CHIPS for genetic testing to improve a regional clinical genetic service

Abstract

In current practice of clinical genetics, molecular diagnosis has become more widely used than ever before. DNA diagnosis is important for appropriate medical care of the patient, and proper genetic counseling to the family. However, genetic testing of orphan disease cannot always be performed easily. In multiple congenital anomalies (MCA) syndromes by monogenic cause, the broad mutational spectrum and large size of responsible genes often make molecular diagnosis expensive and cumbersome. We solve this problem with on-demand genetic testing by CHIPS (CEL nuclease mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining) technology, which is the ultimately conventional and economical mutation screening system. In this article, we show eight patients with MCA syndromes who were recently treated at our hospital, and demonstrate that CHIPS successfully offers efficient and inexpensive genetic testing and facilitates clinical genetic service in our local region.

Classification of Uniparental Isodisomy Patterns That Cause Autosomal Recessive Disorders: Proposed Mechanisms of Different Proportions and Parental Origin in Each Pattern

“…The gene mutations were screened by CHIPS (CEL nuclease mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining) technology [Niida et al, 2012a[Niida et al, , 2015 and confirmed by direct sequencing with an ABI 3130xl Genetic Analyser and BigDye version 3.1 Cycle Sequencing Kit (Thermo Fisher Scientific). For patient 3, the SNRPN methylation test was performed according to an established protocol [Kosaki et al, 1997] with some modifications.…”

Development of a practical NF1 genetic testing method through the pilot analysis of five Japanese families with neurofibromatosis type 1

“…To solve this problem, over the past few years we have developed a conventional, highly sensitive and inexpensive mutation screening system for large genes. This new technology, CHIPS (CEL nuclease mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining) [16,17], has already been successfully applied to our daily clinical genetic service [18]. The aim of this study is to establish a practicable and inexpensive NF1 mutation screening system based on CHIPS technology through the pilot analysis of eight patients with NF1 from five independent families, and prepare for a mutational cohort study of Japan and of molecular pathology of NF1 lesions.…”

CHIPS for a Mutation Screening of a Large Sized Gene: An example of NF1 Analysis

“…Actually 100% sensitivity of mutation detection has been accomplished using only commercially available reagents and basic apparatus [4,5]. At the same time, CHIPS offers inexpensive easy mutation screening by cutting out the cost and effort of unnecessary sequencing [6]. Here we demonstrate an example of mutation screening of a patient with NF1.…”