Combining genome-wide association study and transcriptome analysis to identify molecular markers and genetic basis of population-asynchronous ovarian development in Coilia nasus

Coilia nasus,a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China,possesses considerable aquacultural and economic potential.However,the species faces challenges due to significant variation in the gonadal development rate among females,resulting in inconsistent ovarian maturation times at the population level,an extended reproductive period,and limitations on fish growth rate due to ovarian prematurity.In the present study,we combined genome-wide association study(GWAS)and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms(SNPs)and candidate genes associated with population-asynchronous ovarian development in C.nasus.Genotyping of the female population based on whole-genome resequencing yielded 2120695 high-quality SNPs,39 of which were suggestively associated with ovarian development.Of note,a significant SNP peak on LG21 containing 30 suggestively associated SNPs was identified,with cpne5a determined as the causal gene of the peak.Therefore,single-marker and haplotype association analyses were performed on cpne5a,revealing four genetic markers(P<0.05)and seven haplotypes(r2>0.9)significantly associated with the phenotype.Comparative transcriptome analysis of precociously and normally maturing individuals screened out 29 and 426 overlapping differentially expressed genes in the brain and ovary,respectively,between individuals of different body sizes.Integrating the GWAS and transcriptome analysis results,this study identified genes and pathways related to hypothalamic-pituitary-gonadal axis hormone secretion,extracellular matrix,angiogenesis,and gap junctions involved in population-asynchronous ovarian development.The insights gained from this study provide a basis for a deeper understanding of the molecular mechanisms underlying ovarian development in fish and may facilitate the genetic breeding of C.nasus strains exhibiting population-synchronous ovarian development in the future.