Final Report Summary - HUCNC (Conserved Non-Coding Sequences; function, variability and phenotypic consequences)
The sequence of individual human genomes results in millions of nucleotide differences and other variations from the reference sequence. A major challenge in Genomic Medicine is to understand which of these variants are pathogenic (i.e. relate to phenotypes) and which are neutral (i.e. do not contribute to the phenotype variability). This challenge is daunting since the function of only a small fraction (1.5%) of the human genome is known, while the vast majority of the functional nucleotides have not yet been characterized.
The overall objective of this project was to functionally understand the non-coding (conserved and non-conserved) fraction of the genome, appreciate the functional consequences of genomic variation in gene expression (coding and non-coding) and epigenetic marks, and to begin to understand the global consequences of transcriptional dysregulation.
The most important conclusions of the research supported by this ERC grant were: 1) the human transcriptone contains thousands of non-coding transcripts; 2) the epigenetic DNA methylation is partially controlled by the genome variability; 3) the discovery of functional variation in the human genome outside of protein-coding genes; 4) the discovery of the genomic control of LincRNAs; 5) the discovery of domains of gene expression dysregulation in trisomy 21; 6) the development of computer algorithms for the analysis of DNA-Seq data and the establishment of high-throughput sequencing as the preferred approach to identify pathogenic variants.
The results from this research have significantly contributed to the understanding of the functional variability of the genome and thus enhanced the knowledge infrastructure necessary for the development and implementation of Genomic Medicine.
The overall objective of this project was to functionally understand the non-coding (conserved and non-conserved) fraction of the genome, appreciate the functional consequences of genomic variation in gene expression (coding and non-coding) and epigenetic marks, and to begin to understand the global consequences of transcriptional dysregulation.
The most important conclusions of the research supported by this ERC grant were: 1) the human transcriptone contains thousands of non-coding transcripts; 2) the epigenetic DNA methylation is partially controlled by the genome variability; 3) the discovery of functional variation in the human genome outside of protein-coding genes; 4) the discovery of the genomic control of LincRNAs; 5) the discovery of domains of gene expression dysregulation in trisomy 21; 6) the development of computer algorithms for the analysis of DNA-Seq data and the establishment of high-throughput sequencing as the preferred approach to identify pathogenic variants.
The results from this research have significantly contributed to the understanding of the functional variability of the genome and thus enhanced the knowledge infrastructure necessary for the development and implementation of Genomic Medicine.