Abstract
Rare diseases affect more than 350 million people worldwide. Of those, more than 80 percent are of genetic origins. The diseases are severe, frequently cause congenital deformities, and rapidly deteriorated. Diagnosis of rare diseases is complicated and could take up to 8 years. Long-lasting diagnostic procedures mean wasting time and opportunity of medical personals to treat other patients, several laboratory tests, repeated hospital admission, and unnecessary treatment. These deteriorate the physical, psychological, and economic conditions of the patients and their families. To date, a vast number of patients with rare diseases lack an opportunity to access precise or correct diagnosis and treatment. Previous studies have demonstrated that more than 52 million children worldwide are died before the age of 5 years due to rare diseases. These show that urgent implementation must be employed to tackle undiagnosed rare diseases. With the Next Generation Sequencing (NGS) technology including whole exome sequencing (WES) and whole genome sequencing (WGS), up to 50 percent of rare diseases have been successfully diagnosed in the last 10 years. NGS has improved disease prevention, prenatal diagnosis, prognosis, and pharmacogenomics. Although WES/ WGS which are the short-read technologies (< 150bp nucleotides) have increased diagnostic yield of rare diseases, the yield is limited at 50 percent of cases. One founding reason is that short-read WGS is unable to diagnose certain molecular pathologies including structural mutation, inversion, and repeats. Our research team therefore has utilized a recent sequencing technology “long-read sequencing”, which can sequence more than 20,000 nucleotides in length, to do whole genome sequencing for 60 individuals comprising patients and their parents. We successfully performed the high-molecular weight DNA extraction, checked the DNA quality, optimized sequencing condition, analysed the genome information and sent the genome data to NSTDA for the establishment of long-read genome database. We have found that long-read sequencing could identify the diversity of genomics including single nucleotide variation (SNV), in/del (insertion/deletion), structural variation (SV), and copy number variation (CNV) which were unable to be identified by short-read sequencing. During the process which required short-read exome/genome sequencing and subsequently long-read sequencing, we could published 22 articles in international academic peer-review journals. The database will be beneficial to genomic research and medical service in the era of genomics medicine. The long-read WGS has a great potential to be the new standard in the era of precision medicine when personalized therapy can benefit the patient, family, society, and economy.
