About this Research Topic
For a long time, investigations in human genetics have focused solely on protein-coding genes. As one of the main outcomes of the Human Genome Project, it has become clear that the majority of DNA sequences in humans does not directly encode for proteins. Many of these lie outside of coding exons and are now known to be involved in the regulation of gene expression. The dissection of the non-coding genome is also becoming the research focus of clinical genetics, as mutations in protein-coding regions of genes account for only 30-50% of genetic disorders and thus, there is still a large fraction of missing heritability, which remains undiscovered.
Despite progress in the last decade, our current understanding of the non-coding genome and its functional annotation is still rather in its early stages and far from completely understood. This hinders the routine implementation of whole genome sequencing in a clinical setting, as it is impossible to assign a functional role of most variants outside of coding exons that can be found in the human population. Recent technological advances, such as high-throughput massively-parallel-reporter assays, CRISPR-Cas9 based screens, and computational approaches promise to further delineate the functional relevance of genetic variation in the non-coding genome. This will have major implications for both the way we can decipher molecular mechanisms involved during normal development as well as the pathogenesis of genetic disorders.
The goal of this Research Topic is to increase our understanding and highlight the role of non-coding regulatory elements involved in human development and disease, especially focusing on brain development, neurocristopathies and embryonic axis elongation/spinal cord development defects.
Papers submitted within this Topic should address relevant questions regarding the role and functional characterization of non-coding regulatory elements, such as enhancers, silencers, and elements involved in the 3D chromosomal organization, during both normal embryonic development and human diseases. We welcome submissions covering any of the following subjects:
- Original research and review papers on non-coding regulatory elements involved in normal embryonic development (including non-human animal models), in particular, but not limited, to brain development, neurocristopathies and embryonic axis elongation/spinal cord development defects,
- Original research and review papers on variants in non-coding regulatory elements involved in human disease,
- Original research and review papers describing novel technological advances that can lead to an improved understanding of variation in non-coding regulatory elements; this can include but is not limited to novel types of massively-parallel-reporter systems, CRISPR-Cas9 based screens or computational approaches.
Keywords: Non-coding cis-regulatory elements, enhancer, functional genomics, clinical genetics, congenital anomalies, birth defects
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.