Recently, next-generation sequencing (NGS) has been being rapidly implemented into genetic screening and diagnostic settings. At present, this mainly involves whole genome sequencing (WGS) and whole exome sequencing (WES), but the cost of WGS is still high, and WES filters out a large number of non-coding regions with important functions. Here, AluScan sequencing which amplifies inter-Alu regions in the human genome using Alu consensus sequence-based PCR primers for subsequent NGS, is applied to understand the effects of genomic variations in two diseases: trichloroethylene (TCE) induced occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) and liver cancer.

TCE induced OMDT is a systemic skin disorder accompanied by liver dysfunction in workers occupationa...[ Read more ]

Recently, next-generation sequencing (NGS) has been being rapidly implemented into genetic screening and diagnostic settings. At present, this mainly involves whole genome sequencing (WGS) and whole exome sequencing (WES), but the cost of WGS is still high, and WES filters out a large number of non-coding regions with important functions. Here, AluScan sequencing which amplifies inter-Alu regions in the human genome using Alu consensus sequence-based PCR primers for subsequent NGS, is applied to understand the effects of genomic variations in two diseases: trichloroethylene (TCE) induced occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) and liver cancer.

TCE induced OMDT is a systemic skin disorder accompanied by liver dysfunction in workers occupationally exposed to TCE. Coverage of 14.54 Mb genome regions with at least four-fold depth across OMDT patients and controls was achieved with AluScan sequencing. Single-nucleotide polymorphism (SNP) rs941960 located in the CCBL1 gene coding for cysteine conjugate-beta lyase, and copy number gains in CYP2C9 and CYP3A4 were identified as plausible causal factors. These results indicated the importance of metabolic abnormality in OMDT and supported the use of AluScan as an approach for discovering disease-related variations.

Liver cancer is the second leading cause of cancer-related death worldwide. Using 110 WGS data of tumor-blood pairs from Japanese patients with liver cancer, both high LOH% and S1% where signature S1 was one of two mutation signatures decomposed from the SNV profile was associated with poor prognosis. When these indices were delineated using in silico-derived mutation sets representing WES and AluScan, the associations remained significant in the order WGS-WES < WGS < WGS-AluScan for LOH%, and WGS-WES < WGS-AluScan < WGS for S1%. The result suggested LOH% as a prognostic marker that can be employed for liver cancer subtyping and that can be use with AluScan as the sequencing platform without loss of power.