Abstract
BackgroundTarget capture sequencing is an efficient approach to directly identify the causative mutations of genetic disorders. To apply this strategy to laboratory rats exhibiting various phenotypes, we developed a novel target capture probe set, TargetEC (target capture for exons and conserved non-coding sequences), which can identify mutations not only in exonic regions but also in conserved non-coding sequences and thus can detect regulatory mutations.ResultsTargetEC covers 1,078,129 regions spanning 146.8 Mb of the genome. We applied TargetEC to four inbred rat strains (WTC/Kyo, WTC-swh/Kyo, PVG/Seac, and KFRS4/Kyo) maintained by the National BioResource Project for the Rat in Japan, and successfully identified mutations associated with these phenotypes, including one mutation detected in a conserved non-coding sequence.ConclusionsThe method developed in this study can be used to efficiently identify regulatory mutations, which cannot be detected using conventional exome sequencing, and will help to deepen our understanding of the relationships between regulatory mutations and associated phenotypes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2975-9) contains supplementary material, which is available to authorized users.
Highlights
Target capture sequencing is an efficient approach to directly identify the causative mutations of genetic disorders
Since the use of this method to select an entire set of human exons for sequencing using probe hybridization [1] and its first application for the identification of a gene involved in a genetic disease were reported [2], Whole exome sequencing (WES) has been successfully applied to the identification of responsible genes and their causative mutations in many diseases
A certain fraction of conserved non-coding sequence (CNS) might correspond to regulatory elements for gene expression, which are not well annotated even in the human and mouse genomes
Summary
Target capture sequencing is an efficient approach to directly identify the causative mutations of genetic disorders. To apply this strategy to laboratory rats exhibiting various phenotypes, we developed a novel target capture probe set, TargetEC (target capture for exons and conserved non-coding sequences), which can identify mutations in exonic regions and in conserved non-coding sequences and can detect regulatory mutations. Since the use of this method to select an entire set of human exons for sequencing using probe hybridization [1] and its first application for the identification of a gene involved in a genetic disease were reported [2], WES has been successfully applied to the identification of responsible genes and their causative mutations in many diseases (for review, see [3]). These species include dogs [7, 8], pigs [9], cows/bison [10], chipmunks [11], and non-human primates [12]
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