Modular Probes for Enriching and Detecting Complex Nucleic Acid Sequences

Overview

Journal Nat Chem

Specialty Chemistry

Date 2017 Nov 24

PMID 29168489

Citations 9

Authors

Juexiao Sherry Wang

Yan Helen Yan

David Yu Zhang

Affiliations

Soon will be listed here.

Abstract

Complex DNA sequences are difficult to detect and profile, but are important contributors to human health and disease. Existing hybridization probes lack the capability to selectively bind and enrich hypervariable, long or repetitive sequences. Here, we present a generalized strategy for constructing modular hybridization probes (M-Probes) that overcomes these challenges. We demonstrate that M-Probes can tolerate sequence variations of up to 7 nt at prescribed positions while maintaining single nucleotide sensitivity at other positions. M-Probes are also shown to be capable of sequence-selectively binding a continuous DNA sequence of more than 500 nt. Furthermore, we show that M-Probes can detect genes with triplet repeats exceeding a programmed threshold. As a demonstration of this technology, we have developed a hybrid capture method to determine the exact triplet repeat expansion number in the Huntington's gene of genomic DNA using quantitative PCR.

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