Long-read sequencing reveals the splicing profile of the calcium channel gene CACNA1C in human brain

RNA splicing is a key mechanism linking genetic variation and complex diseases, including schizophrenia. Splicing profiles are particularly diverse in the brain, but it is difficult to accurately identify and quantify full-length isoforms using standard approaches. CACNA1C is a large gene that shows robust genetic associations with several psychiatric disorders and encodes multiple, functionally-distinct voltage-gated calcium channels via alternative splicing. We combined long-range PCR with nanopore sequencing to characterise the full-length coding sequences of the CACNA1C gene in human brain. We show that its splice isoform profile varies between brain regions and is substantially more complex than currently appreciated: we identified 38 novel exons and 83 high confidence novel isoforms, many of which are predicted to alter protein function. Our findings demonstrate the capability of long-read amplicon sequencing to effectively characterise human splice isoform diversity, while the accurate characterisation of CACNA1C isoforms will facilitate the identification of disease-linked isoforms.

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Citation Report https://scite.ai/reports/10.1101/260562
DOI 10.1101/260562
Date Last Updated 2019-05-20T15:24:33.044376
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Open Access Status bronze
PDF URL https://www.biorxiv.org/content/biorxiv/early/2018/02/05/260562.full.pdf
Publisher URL https://doi.org/10.1101/260562