine high mobility group A1 (HMGA1) gene.

Beuing C, Soller JT, Muth M, Wagner S, Dolf G, Schelling C, Richter A, Willenbrock S, Reimann-Berg N, Winkler S, Nolte I, Bullerdiek J, Murua Escobar H - BMC Genet. (2008)

Bottom Line: By inducing DNA conformation changes the HMGA1 proteins indirectly influence the binding of various transcription factors and therefore effect the transcription regulation.Additionally, we evaluated a described canine HMGA1 exon 6 SNP in 55 Dachshunds.The performed characterisations will make comparative analyses of aberrations affecting the human and canine gene and proteins possible, thereby providing a basis for revealing mechanisms involved in HMGA1 related pathogenesis in both species.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinic for Small Animals and Research Cluster of Excellence REBIRTH, University of Veterinary Medicine Hanover, Bischofsholer Damm 15, 30173 Hanover, Germany. claudia.beuing@tiho-hannover.de

ABSTRACT

Background: The high mobility group A1 proteins (HMGA1a/HMGA1b) are highly conserved between mammalian species and widely described as participating in various cellular processes. By inducing DNA conformation changes the HMGA1 proteins indirectly influence the binding of various transcription factors and therefore effect the transcription regulation. In humans chromosomal aberrations affecting the HMGA1 gene locus on HSA 6p21 were described to be the cause for various benign mesenchymal tumours while high titres of HMGA1 proteins were shown to be associated with the neoplastic potential of various types of cancer. Interestingly, the absence of HMGA1 proteins was shown to cause insulin resistance and diabetes in humans and mice. Due to the various similarities in biology and presentation of human and canine cancers the dog has joined the common rodent animal model for therapeutic and preclinical studies. Accordingly, the canine genome was sequenced completely twice but unfortunately this could not solve the structure of canine HMGA1 gene.

Results: Herein we report the characterisation of the genomic structure of the canine HMGA1 gene consisting of 7 exons and 6 introns spanning in total 9524 bp, the in vivo localisation of the HMGA1 protein to the nucleus, and a chromosomal assignment of the gene by FISH to CFA12q11. Additionally, we evaluated a described canine HMGA1 exon 6 SNP in 55 Dachshunds.

Conclusion: The performed characterisations will make comparative analyses of aberrations affecting the human and canine gene and proteins possible, thereby providing a basis for revealing mechanisms involved in HMGA1 related pathogenesis in both species.

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Related in: MedlinePlus

Genomic structure of the canine HMGA1 gene. Detailed structure of the genomic organisation of the canine HMGA1 gene.
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Figure 2: Genomic structure of the canine HMGA1 gene. Detailed structure of the genomic organisation of the canine HMGA1 gene.

Mentions: The genomic structure of the canine HMGA1 gene consists in total of the 7 exons and 6 introns. Overall the canine HMGA1 gene spans 9524 bp. The exon/intron structure, size and the homologies to their human counterparts were analysed and defined (Figure 2, Table 1). The total identity to the corresponding human region is 62.8%. In detail, the identities of the exons vary between 74.6% and 97.8% to their human counterpart, while the introns show identities between 58.9% and 92.4% (for details see Table 1). The newly characterized sequences combined with the analyses performed in silico revealed that the exon 4, which exists in humans, is missing on genomic level in the canine genome. This exon 4 deletion also exists in the mouse genome and affects the respective mRNAs of both species in their 5' UTR. As the genomic characterization of the canine HMGA1 gene was not available when the exons were named previously, the numbering at that time was based on the respective human exon numbers as defined by Friedmann et al. [32]. Consequently, as it is now known that the canine genomic sequence is lacking an equivalent to human exon 4, the previously used canine exon numbering should be revised with the then named canine exon 5 now being canine exon 4 and so on (Figure 2, Table 1). However, a part of intron 2 remains unsequenced due to an extensive CG repeat which also exists in the human counterpart (90%CG), and only the number of nucleotides (311 bp) could be identified. The genomic sequences were submitted to the NCBI database (bankit1078465, bankit1078536, bankit1078968).


Genomic characterisation, chromosomal assignment and in vivo localisation of the canine high mobility group A1 (HMGA1) gene.

Beuing C, Soller JT, Muth M, Wagner S, Dolf G, Schelling C, Richter A, Willenbrock S, Reimann-Berg N, Winkler S, Nolte I, Bullerdiek J, Murua Escobar H - BMC Genet. (2008)

Genomic structure of the canine HMGA1 gene. Detailed structure of the genomic organisation of the canine HMGA1 gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2500044&req=5

Figure 2: Genomic structure of the canine HMGA1 gene. Detailed structure of the genomic organisation of the canine HMGA1 gene.
Mentions: The genomic structure of the canine HMGA1 gene consists in total of the 7 exons and 6 introns. Overall the canine HMGA1 gene spans 9524 bp. The exon/intron structure, size and the homologies to their human counterparts were analysed and defined (Figure 2, Table 1). The total identity to the corresponding human region is 62.8%. In detail, the identities of the exons vary between 74.6% and 97.8% to their human counterpart, while the introns show identities between 58.9% and 92.4% (for details see Table 1). The newly characterized sequences combined with the analyses performed in silico revealed that the exon 4, which exists in humans, is missing on genomic level in the canine genome. This exon 4 deletion also exists in the mouse genome and affects the respective mRNAs of both species in their 5' UTR. As the genomic characterization of the canine HMGA1 gene was not available when the exons were named previously, the numbering at that time was based on the respective human exon numbers as defined by Friedmann et al. [32]. Consequently, as it is now known that the canine genomic sequence is lacking an equivalent to human exon 4, the previously used canine exon numbering should be revised with the then named canine exon 5 now being canine exon 4 and so on (Figure 2, Table 1). However, a part of intron 2 remains unsequenced due to an extensive CG repeat which also exists in the human counterpart (90%CG), and only the number of nucleotides (311 bp) could be identified. The genomic sequences were submitted to the NCBI database (bankit1078465, bankit1078536, bankit1078968).

Bottom Line: By inducing DNA conformation changes the HMGA1 proteins indirectly influence the binding of various transcription factors and therefore effect the transcription regulation.Additionally, we evaluated a described canine HMGA1 exon 6 SNP in 55 Dachshunds.The performed characterisations will make comparative analyses of aberrations affecting the human and canine gene and proteins possible, thereby providing a basis for revealing mechanisms involved in HMGA1 related pathogenesis in both species.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clinic for Small Animals and Research Cluster of Excellence REBIRTH, University of Veterinary Medicine Hanover, Bischofsholer Damm 15, 30173 Hanover, Germany. claudia.beuing@tiho-hannover.de

ABSTRACT

Background: The high mobility group A1 proteins (HMGA1a/HMGA1b) are highly conserved between mammalian species and widely described as participating in various cellular processes. By inducing DNA conformation changes the HMGA1 proteins indirectly influence the binding of various transcription factors and therefore effect the transcription regulation. In humans chromosomal aberrations affecting the HMGA1 gene locus on HSA 6p21 were described to be the cause for various benign mesenchymal tumours while high titres of HMGA1 proteins were shown to be associated with the neoplastic potential of various types of cancer. Interestingly, the absence of HMGA1 proteins was shown to cause insulin resistance and diabetes in humans and mice. Due to the various similarities in biology and presentation of human and canine cancers the dog has joined the common rodent animal model for therapeutic and preclinical studies. Accordingly, the canine genome was sequenced completely twice but unfortunately this could not solve the structure of canine HMGA1 gene.

Results: Herein we report the characterisation of the genomic structure of the canine HMGA1 gene consisting of 7 exons and 6 introns spanning in total 9524 bp, the in vivo localisation of the HMGA1 protein to the nucleus, and a chromosomal assignment of the gene by FISH to CFA12q11. Additionally, we evaluated a described canine HMGA1 exon 6 SNP in 55 Dachshunds.

Conclusion: The performed characterisations will make comparative analyses of aberrations affecting the human and canine gene and proteins possible, thereby providing a basis for revealing mechanisms involved in HMGA1 related pathogenesis in both species.

Show MeSH
Related in: MedlinePlus