Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs

Autor(es):Mostrar menos -

Torrecilha, R. B. P. ^{[1, 2]} ; Milanesi, M. ^{[1, 3]} ; Gallana, M. ^[4] ; Falbo, A. -K. ^[4] ; Reichler, I. M. ^[5] ; Hug, P. ^[6] ; Jagannathan, V. ^[6] ; Trigo, B. B. ^{[1, 3]} ; Paulan, S. C. ^{[1, 3]} ; Bruno, D. B. ^[7] ; Garcia, S. D. ^[7] ; Scaramele, N. F. ^[3] ; Lopes, F. L. ^[3] ; Dolf, G. ^[6] ; Leeb, T. ^[6] ; Soelkner, J. ^{[3, 8]} ; Garcia, J. F. ^{[1, 3, 2]} ; Pienkowska-Schelling, A. ^{[4, 6]} ; Schelling, C. ^[4] ; Utsunomiya, Y. T. ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] IAEA, Collaborating Ctr Anim Genom & Bioinformat, Clovis Pestana 793, BR-16050680 Aracatuba, SP - Brazil

^[2] Sao Paulo State Univ Unesp, Sch Agr & Vet Sci, Dept Prevent Vet Med & Anim Reprod, Via Acesso Prof Paulo Donato Castellane S-N, BR-14884900 Jaboticabal, SP - Brazil

^[3] Sao Paulo State Univ Unesp, Sch Vet Med, Dept Support Prod & Anim Hlth, Clovis Pestana 793, BR-16050680 Aracatuba, SP - Brazil

^[4] Univ Zurich, Vetsuisse Fac, Clin Reprod Med, Eschikon 27, CH-8315 Lindau - Switzerland

^[5] Univ Zurich, Vetsuisse Fac, Clin Reprod Med, Winterthurerstr 260, CH-8057 Zurich - Switzerland

^[6] Univ Bern, Vetsuisse Fac, Inst Genet, Bremgartenstr 109A, CH-3012 Bern - Switzerland

^[7] Sao Paulo State Univ Unesp, Sch Vet Med, Dept Clin Surg & Anim Reprod, Clovis Pestana 793, BR-16050680 Aracatuba, SP - Brazil

^[8] BOKU Univ Nat Resource & Live Sci, Dept Sustainable Agr Syst, Div Livestook Sci, Gregor Mendel Str 33, A-1180 Vienna - Austria

• Tipo de documento: Artigo Científico
• Fonte: ANIMAL GENETICS; v. 51, n. 1, p. 78-86, FEB 2020.
• Citações Web of Science: 0

Resumo

In the past two decades, average litter size (ALS) in Entlebucher Mountain dogs decreased by approximately 0.8 puppies. We conducted a GWAS for ALS using the single-step methodology to take advantage of 1632 pedigree records, 892 phenotypes and 372 genotypes (173 662 markers) for which only 12% of the dogs had both phenotypes and genotypes available. Our analysis revealed associations towards the growth differentiation factor 9 gene (GDF9), which is known to regulate oocyte maturation. The trait heritability was estimated at 43.1%, from which approximately 15% was accountable by the GDF9 locus alone. Therefore, markers flanking GDF9 explained approximately 6.5% of the variance in ALS. Analysis of WGSs revealed two missense substitutions in GDF9, one of which (g.11:21147009G>A) affected a highly conserved nucleotide in vertebrates. The derived allele A was validated in 111 dogs and shown to be associated with decreased ALS (-0.75 +/- 0.22 puppies per litter). The variant was further predicted to cause a proline to serine substitution. The affected residue was immediately followed by a six-residue deletion that is fixed in the canine species but absent in non-canids. We further confirmed that the deletion is prevalent in the Canidae family by sequencing three species of wild canids. Since canids uniquely ovulate oocytes at the prophase stage of the first meiotic division, requiring maturation in the oviduct, we conjecture that the amino acid substitution and the six-residue deletion of GDF9 may serve as a model for insights into the dynamics of oocyte maturation in canids. (AU)

• Processo FAPESP: 17/08373-1 - Detecção de alelos deletérios através de ausência de homozigose haplotípica em cães
• Beneficiário: Rafaela Beatriz Pintor Torrecilha
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/05787-7 - Combinando tecnologias genômicas (SNP chips e sequenciamento de última geração) para mapear variantes genéticas desvantajosas em bovinos da raça Nelore
• Beneficiário: Marco Milanesi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado