Directional genomic hybridization for chromosomal inversion discovery and detection.

摘要: Chromosomal rearrangements are a source of structural variation within the genome that figure prominently in human disease, where importance translocations and deletions is well recognized. In principle, inversions—reversals orientation DNA sequences chromosome—should have similar detrimental potential. However, study inversions has been hampered by traditional approaches used for their detection, which not particularly robust. Even with significant advances whole approaches, changes absolute remain difficult to detect routinely. Consequently, our understanding still surprisingly limited, as appreciation frequency involvement disease. Here, we introduce directional genomic hybridization methodology chromatid painting—a new way looking at features genome—that can be employed high resolution on cell-by-cell basis, demonstrate its basic capabilities genome-wide discovery targeted detection inversions. Bioinformatics enabled development sequence- strand-specific probe sets, when coupled single-stranded hybridization, greatly improved ease inversion detection. We highlight examples far-ranging applicability this cytogenomics-based approach, include confirmation alignment database evidence individuals themselves share sequence directionality, use comparative evolutionary studies any species whose sequenced. addition applications related mechanistic studies, information obtainable strategies may ultimately enable novel gene discovery, thereby benefitting diagnosis treatment variety disease states disorders including cancer, autism, idiopathic infertility.