Population Fitness and Genetic Load of Single Nucleotide Polymorphisms Affecting mRNA splicing

TL;DR

This study assesses how single nucleotide polymorphisms that affect mRNA splicing influence human genetic fitness and load, revealing that many high-impact variants are common and supported by expression data.

Contribution

It introduces a quantitative framework to evaluate the fitness and genetic load of SNPs affecting splicing, linking sequence changes to population-level effects.

Findings

High genetic load SNPs are prevalent in the human genome.

Many SNPs with predicted splicing effects are supported by gene expression data.

SNPs with high load (>0.5) are often common in populations.

Abstract

Deleterious genetic variants can be evaluated as quantitative traits using information theory-based sequence analysis of recognition sites. To assess the effect of such variants, fitness and genetic load of SNPs which alter binding site affinity are derived from changes in individual information and allele frequencies. Human SNPs that alter mRNA splicing are partitioned according to their genetic load. SNPs with high genetic loads (>0.5) are common in the genome and, in many instances, predicted effects are supported by gene expression studies.