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

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 rhythm”and“Neurotrophin signaling pathway”were 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.

An atlas of expression quantitative trait loci of microRNAs in longissimus muscle of eight-way crossbred pigs

MicroRNAs(miRNAs)are key regulators of myocyte development and traits,yet insight into the genetic basis of variation in miRNA expression is still limited.Here,we present a systematic analysis of expression quantitative trait loci(eQTL)for miRNA profiling in longissimus muscle of pigs from an eight-breed crossed heterogeneous population.By integrating the whole-genome sequencing and miRNAomics data,we map 54 cis-and 292 trans-e QTLs at high resolution that are associated with the expression of 54 and 92miRNAs,respectively.Twenty-three trans-acting loci are identified to affect the expression of nine myomi Rs(known muscle-specific miRNAs).MiRNAs in mammalian conserved miRNA clusters are found to be subjected to regulation by shared cis-e QTLs,while the expression of mature miRNA-5p/-3p counterparts is more likely to be regulated by different cis-e QTLs.Fine mapping and bioinformatics analyses pinpoint the peak cis-e SNP of mi R-4331-5p,rs344650810,which is located in its seed region,as a causal variant for the changes in expression and function of this miRNA.Additionally,rs344650810 is significantly(P<0.01)correlated with the density and percentage of type I muscle fibers.Altogether,this study provides a comprehensive atlas of miRNA-e QTLs in porcine skeletal muscle and new insights into regulatory mechanisms of miRNA expression.