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pCADD: SNV prioritisation in Sus scrofa.

Christian Groß1,2, Martijn Derks3, Hendrik-Jan Megens3

  • 1Delft Bioinformatics Lab, University of Technology Delft, 2600GA, Delft, The Netherlands. c.gross@tudelft.nl.

Genetics, Selection, Evolution : GSE
|February 9, 2020
PubMed
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We developed pCADD, a new tool to prioritize genetic variants in pigs. This method helps identify important genetic changes for animal breeding by scoring single nucleotide variants (SNVs) based on their potential impact.

Area of Science:

  • Genomics
  • Animal Breeding
  • Bioinformatics

Background:

  • Identifying causative genetic variants is crucial for animal breeding and has high economic value.
  • Prioritizing candidate variants is challenging due to experimental limitations, especially for non-amino acid substituting variants.
  • The Combined Annotation Dependent Depletion (CADD) method, successful in human genomes, provides a theoretical basis for similar approaches in other species.

Purpose of the Study:

  • To develop and present pCADD, a model for scoring single nucleotide variants (SNVs) in pig genomes.
  • To evaluate pCADD's ability to distinguish between functional and non-functional genomic elements.
  • To assess pCADD's utility in prioritizing functionally relevant SNVs in pigs.

Main Methods:

  • pCADD model development for scoring SNVs in pig genomes.

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  • Evaluation using transcripts from miRNAs, introns, and tissue-specific genes.
  • Assessment of coding and non-coding SNVs causal for phenotypic changes.
  • Analysis of pCADD's scoring of codon positions based on redundancy.

    • Main Results:

    • pCADD scores effectively discriminate between functional and non-functional genomic sequences.
    • The model prioritizes functional SNVs and accurately scores codon positions based on their redundancy.
    • pCADD identifies regions of biological relevance and distinguishes them by their rate of adaptation.

    Conclusions:

    • pCADD effectively prioritizes SNVs in the pig genome based on their potential deleteriousness and biological significance.
    • A comprehensive set of pCADD scores for all possible SNVs across the pig genome (Sscrofa11.1) has been generated.
    • This provides a valuable toolbox for prioritizing variants and identifying novel sites of biological interest relevant to animal breeding.