Genomic structural variants, including translocations, inversions, insertions, deletions, and duplications, are challenging to be reliably detected by traditional genomic technologies. In particular, balanced translocations and inversions can neither be identified by microarrays since they do not alter chromosome copy numbers, nor by short-read sequencing because of the unmappability of short reads against repetitive genomic regions. The precise localization of breakpoints is vital for exploring genetic causes in patients with balanced translocations or inversions. Long-read sequencing techniques may detect these structural variants in a more direct, efficient, and accurate manner. Here, we performed whole-genome, long-read sequencing using the Oxford Nanopore GridION sequencer to detect breakpoints in six balanced chromosome translocation carriers and one inversion carrier. The results showed that all the breakpoints were consistent with the karyotype results with only~10× coverage. Polymerase chain reaction (PCR) and Sanger sequencing confirmed 8 out of 14 breakpoints; however, other breakpoint loci were slightly missed since they were either in highly repetitive regions or pericentromeric regions. Some of the breakpoints interrupted normal gene structure, and in other cases, micro-deletions/insertions were found just next to the breakpoints. We also detected haplotypes around the breakpoint regions. Our results suggest that longread, whole-genome sequencing is an ideal strategy for precisely localizing translocation breakpoints and providing haplotype information, which is essential for medical genetics and preimplantation genetic testing.
Structural variants (SVs) in genomes, including translocations, inversions, insertions, deletions and duplications, remain difficult to be detected reliably by traditional genomic technologies. In particular, balanced translocations and inversions cannot be detected by microarrays since they do not alter chromosome copy numbers; they cannot be reliably detected by short-read sequencing either, since many breakpoints are located within repetitive regions of the genome that are unmappable by short reads. However, the detection and the precise localization of breakpoints at the nucleotide level are important to study the genetic causes in patients carrying balanced translocations or inversions. Long-read sequencing techniques, such as the Oxford Nanopore Technology (ONT), may detect these SVs in a more direct, efficient and accurate manner. In this study, we applied whole-genome long-read sequencing on the Oxford Nanopore GridION sequencer to detect the breakpoints from 6 carriers of balanced translocations and one carrier of inversion, where SVs had initially been detected by karyotyping at the chromosome level. The results showed that all the balanced translocations were detected with ~10X coverage and were consistent with the karyotyping results. PCR and Sanger sequencing confirmed 8 of the 14 breakpoints to single base resolution, yet other breakpoints cannot be refined to single-base due to their localization at highly repetitive regions or pericentromeric regions, or due to the possible presence of local deletions/duplications. Our results indicate that low-coverage whole-genome sequencing is an ideal tool for the precise localization of most translocation breakpoints and may provide haplotype information on the breakpoint-linked SNPs, which may be widely applied in SV detection, therapeutic monitoring, assisted reproduction technology (ART) and preimplantation genetic diagnosis (PGD).
Global climate change has become a major threat to biodiversity, posing severe challenges to species conservation. This is particularly true for species such as Horsfieldia tetratepala that have extremely small populations in the wild. Little is known about the species distribution of H. tetratepala in the current climate, as well as how that will change with potential future climates. The key environmental factors that influence its expansion, especially its habitat sustainability and its potential to adapt to climate change, are also unknown, though such information is vital for the protection of this endangered species. Based on six climate factors and 25 species distribution points, this study used the maximum entropy model (MaxEnt) to simulate the potential distribution for H. tetratepala in three periods (current, 2050s, and 2070s), and to investigate the changes in distribution patterns and the main environmental factors affecting species distribution. The modeling results show that the most important bioclimatic variables affecting H. tetratepala were precipitation of the warmest quarter (Bio_18) and temperature seasonality (Bio_4). The suitable areas for H. tetratepala will gradually be lost in Yunnan but will be generally offset in the northeastward direction, expanding in Hainan, Guangzhou, and Taiwan provinces under the future climate conditions. Therefore, we recommend protecting the habitats of H. tetratepala in Yunnan and strengthening the in-depth species investigation and monitoring in areas (Hainan, Guangzhou, and Taiwan) where no related reports of H. tetratepala have been reported. The results improve our understanding of this species’ response under the changing climate and benefit strategies for its conservation.
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