Limits...
The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders.

De Vilder EY, Hosen MJ, Vanakker OM - Biomed Res Int (2015)

Bottom Line: The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders.While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them.In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases.

View Article: PubMed Central - PubMed

Affiliation: Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium ; Department of Ophthalmology, Ghent University Hospital, 9000 Ghent, Belgium.

ABSTRACT
The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as chronic kidney disease or cardiovascular disorders have been linked to the ABCC6 gene. While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them. To gain more insights, multiple approaches are being used including next-generation sequencing, computational methods, and various "omics" technologies. Much effort is made to place the vast amount of data that is gathered in an integrated system-biological network; the involvement of ABCC6 in common disorders provides a good view on the wide implications and potential of such a network. In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the multistep process starting from a rare Mendelian disease such as PXE and subsequent identification of the causal gene(s). From then, a combination of technological approaches is performed in several model systems to gain insights into cellular signaling. This knowledge can already be of relevance for common disorders, which show an overlap with the phenotype of the rare disease, but can also be used for development of innovative treatments, which benefit patients of both orphan and complex disorders [20, 21, 46–54].
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4555454&req=5

fig4: Schematic representation of the multistep process starting from a rare Mendelian disease such as PXE and subsequent identification of the causal gene(s). From then, a combination of technological approaches is performed in several model systems to gain insights into cellular signaling. This knowledge can already be of relevance for common disorders, which show an overlap with the phenotype of the rare disease, but can also be used for development of innovative treatments, which benefit patients of both orphan and complex disorders [20, 21, 46–54].

Mentions: Over the past years, the field of genetics and genomics has experienced a revolution in the way we think about biological mechanisms and cellular signaling, which for an important part is due to remarkable technological advances. Increasingly, scientific exploration of diseases uses a diverse repertory of approaches to gain insights into the biology underlying a specific disease or protein. These approaches include next-generation sequencing, expression assays, proteomics, transcriptomics, metabolomics, network analysis, and computational biology. Besides the challenges of interpreting the large datasets that are gathered by some of these high-throughput technologies, the integration of all this knowledge into a unified system-biological structure is particularly challenging (Figure 4).


The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders.

De Vilder EY, Hosen MJ, Vanakker OM - Biomed Res Int (2015)

Schematic representation of the multistep process starting from a rare Mendelian disease such as PXE and subsequent identification of the causal gene(s). From then, a combination of technological approaches is performed in several model systems to gain insights into cellular signaling. This knowledge can already be of relevance for common disorders, which show an overlap with the phenotype of the rare disease, but can also be used for development of innovative treatments, which benefit patients of both orphan and complex disorders [20, 21, 46–54].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555454&req=5

fig4: Schematic representation of the multistep process starting from a rare Mendelian disease such as PXE and subsequent identification of the causal gene(s). From then, a combination of technological approaches is performed in several model systems to gain insights into cellular signaling. This knowledge can already be of relevance for common disorders, which show an overlap with the phenotype of the rare disease, but can also be used for development of innovative treatments, which benefit patients of both orphan and complex disorders [20, 21, 46–54].
Mentions: Over the past years, the field of genetics and genomics has experienced a revolution in the way we think about biological mechanisms and cellular signaling, which for an important part is due to remarkable technological advances. Increasingly, scientific exploration of diseases uses a diverse repertory of approaches to gain insights into the biology underlying a specific disease or protein. These approaches include next-generation sequencing, expression assays, proteomics, transcriptomics, metabolomics, network analysis, and computational biology. Besides the challenges of interpreting the large datasets that are gathered by some of these high-throughput technologies, the integration of all this knowledge into a unified system-biological structure is particularly challenging (Figure 4).

Bottom Line: The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders.While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them.In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases.

View Article: PubMed Central - PubMed

Affiliation: Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium ; Department of Ophthalmology, Ghent University Hospital, 9000 Ghent, Belgium.

ABSTRACT
The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as chronic kidney disease or cardiovascular disorders have been linked to the ABCC6 gene. While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them. To gain more insights, multiple approaches are being used including next-generation sequencing, computational methods, and various "omics" technologies. Much effort is made to place the vast amount of data that is gathered in an integrated system-biological network; the involvement of ABCC6 in common disorders provides a good view on the wide implications and potential of such a network. In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases.

No MeSH data available.


Related in: MedlinePlus