Watch Out for a Second SNP: Focus on Multi-Nucleotide Variants in Coding Regions and Rescued Stop-Gained
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 varia...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.659287/full |
| _version_ | 1818737852774612992 |
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| author | Fabien Degalez Frédéric Jehl Kévin Muret Maria Bernard Maria Bernard Frédéric Lecerf Laetitia Lagoutte Colette Désert Frédérique Pitel Christophe Klopp Sandrine Lagarrigue |
| author_facet | Fabien Degalez Frédéric Jehl Kévin Muret Maria Bernard Maria Bernard Frédéric Lecerf Laetitia Lagoutte Colette Désert Frédérique Pitel Christophe Klopp Sandrine Lagarrigue |
| author_sort | Fabien Degalez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T00:59:38Z |
| format | Article |
| id | doaj.art-8ec8210e2dd347a5af0491a8072b8ddd |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-18T00:59:38Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-8ec8210e2dd347a5af0491a8072b8ddd2022-12-21T21:26:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-07-011210.3389/fgene.2021.659287659287Watch Out for a Second SNP: Focus on Multi-Nucleotide Variants in Coding Regions and Rescued Stop-GainedFabien Degalez0Frédéric Jehl1Kévin Muret2Maria Bernard3Maria Bernard4Frédéric Lecerf5Laetitia Lagoutte6Colette Désert7Frédérique Pitel8Christophe Klopp9Sandrine Lagarrigue10INRAE, INSTITUT AGRO, PEGASE UMR 1348, Saint-Gilles, FranceINRAE, INSTITUT AGRO, PEGASE UMR 1348, Saint-Gilles, FranceINRAE, INSTITUT AGRO, PEGASE UMR 1348, Saint-Gilles, FranceINRAE, SIGENAE, Genotoul Bioinfo MIAT, Castanet-Tolosan, FranceINRAE, AgroParisTech, Université Paris-Saclay, GABI UMR 1313, Jouy-en-Josas, FranceINRAE, INSTITUT AGRO, PEGASE UMR 1348, Saint-Gilles, FranceINRAE, INSTITUT AGRO, PEGASE UMR 1348, Saint-Gilles, FranceINRAE, INSTITUT AGRO, PEGASE UMR 1348, Saint-Gilles, FranceINRAE, INPT, ENVT, Université de Toulouse, GenPhySE UMR 1388, Castanet-Tolosan, FranceINRAE, SIGENAE, Genotoul Bioinfo MIAT, Castanet-Tolosan, FranceINRAE, INSTITUT AGRO, PEGASE UMR 1348, Saint-Gilles, FranceMost 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.https://www.frontiersin.org/articles/10.3389/fgene.2021.659287/fullMNVSNPvariationrescued stop-gainedSLC27A4FATP4 |
| spellingShingle | Fabien Degalez Frédéric Jehl Kévin Muret Maria Bernard Maria Bernard Frédéric Lecerf Laetitia Lagoutte Colette Désert Frédérique Pitel Christophe Klopp Sandrine Lagarrigue Watch Out for a Second SNP: Focus on Multi-Nucleotide Variants in Coding Regions and Rescued Stop-Gained Frontiers in Genetics MNV SNP variation rescued stop-gained SLC27A4 FATP4 |
| title | Watch Out for a Second SNP: Focus on Multi-Nucleotide Variants in Coding Regions and Rescued Stop-Gained |
| title_full | Watch Out for a Second SNP: Focus on Multi-Nucleotide Variants in Coding Regions and Rescued Stop-Gained |
| title_fullStr | Watch Out for a Second SNP: Focus on Multi-Nucleotide Variants in Coding Regions and Rescued Stop-Gained |
| title_full_unstemmed | Watch Out for a Second SNP: Focus on Multi-Nucleotide Variants in Coding Regions and Rescued Stop-Gained |
| title_short | Watch Out for a Second SNP: Focus on Multi-Nucleotide Variants in Coding Regions and Rescued Stop-Gained |
| title_sort | watch out for a second snp focus on multi nucleotide variants in coding regions and rescued stop gained |
| topic | MNV SNP variation rescued stop-gained SLC27A4 FATP4 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.659287/full |
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