Whole-genome Resequencing Reveals Key Genes Associated With Milk Production Traits In Guanzhong Dairy Goats

Guanzhong dairy goat is a breed of goat formed through long-term artificial selection and breeding,with characteristics of rough feeding resistance,high milk production and good milk quality,which is one of the excellent dairy goat breeds in China.In recent years,due to less basic research on dairy goat breeding in China,genetic progress has been slow,leading to a decline in milk production performance and large differences in milk yield between individuals,which has seriously restricted the high-quality development of the dairy goat industry.The milk production trait of dairy goats is a quantitative trait regulated by the main effect genes and various micro-effect genes,meanwhile,the milk production trait is a major economic trait,and it is important for the dairy goat breeding industry to select individuals with high milk production in the breeding work.The resequencing of the genomes of different breeds of livestock can reveal candidate genes and genetic variants that affect important economic traits in livestock breeding such as fertility,meat production and milk production,which can be applied to modern breeding techniques such as molecular marker-assisted selection and genomic selection to achieve efficient selection and breeding.However,there are relatively few studies on genome-wide genetic variation of milk production traits in Guanzhong dairy goat population,and a lot of research is still needed to identify genetic markers affecting milk production traits and to provide a theoretical basis for molecular breeding of dairy goats.Therefore,in this study,we selected Guanzhong dairy goats for whole-genome resequencing to detect genetic variation in their genomes to investigate the effects of domestication and long-term selection on their genomes;analyzed the differences in milk yield and milk quality phenotypes of Guanzhong dairy goats,explored the genetic diversity of high and low milk yield dairy goat populations using principal component analysis and population structure analysis,and detected positive selection signals in the populations using selective sweep analysis;conducted statistical and analysis of SNP of candidate genes,explored the linkage of loci using linkage disequilibrium analysis,and analyzed and predicted the effects of nonsynonymous mutations on the protein encoded by candidate genes using bioinformatics methods,in order to reveal the important genetic variants and candidate genes leading to phenotypic advantages of milk production traits in Guanzhong dairy goats,and provide a molecular basis for selection and breed improvement of Guanzhong dairy goats.The main results of this study were obtained as follows:1.Whole-genome resequencing obtained whole-genome sequences of 20 Guanzhong dairy goats,and a total of 21324600 SNPs,2297586 In Del,128369 SVs and 749606 CNVs were detected within their whole genome.Genes such as PRL,AKT1,ACACA,ACACB and IRS2 had more variant types in the exonic region.These genes were involved in the KEGG pathways related to milk production traits such as oxytocin signaling pathway,insulin signaling pathway,PI3K-Akt signaling pathway and fatty acid biosynthesis.They were also involved in GO terms related to milk production traits such as secretory granule membrane,apical part of cells,endoplasmic reticulum exit site,regulation of cell development,regulation of ion transport,and calcium ion binding.It suggested that genes related to milk production may be selected in the genetic evolution of Guanzhong dairy goat population.2.The results of the analysis of variance showed that the differences in milk production of Guanzhong dairy goats were significant(P < 0.01),while milk protein rate,milk fat rate,lactose rate and non-fat solids rate did not differ significantly(P > 0.05).Genetic structure analysis of the population showed no significant genetic differentiation between high and low milk yielding Guanzhong dairy goat populations.Based on the selective sweep analysis,303 candidate genes were identified in high milk yielding dairy goats,among these genes,LEPR,DGKB,ADAMTS3,WNT3 A,ADRA1A,EPHX2,DNAJC3,PTH,HSD17B1,BRCA1,ANPEP,ALDH18A1,PRKG1,ME3,CHKA and LATS2 were associated with mammary gland development and milk production such as milk yield and milk protein;453 candidate genes were identified in low milk yielding dairy goats,among these genes,ANPEP、ADAMTS3、LALBA、ME3、PNPLA3、HSD11B1、UGDH、AGPAT2、MINPP1、AQP4、SLC51B、PRKAG1、TRPC1、TGFB2、CACNB3、MAP3K5、CPT1B、LEPR、SP1、PNPLA7 and DCHS1 related to milk production traits such as milk yield,milk protein,and milk fat.3.Selective sweep analysis revealed that 21,343,9 and 25 SNPs in the BRCA1,ALDH18A1,LALBA and PRKAG1,respectively,were selected in high or low milk yield of dairy goat populations.Among them,the SNP g.34470813C>T of ALDH18A1 and the SNP g.30455693G>A of PRKAG1 are nonsynonymous mutations.The g.34486523T>C and g.34493881A>G for ALDH18A1,g.30812604T>A and g.30812697C>T for LALBA,g.30812625A>G and g.30812738C>T for LALBA,g.30455374A>G and g.30455441G>A for PRKAG1 may be potentially linkage respectively.The p.R31 C mutation in ALDH18A1 and the p.V215 M mutation in PRKAG1 resulted in changes in physicochemical properties such as molecular weight,isoelectric point and stability and secondary structure of the protein.In summary,this study detected a large number of genetic variants in the genome of Guanzhong dairy goats by whole-genome resequencing;and screened 33 genes related to milk production traits by selective sweep analysis,including LEPR,DGKB,ADAMTS3,WNT3 A,ADRA1A,EPHX2,DNAJC3,LALBA,ME3,PNPLA3,HSD11B1,UGDH,AGPAT2,MINPP1,AQP4,SLC51 B,PRKAG1,etc.;bioinformatics analysis revealed that the nonsynonymous mutation g.34470813C>T of ALDH18A1 and the nonsynonymous mutation g.30455693G>A of PRKAG1 affected the physicochemical properties and structure of the encoded proteins.The key genes and their SNP identified in this study can be used tentatively as potential molecular markers for milk production traits in Guanzhong dairy goats.