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Lakhssassi K.AuthorLahoz, BelénAuthorPilar Iguacel, LauraAuthorFolch, JoseAuthorAlabart J.l.AuthorHugo Calvo, JorgeCorresponding Author

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January 24, 2021
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The LEPR Gene Is Associated with Reproductive Seasonality Traits in Rasa Aragonesa Sheep

Publicated to: Animals. 10 (12): 1-15 - 2020-12-01 10(12), DOI: 10.3390/ani10122448

Authors:

Lakhssassi, K; Serrano, M; Lahoz, B; Sarto, MP; Iguácel, LP; Folch, J; Alabart, JL; Calvo, JH
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Affiliations

ARAID, Zaragoza 50018, Spain - Author
Dept Mejora Genet Anim INIA, Madrid 28040, Spain - Author
Grupo de investigación INPASS: Investigación en Producción Agroganadera Sostenible y Saludable. Centro de Investigación y Tecnología Agroalimentaria de Aragón - Author
Grupo de investigación Sistemas AgroGanaderos Alimentarios Sostenibles (SAGAS). Centro de Investigación y Tecnología Agroalimentaria de Aragón - Author
Instituto Agroalimentario de Aragón (IA2). Centro de Investigación y Tecnología Agroalimentaria de Aragón - Author
Zaragoza Univ, Ctr Invest & Tecnol Agroalimentaria Aragon, Inst Agroalimentario Aragon IA2, CITA, Zaragoza 50059, Spain - Author
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Abstract

Simple Summary Seasonality of reproduction is one of the limiting factor of sheep production, with the leptin receptor (LEPR) gene associated with some reproductive traits in different species. Thereby, we searched for polymorphisms in the ovine LEPR gene and associated them with three reproductive seasonality traits: the total days of anoestrous (TDA) and the progesterone cycling months (P4CM), both based on blood progesterone level and related to seasonal ovarian function; and the oestrous cycling months (OCM) as an indicator of oestrous behaviour. Two non-synonymous and non-linked single nucleotide polymorphisms (SNPs) in the LEPR gene were involved in the OCM trait (rs403578195 and rs405459906). These findings show for the first time the involvement of LEPR gene in seasonality reproduction in sheep and will help to improve genetic selection programs by implementing the genotyping of reproducers, which might increase the productivity of meat sheep. The aim of this study was to characterize and identify causative polymorphisms in the leptin receptor (LEPR) gene responsible for the seasonal variation of reproductive traits in sheep. Three reproductive seasonality traits were studied: the total days of anoestrous (TDA), the progesterone cycling months (P4CM) and the oestrous cycling months (OCM). In total, 18 SNPs were detected in 33 ewes with extreme values for TDA and OCM. Six SNPs were non-synonymous substitutions and two of them were predicted in silico as deleterious: rs596133197 and rs403578195. These polymorphisms were then validated in 239 ewes. The SNP rs403578195, located in exon 8 and leading to a change of alanine to glycine (Ala284Gly) in the extracellular domain of the protein, was associated with the OCM trait, being the G allele associated with a decrease of 12 percent of the OCM trait. Haplotype analyses also suggested the involvement of other non-synonymous SNP located in exon 20 (rs405459906). This SNP also produces an amino acid change (Lys1069Glu) in the intracellular domain of the protein and segregates independently of rs403578195. These results confirm for the first time the role of the LEPR gene in sheep reproductive seasonality.
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Keywords

haplotypeleptin receptorrasa aragonesasnp1a mtnr1a geneAllele specific polymerase chain reactionAmino acid substitutionAnimal experimentArticleBody constitutionComputer modelDna flanking regionEstrus cycleExpressionGeneGene frequencyGene linkage disequilibriumGenetic selectionGenomic dnaGenotypeHaplotypeLepr geneLeptin receptorLeptin-receptor geneLiveweight gainMelatoninMessenger-rnaNonhumanOvary functionPolymerase chain reactionPolymorphismProgesteroneRasa aragonesaRasa aragonesa sheepReproducción animalReproductionReproductive seasonalitySanger sequencingSarda ewesSeasonal variationSecretionSequence alignmentSingle nucleotide polymorphismSnp

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Animals due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 19/146, thus managing to position itself as a Q1 (Primer Cuartil), in the category Veterinary Sciences.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-03-24:

  • Google Scholar: 9
  • WoS: 11
  • Scopus: 10
  • Europe PMC: 5
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-03-24:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 18 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/10261/344455
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Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Lakhssassi, Kenza) and Last Author (Calvo Lacosta, Jorge Hugo).

the author responsible for correspondence tasks has been Calvo Lacosta, Jorge Hugo.

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Project objectives

El estudio persigue los siguientes objetivos: caracterizar y identificar polimorfismos causales en el gen receptor de leptina (LEPR) relacionados con la variación estacional de rasgos reproductivos en ovejas; analizar tres rasgos de estacionalidad reproductiva: días totales de anestro (TDA), meses de ciclo de progesterona (P4CM) y meses de ciclo estral (OCM); detectar y validar polimorfismos de nucleótido simple (SNPs) en ovejas con valores extremos para TDA y OCM; evaluar la asociación de SNPs no sinónimos, especialmente rs403578195 y rs405459906, con los rasgos reproductivos; y determinar el impacto funcional de estos SNPs en la proteína LEPR para comprender su papel en la estacionalidad reproductiva ovina.
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Most relevant results

El estudio identificó polimorfismos en el gen receptor de leptina (LEPR) asociados con la estacionalidad reproductiva en ovejas Rasa Aragonesa. Se detectaron 18 SNPs en 33 ovejas con valores extremos para días totales de anestro (TDA) y meses de ciclo estral (OCM). Dos SNPs no sinónimos, rs403578195 y rs405459906, se relacionaron con el rasgo OCM. El SNP rs403578195, ubicado en el exón 8 y que provoca un cambio Ala284Gly, se asoció con una reducción del 12% en OCM. El SNP rs405459906, en el exón 20, también mostró implicación independiente. Estos hallazgos confirman por primera vez la influencia del gen LEPR en la estacionalidad reproductiva ovina.
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Awards linked to the item

This study was partially financed by the Ministry of Science, Innovation and Universities of Spain research project INIA-RTA2015-00090, the Research Group Funds of the Aragon Government (Grupo SAGAS Ref. A14_17R) and is co-financed by FEDER. K. Lakhssassi is supported by a doctoral grant from the Ministry of Science, Innovation and Universities of Spain (BES-2017-080154).
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