Fine mapping of genomic regions associated with female fertility in Nellore beef cattle based on sequence variants from segregating sires

作     者：Gerson A.Oliveira Júnior Daniel J.A.Santos Aline S.M.Cesar Solomon A.Boison Ricardo V.Ventura Bruno C.Perez JoséF.Garcia JoséBento S.Ferraz Dorian J.Garrick Gerson A.Oliveira Júnior;Daniel J.A.Santos;Aline S.M.Cesar;Solomon A.Boison;Ricardo V.Ventura;Bruno C.Perez;José F.Garcia;José Bento S.Ferraz;Dorian J.Garrick

作者机构：Department of Veterinary MedicineUniversity of São Paulo(USP)Faculty of Animal Science and Food EngineerPirassunungaSPBrazil Department of Animal BioscienceCenter for Genetic Improvement of LivestockUniversity of GuelphGuelphONCanada Department of Animal and Avian SciencesUniversity of MarylandCollege ParkMarylandUSA Department of Animal ScienceUniversity of São Paulo(USP)PiracicabaSPBrazil Department of Sustainable Agricultural SystemsUniversity of Natural Resources and Life SciencesViennaAustria Department of Animal Nutrition and ProductionSchool of Veterinary Medicine and Animal ScienceUniversity of São Paulo(USP)PirassunungaBrazil Department of SupportProduction and Animal HealthSchool of Veterinary MedicineSão Paulo State University(Unesp)AraçatubaSPBrazil School of AgricultureMassey UniversityRuakura Ag CentreHamiltonNew Zealand 

出 版 物：《Journal of Animal Science and Biotechnology》 (畜牧与生物技术杂志（英文版）)

年 卷 期：2020年第11卷第2期

页      面：303-315页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 0832[工学-食品科学与工程（可授工学、农学学位）] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 0905[农学-畜牧学] 09[农学] 0906[农学-兽医学] 0703[理学-化学] 0836[工学-生物工程] 

基　　金：supported by the“Fundação de Amparoà Pesquisa do Estado de São Paulo”(FAPESP) under project numbers 2012/50533-2 2013/12097-9 2014/07566-2 2015/12396-1. 

主　　题：Antral follicles Causal variants Haplotype Heifer pregnancy WGS 

摘      要：Background:Impaired fertility in cattle limits the efficiency of livestock production systems.Unraveling the genetic architecture of fertility traits would facilitate their improvement by selection.In this study,we characterized SNP chip haplotypes at QTL blocks then used whole-genome sequencing to fine map genomic regions associated with reproduction in a population of Nellore(Bos indicus)heifers.Methods:The dataset comprised of 1337 heifers genotyped using a GeneSeek®Genomic Profiler panel(74677 SNPs),representing the daughters from 78 sires.After performing marker quality control,64800 SNPs were retained.Haplotypes carried by each sire at six previously identified QTL on BTAs 5,14 and 18 for heifer pregnancy and BTAs 8,11 and 22 for antral follicle count were constructed using findhap software.The significance of the contrasts between the effects of every two paternally-inherited haplotype alleles were used to identify sires that were heterozygous at each QTL.Whole-genome sequencing data localized to the haplotypes from six sires and 20 other ancestors were used to identify sequence variants that were concordant with the haplotype contrasts.Enrichment analyses were applied to these variants using KEGG and MeSH libraries.Results:A total of six(BTA 5),six(BTA 14)and five(BTA 18)sires were heterozygous for heifer pregnancy QTL whereas six(BTA 8),fourteen(BTA 11),and five(BTA 22)sires were heterozygous for number of antral follicles’QTL.Due to inadequate representation of many haplotype alleles in the sequenced animals,fine mapping analysis could only be reliably performed for the QTL on BTA 5 and 14,which had 641 and 3733 concordant candidate sequence variants,respectively.The KEGG“Circadian rhythmand“Neurotrophin signaling pathwaywere significantly associated with the genes in the QTL on BTA 5 whereas 32 MeSH terms were associated with the QTL on BTA 14.Among the concordant sequence variants,0.2%and 0.3%were classified as missense variants for BTAs 5 and 14,respectively,highlighting the genes MTERF2,RTMB,ENSBTAG00000037306(miRNA),ENSBTAG00000040351,PRKDC,and RGS20.The potential causal mutations found in the present study were associated with biological processes such as oocyte maturation,embryo development,placenta development and response to reproductive hormones.Conclusions:The identification of heterozygous sires by positionally phasing SNP chip data and contrasting haplotype effects for previously detected QTL can be used for fine mapping to identify potential causal mutations and candidate genes.Genomic variants on genes MTERF2,RTBC,miRNA ENSBTAG00000037306,ENSBTAG00000040351,PRKDC,and RGS20,which are known to have influence on reproductive biological processes,were detected.