Application of Next Generation Sequencing in Laboratory Medicine

The rapid development of next-generation sequencing (NGS) technology, including advances in sequencing chemistry, sequencing technologies, bioinformatics, and data interpretation, has facilitated its wide clinical application in precision medicine. This review describes current sequencing technologies, including short- and long-read sequencing technologies, and highlights the clinical application of NGS in inherited diseases, oncology, and infectious diseases. We review NGS approaches and clinical diagnosis for constitutional disorders; summarize the application of U.S. Food and Drug Administration-approved NGS panels, cancer biomarkers, minimal residual disease, and liquid biopsy in clinical oncology; and consider epidemiological surveillance, identification of pathogens, and the importance of host microbiome in infectious diseases. Finally, we discuss the challenges and future perspectives of clinical NGS tests.

9p subtelomere deletion: pathogenic mutation or normal variant? / 北京大学学报(医学版)

We report an apparently benign familial 9p subtelomere deletion identified using chromosome-arm-specific subtelomere probes in a patient with multiple congenital anomalies. Our experience demonstrated that the discovery of a subtelomeric deletion and/or duplication does not always guarantee the identification of the etiology for the patient's phenotype and a positive finding with subtelomere probes should always be followed by parental study with the same probe in order to distinguish a disease causing alteration from a benign familial polymorphism.

Advanced molecular and cytogenetic technologies in birth defect diagnosis and prevention / 北京大学学报(医学版)

SUMMARY Fluorescence in situ hybridization (FISH) has become an important diagnostic tool as an adjunct to classical cytogenetics. FISH utilizes DNA probes comprised of specific nucleic acid sequences tagged with fluorescent molecules to identify the number and location of specific DNA sequences in human cells. These probes can be used to determine various numerical and structural chromosomal aberrations, in many cases, gene dosage and/or structure alterations. Chromosomal abnormalities are responsible for a considerable number of birth defects, and more than 50% of spontaneous abortions. These numbers have been significantly higher since the advent of FISH technology that allows the detection of submicroscopic chromosome alterations. The clinic application of FISH technology in postnatal, prenatal, and preimplantation diagnoses has been playing an important role in the diagnosis and prevention of birth defects. As new technologies evolve, more and more new FISH techniques - such as subtelomeric FISH, multicolor FISH (M-FISH), comparative genomic hybridization (CGH), and microarray - are used in clinical diagnoses, the role of FISH technology in both research and clinical aspects of birth defects will surely continue to expand.