Abstract
Many genes important during early development in vertebrates are regulated by sequences located at large distances from the protein coding region. Clues to the location of these long-range gene-regulatory elements can be obtained from comparing genomic sequences of evolutionarily distant species such as the mouse and human. However, identifying them functionally remains a major challenge. Analysis of distal regulatory sequences is important not only for a complete understanding of regulation of the gene in specific tissues, but also for exploring mechanisms and possible therapeutic strategies for diseases linked to variations in those sequences. Polymorphisms existing in far away regulatory sequences that are linked statistically to a disease can be associated with a gene only when such sequences are functionally implicated in regulating the expression of that gene. The mechanistic pathway that connects the disease to the malfunction of the gene can then be identified, and possible therapeutic interventions explored. A strategy that uses transgenic mice developed with a GFP-reporter gene tagged BAC clone to functionally identify such long-range regulatory sequences in the cardiac specific Nkx2-5 gene is illustrated. A combinatorial approach using the full length Nkx2-5 GFP-BAC and several of its truncations, chosen on the basis of cross-species genomic sequence alignment of highly conserved non-coding DNA, as transgenes helped delimit the boundaries of transcriptional regulation to sequences 27 kb upstream of the Nkx2- 5 gene. Identifying sequences involved in the regulation of genes distant to them are discussed in view of their potential for exploring mechanistic pathways for disease and possible therapeutic interventions.
Keywords: Polymorphisms, BAC clone, P1-derived artificial chromosomes, post genome-sequencing, locP Transposons, Nkx2-5 gene
Call for Papers in Thematic Issues
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Deep learning in Single Cell Analysis
The field of biology is undergoing a revolution in our ability to study individual cells at the molecular level, and to integrate data from multiple sources and modalities. This has been made possible by advances in technologies for single-cell sequencing, multi-omics profiling, spatial transcriptomics, and high-throughput imaging, as well as ...read more
New insights on Pediatric Tumors and Associated Cancer Predisposition Syndromes
Because of the broad spectrum of children cancer susceptibility, the diagnosis of cancer risk syndromes in children is rarely used in direct cancer treatment. The field of pediatric cancer genetics and genomics will only continue to expand as a result of increasing use of genetic testing tools. It's possible that ...read more
Related Journals
Related Books
.jpeg)
1st Biotechnology World Congress - 2012
Decolorization by Thanatephorus Cucumeris Dec 1
Industrial Applications of Soil Microbes
The Future of Agriculture: IoT, AI and Blockchain Technology for Sustainable Farming
Handbook of Integrated Weed Management for Major Field Crops
Practical Biochemistry
Anticancer Drugs Sourced from Marine Life
Opportunities for Biotechnology Research and Entrepreneurship
Diseases of Ornamental, Aromatic and Medicinal Plants
Diabetes and Breast Cancer: An Analysis of Signaling Pathways
1