Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs
Summary 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...
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creator | Torrecilha, R. B. P. Milanesi, M. Gallana, M. Falbo, A.‐K. Reichler, I. M. Hug, P. Jagannathan, V. Trigo, B. B. Paulan, S. C. Bruno, D. B. Garcia, S. D. Scaramele, N. F. Lopes, F. L. Dolf, G. Leeb, T. Sölkner, J. Garcia, J. F. Pieńkowska‐Schelling, A. Schelling, C. Utsunomiya, Y. T. |
description | Summary
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. |
doi_str_mv | 10.1111/age.12882 |
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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.</description><identifier>ISSN: 0268-9146</identifier><identifier>EISSN: 1365-2052</identifier><identifier>DOI: 10.1111/age.12882</identifier><identifier>PMID: 31802524</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Amino Acid Sequence ; Amino acid substitution ; Amino acids ; Animals ; Breeding ; Canidae ; Canis lupus familiaris ; Deletion ; Dogs ; Dogs - genetics ; Female ; Gametocytes ; Genetic Association Studies - veterinary ; Genotype ; Genotypes ; Growth differentiation factor 9 ; Growth Differentiation Factor 9 - genetics ; Heritability ; Litter size ; Litter Size - genetics ; Male ; Markers ; Maturation ; Meiosis ; Mountains ; multiple ovulation ; Mutation, Missense ; Nucleotides ; number of offspring ; Oocytes ; Oviduct ; Pedigree ; Phenotype ; Phenotypes ; Proline ; Prophase ; Serine ; single nucleotide polymorphism ; single‐step genomic best linear unbiased prediction ; Substitutes ; Variance analysis ; Vertebrates</subject><ispartof>Animal genetics, 2020-02, Vol.51 (1), p.78-86</ispartof><rights>2019 Stichting International Foundation for Animal Genetics</rights><rights>2019 Stichting International Foundation for Animal Genetics.</rights><rights>Copyright © 2020 Stichting International Foundation for Animal Genetics</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-a18ef1ccb2e90a2fead557a98dda403f41951f3e4f7b257b65fd5fcabd9a0eee3</citedby><cites>FETCH-LOGICAL-c3532-a18ef1ccb2e90a2fead557a98dda403f41951f3e4f7b257b65fd5fcabd9a0eee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fage.12882$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fage.12882$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31802524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Torrecilha, R. B. P.</creatorcontrib><creatorcontrib>Milanesi, M.</creatorcontrib><creatorcontrib>Gallana, M.</creatorcontrib><creatorcontrib>Falbo, A.‐K.</creatorcontrib><creatorcontrib>Reichler, I. M.</creatorcontrib><creatorcontrib>Hug, P.</creatorcontrib><creatorcontrib>Jagannathan, V.</creatorcontrib><creatorcontrib>Trigo, B. B.</creatorcontrib><creatorcontrib>Paulan, S. C.</creatorcontrib><creatorcontrib>Bruno, D. B.</creatorcontrib><creatorcontrib>Garcia, S. D.</creatorcontrib><creatorcontrib>Scaramele, N. F.</creatorcontrib><creatorcontrib>Lopes, F. L.</creatorcontrib><creatorcontrib>Dolf, G.</creatorcontrib><creatorcontrib>Leeb, T.</creatorcontrib><creatorcontrib>Sölkner, J.</creatorcontrib><creatorcontrib>Garcia, J. F.</creatorcontrib><creatorcontrib>Pieńkowska‐Schelling, A.</creatorcontrib><creatorcontrib>Schelling, C.</creatorcontrib><creatorcontrib>Utsunomiya, Y. T.</creatorcontrib><title>Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs</title><title>Animal genetics</title><addtitle>Anim Genet</addtitle><description>Summary
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.</description><subject>Amino Acid Sequence</subject><subject>Amino acid substitution</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Breeding</subject><subject>Canidae</subject><subject>Canis lupus familiaris</subject><subject>Deletion</subject><subject>Dogs</subject><subject>Dogs - genetics</subject><subject>Female</subject><subject>Gametocytes</subject><subject>Genetic Association Studies - veterinary</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Growth differentiation factor 9</subject><subject>Growth Differentiation Factor 9 - genetics</subject><subject>Heritability</subject><subject>Litter size</subject><subject>Litter Size - genetics</subject><subject>Male</subject><subject>Markers</subject><subject>Maturation</subject><subject>Meiosis</subject><subject>Mountains</subject><subject>multiple ovulation</subject><subject>Mutation, Missense</subject><subject>Nucleotides</subject><subject>number of offspring</subject><subject>Oocytes</subject><subject>Oviduct</subject><subject>Pedigree</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Proline</subject><subject>Prophase</subject><subject>Serine</subject><subject>single nucleotide polymorphism</subject><subject>single‐step genomic best linear unbiased prediction</subject><subject>Substitutes</subject><subject>Variance analysis</subject><subject>Vertebrates</subject><issn>0268-9146</issn><issn>1365-2052</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E9PwjAYBvDGaATRg1_ALPGih0H7dt2fI0FAE40X9bp021soGSuumwQ_vcWhBxN7afL2lyd9H0IuGR0yd0ZygUMGcQxHpM94KHygAo5Jn0IY-wkLwh45s3ZFKY1ZxE5Jj7OYgoCgT97G1ppcy0abyjPKW2trsbLofchay6qxnq68-d0s8ba6WXqlbhqsPas_cf8wrZoSszZfutmTaatGumFhFvacnChZWrw43APyOpu-TO79x-f5w2T86OdccPAli1GxPM8AEypBoSyEiGQSF4UMKFcBSwRTHAMVZSCiLBSqECqXWZFIioh8QG663E1t3lu0TeoWyLEsZYWmtSlwABZAEoCj13_oyrR15X7nFA_CkEJCnbrtVF4ba2tU6abWa1nvUkbTfdmpKzv9LtvZq0Nim62x-JU_7Tow6sBWl7j7Pykdz6dd5Bf3ioip</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Torrecilha, R. B. P.</creator><creator>Milanesi, M.</creator><creator>Gallana, M.</creator><creator>Falbo, A.‐K.</creator><creator>Reichler, I. M.</creator><creator>Hug, P.</creator><creator>Jagannathan, V.</creator><creator>Trigo, B. B.</creator><creator>Paulan, S. C.</creator><creator>Bruno, D. B.</creator><creator>Garcia, S. D.</creator><creator>Scaramele, N. F.</creator><creator>Lopes, F. L.</creator><creator>Dolf, G.</creator><creator>Leeb, T.</creator><creator>Sölkner, J.</creator><creator>Garcia, J. F.</creator><creator>Pieńkowska‐Schelling, A.</creator><creator>Schelling, C.</creator><creator>Utsunomiya, Y. T.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>202002</creationdate><title>Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs</title><author>Torrecilha, R. B. P. ; Milanesi, M. ; Gallana, M. ; Falbo, A.‐K. ; Reichler, I. M. ; Hug, P. ; Jagannathan, V. ; Trigo, B. B. ; Paulan, S. C. ; Bruno, D. B. ; Garcia, S. D. ; Scaramele, N. F. ; Lopes, F. L. ; Dolf, G. ; Leeb, T. ; Sölkner, J. ; Garcia, J. F. ; Pieńkowska‐Schelling, A. ; Schelling, C. ; Utsunomiya, Y. 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B. P.</creatorcontrib><creatorcontrib>Milanesi, M.</creatorcontrib><creatorcontrib>Gallana, M.</creatorcontrib><creatorcontrib>Falbo, A.‐K.</creatorcontrib><creatorcontrib>Reichler, I. M.</creatorcontrib><creatorcontrib>Hug, P.</creatorcontrib><creatorcontrib>Jagannathan, V.</creatorcontrib><creatorcontrib>Trigo, B. B.</creatorcontrib><creatorcontrib>Paulan, S. C.</creatorcontrib><creatorcontrib>Bruno, D. B.</creatorcontrib><creatorcontrib>Garcia, S. D.</creatorcontrib><creatorcontrib>Scaramele, N. F.</creatorcontrib><creatorcontrib>Lopes, F. L.</creatorcontrib><creatorcontrib>Dolf, G.</creatorcontrib><creatorcontrib>Leeb, T.</creatorcontrib><creatorcontrib>Sölkner, J.</creatorcontrib><creatorcontrib>Garcia, J. F.</creatorcontrib><creatorcontrib>Pieńkowska‐Schelling, A.</creatorcontrib><creatorcontrib>Schelling, C.</creatorcontrib><creatorcontrib>Utsunomiya, Y. T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Animal genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torrecilha, R. B. P.</au><au>Milanesi, M.</au><au>Gallana, M.</au><au>Falbo, A.‐K.</au><au>Reichler, I. M.</au><au>Hug, P.</au><au>Jagannathan, V.</au><au>Trigo, B. B.</au><au>Paulan, S. C.</au><au>Bruno, D. B.</au><au>Garcia, S. D.</au><au>Scaramele, N. F.</au><au>Lopes, F. L.</au><au>Dolf, G.</au><au>Leeb, T.</au><au>Sölkner, J.</au><au>Garcia, J. F.</au><au>Pieńkowska‐Schelling, A.</au><au>Schelling, C.</au><au>Utsunomiya, Y. T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs</atitle><jtitle>Animal genetics</jtitle><addtitle>Anim Genet</addtitle><date>2020-02</date><risdate>2020</risdate><volume>51</volume><issue>1</issue><spage>78</spage><epage>86</epage><pages>78-86</pages><issn>0268-9146</issn><eissn>1365-2052</eissn><abstract>Summary
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.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31802524</pmid><doi>10.1111/age.12882</doi><tpages>9</tpages></addata></record> |
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subjects | Amino Acid Sequence Amino acid substitution Amino acids Animals Breeding Canidae Canis lupus familiaris Deletion Dogs Dogs - genetics Female Gametocytes Genetic Association Studies - veterinary Genotype Genotypes Growth differentiation factor 9 Growth Differentiation Factor 9 - genetics Heritability Litter size Litter Size - genetics Male Markers Maturation Meiosis Mountains multiple ovulation Mutation, Missense Nucleotides number of offspring Oocytes Oviduct Pedigree Phenotype Phenotypes Proline Prophase Serine single nucleotide polymorphism single‐step genomic best linear unbiased prediction Substitutes Variance analysis Vertebrates |
title | Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs |
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