About this Research Topic
Third generation sequencing technologies can produce substantially longer reads than second generation, sequencing up to 1Mb thus leading to more accurate assembly of diploid genomes and to detection of the full spectrum of human genetic variation. Long read sequencing data analysis was shown to lead to clearer understanding of more complex forms of genetic variation, including large insertions and deletions and in identifying complex structural variation including rearrangements in a haploid genome. Furthermore, long read sequencing methods read through repetitive sequence elements. Long read sequencing can also facilitate haplotype analysis. It is interesting to note that new sequencing techniques can detect base modifications e.g. methylation without using additional sequencing reactions.
Determining the functional significance of DNA nucleotide variants can be complex. Furthermore, there is increasing evidence for cell and tissue specific differences in RNA splicing. It therefore becomes increasingly important to consider these tissue specific differences in transcription in relation to the specific organs and cell types impacted in a specific disease and isoform diversity when interpreting functional significance of DNA sequence data. Long read sequencing of RNA can facilitate analysis of different mRNA isoforms derived from a specific gene transcripts.
Accessibility of disease relevant tissues for diagnostic purposes can present a barrier to gene and transcript analysis, however there is growing information on the presence of cell-free DNA and mRNA in specific body fluids. Cell-free DNA analysis is of growing importance in cancer studies and in prenatal diagnosis
It has also become clearer that more conceptions of genetic disease origins should be considered. These include digenic inheritance and possibly the joint interactions and involvement of pathogenic defects in a protein-coding gene along with alterations in variants in the non-protein coding genome regions, the regulatory genome.
In this Research Topic we seek to recruit manuscripts that present information utilizing some of these new approaches, including long read sequence analysis, transcriptome analysis or cell free nucleic analysis in determining the genomic and molecular basis of single genetic and genomic disorders including cancer.
Keywords: Third Generation Sequencing, transcriptome, cell-free nucleic acids, genomic diseases, long read sequence analysis
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