Location: Livestock Bio-SystemsTitle: Integration of gene expression profiling of hypothalamic arcuate nucleus with genome-wide associations to discover functional variants associated with age at puberty in gilts
|WIJESENA, H - University Of Nebraska|
|RIETHOVEN, J - University Of Nebraska|
|SPANGLER, MATT - University Of Nebraska|
|KACHMAN, S - University Of Nebraska|
|CIOBANU, D - University Of Nebraska|
Submitted to: Plant and Animal Genome Conference
Publication Type: Abstract Only
Publication Acceptance Date: 10/27/2017
Publication Date: 1/13/2018
Citation: Wijesena, H.R., Lents, C.A., Keel, B.N., Riethoven, J.J., Spangler, M.L., Kachman, S.D., Ciobanu, D.C. 2017. Integration of gene expression profiling of hypothalamic arcuate nucleus with genome-wide associations to discover functional variants associated with age at puberty in gilts. [abstract] In proceedings: Plant and Animal Genome Conference XXVI, San Diego, CA. 13-17 Jan.2018. Abstract W981. Available: pag.confex.com/pag/xxvi/meetingapp.cgi/paper/31862.
Technical Abstract: Age at puberty (AP) in gilts is a moderately heritable trait (h2 = 0.37) and the earliest indicator of sow reproductive longevity. Therefore, quantifying the pleiotropic sources that influence both AP and reproductive longevity is important in understanding the differences in sow fertility. In this study, we integrated genome-wide associations (GWAS), whole genome sequencing and gene expression profiling of the micro-dissected hypothalamic arcuate nucleus using RNA sequencing to identify genetic variants associated with AP in the UNL resource population (n=1,644). The arcuate nucleus plays a major role in regulating the onset of puberty through controlled secretion of gonadotropins. Seventy differentially expressed genes (DEG) were identified (Padj < 0.1) between early (n=11) and late (n=6) onset of puberty gilts. Three of these genes (CDADC1, FAM111B and HERPUD2) overlapped with major (top 1%) QTL regions for AP from GWAS. Genetic variants located upstream of transcription start site (<1000 bp) affecting potential cis-binding motifs were identified as possible sources of differential expression and variation in onset of puberty. For example, SNP-affected motifs for two transcription factors (CTCF and SP2) known to regulate the expression of both CDADC1 and FAM111B were identified in the proximal promoter of these genes. There were 363 upstream regulators of the 70 DEG identified. Thirty-eight upstream regulators of six DEG (CDKN1A, DPP4, FFAR2, LCN2, PGK1 and SAMHD1) overlapped with major QTL regions for AP. Missense SNP were identified in four regulators (APC, CDCA2, IL17B and RAD9A), which could be potential trans-modulators of DEG in gilts with differences in AP.