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Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality

SIMPLE SUMMARY: To elucidate the genetic basis of reproductive seasonality in Rasa Aragonesa sheep breed, we performed a genome-wide association study (GWAS) in order to detect single nucleotide polymorphisms (SNPs) or regions associated with traits related to ovarian function and behavioural signs...

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Autores principales: Lakhssassi, Kenza, Lahoz, Belén, Sarto, Pilar, Iguácel, Laura Pilar, Folch, José, Alabart, José Luis, Serrano, Malena, Calvo, Jorge Hugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074133/
https://www.ncbi.nlm.nih.gov/pubmed/33921837
http://dx.doi.org/10.3390/ani11041171
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author Lakhssassi, Kenza
Lahoz, Belén
Sarto, Pilar
Iguácel, Laura Pilar
Folch, José
Alabart, José Luis
Serrano, Malena
Calvo, Jorge Hugo
author_facet Lakhssassi, Kenza
Lahoz, Belén
Sarto, Pilar
Iguácel, Laura Pilar
Folch, José
Alabart, José Luis
Serrano, Malena
Calvo, Jorge Hugo
author_sort Lakhssassi, Kenza
collection PubMed
description SIMPLE SUMMARY: To elucidate the genetic basis of reproductive seasonality in Rasa Aragonesa sheep breed, we performed a genome-wide association study (GWAS) in order to detect single nucleotide polymorphisms (SNPs) or regions associated with traits related to ovarian function and behavioural signs of estrous. The GWAS included 205 ewes with genotypes for 583882 SNPs. Only one SNP overcame the genome-wide significance level. Nine potential SNPs overcame the chromosome-wise significance level (FDR 10%). Gene annotation demonstrated that CD226 molecule (CD226) and neuropeptide Y (NPY) genes that could be involved in reproductive seasonality were close to the significant SNPs. To validate the results, we sequenced the entire coding region of the NPY gene and four exons of the CD226 gene to search for polymorphisms that could be involved in the phenotypes studied. Two synonymous and two nonsynonymous SNPs in the NPY and CD226 genes, respectively, were genotyped in the whole population. We demonstrated that the AA genotype of the SNP rs404360094 located in exon 3 of the CD226 gene was associated with higher and lower total days of anoestrus and oestrous cycling months, respectively. Therefore, this SNP could be utilized as a genetic marker for assisted selection marker to reduce seasonality. ABSTRACT: A genome-wide association study (GWAS) was used to identify genomic regions influencing seasonality reproduction traits in Rasa Aragonesa sheep. Three traits associated with either ovarian function based on blood progesterone levels (total days of anoestrus and progesterone cycling months) or behavioral signs of oestrous (oestrous cycling months) were studied. The GWAS included 205 ewes genotyped using the 50k and 680k Illumina Ovine Beadchips. Only one SNP associated with the progesterone cycling months overcame the genome-wide significance level (rs404991855). Nine SNPs exhibited significant associations at the chromosome level, being the SNPs rs404991855 and rs418191944, that are located in the CD226 molecule (CD226) gene, associated with the three traits. This gene is related to reproductive diseases. Two other SNPs were located close to the neuropeptide Y (NPY) gene, which is involved in circadian rhythms. To validate the GWAS, partial characterization of both genes by Sanger sequencing, and genotyping of two synonymous and two nonsynonymous SNPs in the NPY and CD226 genes, respectively, were performed. SNP association analysis showed that only SNP rs404360094 in the exon 3 of the CD226 gene, which produces an amino acid substitution from asparagine (uncharged polar) to aspartic acid (acidic), was associated with the three seasonality traits. Our results suggest that the CD226 gene may be involved in the reproductive seasonality in Rasa Aragonesa.
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spelling pubmed-80741332021-04-27 Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality Lakhssassi, Kenza Lahoz, Belén Sarto, Pilar Iguácel, Laura Pilar Folch, José Alabart, José Luis Serrano, Malena Calvo, Jorge Hugo Animals (Basel) Article SIMPLE SUMMARY: To elucidate the genetic basis of reproductive seasonality in Rasa Aragonesa sheep breed, we performed a genome-wide association study (GWAS) in order to detect single nucleotide polymorphisms (SNPs) or regions associated with traits related to ovarian function and behavioural signs of estrous. The GWAS included 205 ewes with genotypes for 583882 SNPs. Only one SNP overcame the genome-wide significance level. Nine potential SNPs overcame the chromosome-wise significance level (FDR 10%). Gene annotation demonstrated that CD226 molecule (CD226) and neuropeptide Y (NPY) genes that could be involved in reproductive seasonality were close to the significant SNPs. To validate the results, we sequenced the entire coding region of the NPY gene and four exons of the CD226 gene to search for polymorphisms that could be involved in the phenotypes studied. Two synonymous and two nonsynonymous SNPs in the NPY and CD226 genes, respectively, were genotyped in the whole population. We demonstrated that the AA genotype of the SNP rs404360094 located in exon 3 of the CD226 gene was associated with higher and lower total days of anoestrus and oestrous cycling months, respectively. Therefore, this SNP could be utilized as a genetic marker for assisted selection marker to reduce seasonality. ABSTRACT: A genome-wide association study (GWAS) was used to identify genomic regions influencing seasonality reproduction traits in Rasa Aragonesa sheep. Three traits associated with either ovarian function based on blood progesterone levels (total days of anoestrus and progesterone cycling months) or behavioral signs of oestrous (oestrous cycling months) were studied. The GWAS included 205 ewes genotyped using the 50k and 680k Illumina Ovine Beadchips. Only one SNP associated with the progesterone cycling months overcame the genome-wide significance level (rs404991855). Nine SNPs exhibited significant associations at the chromosome level, being the SNPs rs404991855 and rs418191944, that are located in the CD226 molecule (CD226) gene, associated with the three traits. This gene is related to reproductive diseases. Two other SNPs were located close to the neuropeptide Y (NPY) gene, which is involved in circadian rhythms. To validate the GWAS, partial characterization of both genes by Sanger sequencing, and genotyping of two synonymous and two nonsynonymous SNPs in the NPY and CD226 genes, respectively, were performed. SNP association analysis showed that only SNP rs404360094 in the exon 3 of the CD226 gene, which produces an amino acid substitution from asparagine (uncharged polar) to aspartic acid (acidic), was associated with the three seasonality traits. Our results suggest that the CD226 gene may be involved in the reproductive seasonality in Rasa Aragonesa. MDPI 2021-04-19 /pmc/articles/PMC8074133/ /pubmed/33921837 http://dx.doi.org/10.3390/ani11041171 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lakhssassi, Kenza
Lahoz, Belén
Sarto, Pilar
Iguácel, Laura Pilar
Folch, José
Alabart, José Luis
Serrano, Malena
Calvo, Jorge Hugo
Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality
title Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality
title_full Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality
title_fullStr Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality
title_full_unstemmed Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality
title_short Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality
title_sort genome-wide association study demonstrates the role played by the cd226 gene in rasa aragonesa sheep reproductive seasonality
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074133/
https://www.ncbi.nlm.nih.gov/pubmed/33921837
http://dx.doi.org/10.3390/ani11041171
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