DNAH6: A Newly Identified Gene Improving Total Number Born with Functional Enrichment Analysis in French Large White
Lin Zhang1, Junjie Shao1, Chenchen Yang1
1College of Animal Science and Technology, Tarim University, Alar 843300, China.
None:
Reproductive characteristics in pigs exhibit low heritability levels. Performing genome-wide association studies (GWAS) to pinpoint candidate genes for these characteristics is crucial for enhancing swine fertility. In this research, hair samples were gathered from 689 French Large White sows within the primary breeding population for DNA extraction purposes. Genotyping was carried out using a 50K liquid-phase SNP chip. Four statistical approaches-MLM, CMLM, FarmCPU, and BLINK-were utilized to perform GWAS on nine reproductive characteristics: total number born (TNB), litter birth weight (LBW), number born alive (NBA), number of healthy births (NHB), number of weak piglets (NWP), number of stillbirths (NSB), number of mummies (MUM), number of deformed fetuses (NDF), and adjusted 21-day litter weight (ALW). siRNAs targeting significantly associated genes were designed, and viral transfection was employed to introduce them into the ovarian granulosa cells of Large White sows to explore gene functions; transcriptome sequencing of granulosa cells treated with DNAH6 siRNA was conducted to investigate the gene's action mechanism. The analysis indicated that both MLM and CMLM models identified a significant locus linked to the total number of piglets born, with the SNP positioned at 3-60064515, associated with the DNAH6 gene. Disruption of the DNAH6 gene notably reduced the proliferation of ovarian granulosa cells (p < 0.05). Transcriptome sequencing results suggest that DNAH6 may support the normal transcriptional activity of the cAMP signaling pathway by maintaining EP300 and CREBBP expression in porcine ovarian granulosa cells, while potentially inhibiting the anti-proliferative effects of the FoxO pathway. This potential mechanism may help sustain the proliferative ability of granulosa cells and promote normal follicular development, which may ultimately contribute to an increase in the total number of piglets born in sows. These results offer a potential candidate marker for enhancing the total number born of French Large White sows.
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