Genetic Complexity of the Human Genome in Health and Disease: Basic Concepts
A. Athanassiadou
- Vol. 23, Iss: 2, pp 113-120
Reads0
Chats0
TLDR
The great variation of genome sequence and regulatory elements of the genome architecture are exploited in studies of genome-wide association with disease, in the framework of Precision Medicine and in general of Genomic Medicine.Abstract:
Determination of the DNA sequence of the human genome, revealing extensive genetic variation, and the mapping of the genes and the various regulatory elements of genome function within the genomic DNA, has revolutionized the way we view the states of health and disease in our time. Genetic complexity of the genome is manifested on different levels. The first level refers to the expression of protein coding genes, as regulated by their individual promoter in linear proximity. The next level of genetic complexity involves long distance action by far away enhancers, interacting with promoters through DNA looping. This 3dimensional (3D) regulation is further developing by chromosome folding into the so called transcription factories, for fully physiological expression. Chromosome folding, mediated by specific genetic elements – insulators – is adding to the genetic complexity by facilitating movements of chromatin of specific genomic regions – the so-called topologically associated domains (TAD) in support of transcription and other cellular functions. Further genetic complexity has emerged with the finding that over 75% of the genome is transcribed and except of the coding genes, a plethora of RNA transcripts are produced – the non-coding RNA – that has important regulatory roles in the gene expression context. The great variation of genome sequence and regulatory elements of the genome architecture are exploited in studies of genome-wide association with disease, in the framework of Precision Medicine and in general of Genomic Medicine.read more
Citations
More filters
A bioinformatics approach for precision medicine off-label drug drug selection among triple negative breast cancer patients
TL;DR: A personalized medicine knowledge base is constructed by integrating various cancer drugs, drug-target database, and knowledge sources for the proper cancer drugs and their target selections by analyzing the 85 triple negative breast cancer patient data in the Cancer Genome Altar.
References
More filters
Journal ArticleDOI
Capturing Chromosome Conformation
TL;DR: Using the yeast Saccharomyces cerevisiae, this work could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis and found that chromatin is highly flexible throughout.
Journal ArticleDOI
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions
Darío G. Lupiáñez,Darío G. Lupiáñez,Katerina Kraft,Katerina Kraft,Verena Heinrich,Peter Krawitz,Peter Krawitz,Francesco Brancati,Eva Klopocki,Denise Horn,Hülya Kayserili,John M. Opitz,Renata Laxova,Fernando Santos-Simarro,Fernando Santos-Simarro,Brigitte Gilbert-Dussardier,Lars Wittler,Marina Borschiwer,Stefan A. Haas,Marco Osterwalder,Martin Franke,Martin Franke,Bernd Timmermann,Jochen Hecht,Jochen Hecht,Malte Spielmann,Malte Spielmann,Axel Visel,Axel Visel,Axel Visel,Stefan Mundlos,Stefan Mundlos +31 more
TL;DR: The results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome.
Roles for MicroRNAs in Conferring Robustness to Biological Processes
TL;DR: In this paper, the authors discuss examples and principles of microRNAs that contribute to robustness in animal systems, including reinforcement of transcriptional programs and attenuation of aberrant transcripts.
Journal ArticleDOI
Active genes dynamically colocalize to shared sites of ongoing transcription.
Cameron S. Osborne,Lyubomira Chakalova,Karen E. Brown,David R. F. Carter,David R. F. Carter,Alice Horton,Emmanuel Debrand,Beatriz Goyenechea,Jennifer A. Mitchell,Susana Lopes,Susana Lopes,Wolf Reik,Peter Fraser +12 more
TL;DR: It is shown that, during transcription in vivo, distal genes colocalize to the same transcription factory at high frequencies.
Journal ArticleDOI
Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data
TL;DR: Several types of statistical and computational approaches that have recently been developed to analyse chromatin interaction data are described.
Related Papers (5)
How is the Human Genome Project doing, and what have we learned so far?
Mark S. Guyer,Francis S. Collins +1 more