期刊
FRONTIERS IN GENETICS
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2021.659287
关键词
MNV; SNP; variation; rescued stop-gained; FATP4
资金
- European Union's H2020 Program [633531]
- French National Agency of Research (FatInteger project) [ANR-11-SVS7]
- French National Agency of Research (ChickStress project) [ANR-13-ADAP]
- French National Agency of Research (EpiBird ANR project) [PCS-09-GENM-010]
- French institution Institut Agro (AGROCAMPUS OUEST)
- French institution INRAE [Fr-AgENCODE project]
- French institution ELASTICe project
- Brittany region (France)
- INRAE Animal Genetics division
Most single-nucleotide polymorphisms (SNPs) are located in non-coding regions, but the fraction usually studied is in protein-coding regions to predict impacts on proteins. Haplotype-aware variant annotation is valuable in considering multi-nucleotide variants (MNVs) in coding regions for severe functional consequences such as stop-gained variants.
Most single-nucleotide polymorphisms (SNPs) are located in non-coding regions, but the fraction usually studied is harbored in protein-coding regions because potential impacts on proteins are relatively easy to predict by popular tools such as the Variant Effect Predictor. These tools annotate variants independently without considering the potential effect of grouped or haplotypic variations, often called multi-nucleotide variants (MNVs). Here, we used a large RNA-seq dataset to survey MNVs, comprising 382 chicken samples originating from 11 populations analyzed in the companion paper in which 9.5M SNPs- including 3.3M SNPs with reliable genotypes-were detected. We focused our study on in-codon MNVs and evaluate their potential mis-annotation. Using GATK HaplotypeCaller read-based phasing results, we identified 2,965 MNVs observed in at least five individuals located in 1,792 genes. We found 41.1% of them showing a novel impact when compared to the effect of their constituent SNPs analyzed separately. The biggest impact variation flux concerns the originally annotated stop-gained consequences, for which around 95% were rescued; this flux is followed by the missense consequences for which 37% were reannotated with a different amino acid. We then present in more depth the rescued stop-gained MNVs and give an illustration in the SLC27A4 gene. As previously shown in human datasets, our results in chicken demonstrate the value of haplotype-aware variant annotation, and the interest to consider MNVs in the coding region, particularly when searching for severe functional consequence such as stop-gained variants.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据