Hodgens Charles, Nimchuk Zachary L, Kieber Joseph J
Curriculum in Genetics and Molecular Biology, UNC Chapel Hill, Chapel Hill, USA.
Department of Biology, UNC Chapel Hill, Chapel Hill, USA.
Bio Protoc. 2019 Sep 20;9(18):e3374. doi: 10.21769/BioProtoc.3374.
Cleaved amplified polymorphic sequences (CAPS) assays are useful tools for detecting small mutations such as single nucleotide polymorphisms (SNPs) or insertion/deletions (indels) present in an amplified DNA fragment. A mutation that disrupts or creates a restriction site will prevent cleavage by a restriction enzyme, allowing discrimination of wild-type and mutant alleles. In cases where no convenient restriction site is present, a derived Cleaved Amplified Polymorphic Sequence (dCAPS) assay can be used, where mismatches in the primer are used to create a diagnostic restriction site. No special design constraints are present for a CAPS assay, but cases where CAPS assays can be used are infrequent. A dCAPS assay can be burdensome to design by hand, but it is more broadly applicable. This protocol will describe the use of the indCAPS tool for the design of CAPS and dCAPS primers. The indCAPS tool was designed to be compatible with indel alleles, which prior tools struggled with but have increased importance since the rise of CRISPR/Cas9 mutagenesis methods.
酶切扩增多态性序列(CAPS)分析是检测扩增DNA片段中存在的小突变(如单核苷酸多态性(SNP)或插入/缺失(indel))的有用工具。破坏或产生限制酶切位点的突变将阻止限制酶的切割,从而能够区分野生型和突变型等位基因。在不存在合适限制酶切位点的情况下,可以使用衍生的酶切扩增多态性序列(dCAPS)分析,其中引物中的错配用于创建诊断性限制酶切位点。CAPS分析不存在特殊的设计限制,但可使用CAPS分析的情况并不常见。手工设计dCAPS分析可能很繁琐,但它具有更广泛的适用性。本方案将描述使用indCAPS工具设计CAPS和dCAPS引物。indCAPS工具设计为与indel等位基因兼容,这是之前的工具难以处理的,但自CRISPR/Cas9诱变方法兴起以来变得越来越重要。