Identifying Missing Heritability and Genetic Etiologies of Undiagnosed Fetuses and Children with Multiple Congenital Anomalies by Sequencing

Professor CHOY Kwong-wai, Richard

Department of Obstetrics and Gynaecology, CUHK

Herein, we propose: (1) Investigate clinically significant genome-wide variants using LRS in a cohort with multiple congenital anomalies and suspicion of a genetic etiology previously unresolved by WGS, (2) Compare the differences in the spectrum of variants called by long-read and short-read approaches to investigate concordance, sensitivities and specificities of variant detection. The sequencing characteristics of long-read sequencing will also be investigated. Through this study, we aim to provide the diagnostic utility of long-read sequencing in a unique cohort previously unresolved by WGS and to discover the underlying causative genetic factors in individuals with undiagnosed and unexplained MCA so as to maximize clinical management, benefits prognosis and reproductive options to patients.