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61.
Fangyan Yu Ka Wai Leong Alexander Makrigiorgos Viktor A Adalsteinsson Ioannis Ladas Kimmie Ng Harvey Mamon G Mike Makrigiorgos 《Nucleic acids research》2021,49(4):e24
Sensitive detection of microsatellite instability (MSI) in tissue or liquid biopsies using next generation sequencing (NGS) has growing prognostic and predictive applications in cancer. However, the complexities of NGS make it cumbersome as compared to established multiplex-PCR detection of MSI. We present a new approach to detect MSI using inter-Alu-PCR followed by targeted NGS, that combines the practical advantages of multiplexed-PCR with the breadth of information provided by NGS. Inter-Alu-PCR employs poly-adenine repeats of variable length present in every Alu element and provides a massively-parallel, rapid approach to capture poly-A-rich genomic fractions within short 80–150bp amplicons generated from adjacent Alu-sequences. A custom-made software analysis tool, MSI-tracer, enables Alu-associated MSI detection from tissue biopsies or MSI-tracing at low-levels in circulating-DNA. MSI-associated indels at somatic-indel frequencies of 0.05–1.5% can be detected depending on the availability of matching normal tissue and the extent of instability. Due to the high Alu copy-number in human genomes, a single inter-Alu-PCR retrieves enough information for identification of MSI-associated-indels from ∼100 pg circulating-DNA, reducing current limits by ∼2-orders of magnitude and equivalent to circulating-DNA obtained from finger-sticks. The combined practical and informational advantages of inter-Alu-PCR make it a powerful tool for identifying tissue-MSI-status or tracing MSI-associated-indels in liquid biopsies. 相似文献
62.
Pall Hersteinsson Gudmundur Georgsson Stefán Adalsteinsson Eggert Gunnarsson 《Polar Biology》2007,30(8):1047-1058
We describe the manifestations and occurrence of hypotrichosis in arctic foxes and compare it to the Samson character in red
foxes. During 1979–2005, we collected carcasses of both normal and hypotrichotic arctic foxes from foxhunters in Iceland for
macroscopic and microscopic examination and study of demography. We obtained live pups for breeding and transmission experiments
in captivity during 1985–1992. Placental scar counts showed that hypotrichotic vixens were more fertile than normal vixens
and generally all their pups were hypotrichotic. Fertility in hypotrichotic vixens was positively correlated with winter air
temperature but not in normal vixens. Hypotrichotic males were less likely to breed than normal males and probably had a higher
mortality rate than either hypotrichotic females or normal foxes. Hypotrichosis can be transmitted between adult foxes. Microscopic
examination revealed prominent chronic inflammation of the dermis in hypotrichotic specimens, degenerative changes, vacuolisation
and necrosis of hair follicles. Hypotrichosis persists in coastal areas with mild winters and may become more common with
global warming. 相似文献