Identifying candidate genes associated with sperm morphology abnormalities using weighted single-step GWAS in a Duroc boar population

Zhao, Yunxiang; Gao, Ning; Li, Xinyun; El‐Ashram, Saeed; Wang, Zhiquan; Zhu, Lin; Peng, Xing; Zhang, Conglin; Chen, Yilong; Li, Zhili

doi:10.1016/j.theriogenology.2019.08.031

Cited by 28 publications

(21 citation statements)

References 44 publications

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“…Our findings show that the ROBO1 gene is enriched in the axon guidance pathway (ssc04360) and 12 GO terms involved in biological functions, such as "cell motility", "signal transduction", and "protein modification process". In a recent study, it has been reported that the axon guidance pathway has a potential biological function in boar fertility [53], and its pathway has a significant role in DNA methylation alterations in sperm cell development [54]. In the current study, it seems that the TT genotype of the ROBO1 gene polymorphism might increase the sperm susceptibility to cryo-induced DNA fragmentation, as shown in the poor freezability ejaculates.…”

Section: Snp Associations With Post-thaw Semen Qualitymentioning

confidence: 52%

Gene Polymorphisms in Boar Spermatozoa and Their Associations with Post-Thaw Semen Quality

Mańkowska

Brym

Paukszto

et al. 2020

IJMS

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Genetic markers have been used to assess the freezability of semen. With the advancement in molecular genetic techniques, it is possible to assess the relationships between sperm functions and gene polymorphisms. In this study, variant calling analysis of RNA-Seq datasets was used to identify single nucleotide polymorphisms (SNPs) in boar spermatozoa and to explore the associations between SNPs and post-thaw semen quality. Assessment of post-thaw sperm quality characteristics showed that 21 boars were considered as having good semen freezability (GSF), while 19 boars were classified as having poor semen freezability (PSF). Variant calling demonstrated that most of the polymorphisms (67%) detected in boar spermatozoa were at the 3’-untranslated regions (3’-UTRs). Analysis of SNP abundance in various functional gene categories showed that gene ontology (GO) terms were related to response to stress, motility, metabolism, reproduction, and embryo development. Genomic DNA was isolated from sperm samples of 40 boars. Forty SNPs were selected and genotyped, and several SNPs were significantly associated with motility and membrane integrity of frozen-thawed (FT) spermatozoa. Polymorphism in SCLT1 gene was associated with significantly higher motility and plasma membrane integrity of FT spermatozoa from boars of the GSF group compared with those of the PSF group. Likewise, polymorphisms in MAP3K20, MS4A2, and ROBO1 genes were significantly associated with reduced cryo-induced lipid peroxidation and DNA damage of FT spermatozoa from boars of the GSF group. Candidate genes with significant SNP associations, including APPL1, PLBD1, FBXO16, EML5, RAB3C, OXSR1, PRICKLE1, and MAP3K20 genes, represent potential markers for post-thaw semen quality, and they might be relevant for future improvement in the selection procedure of boars for cryopreservation. The findings of this study provide evidence indicating that polymorphisms in genes expressed in spermatozoa could be considered as factors associated with post-thaw semen quality.

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Section: Snp Associations With Post-thaw Semen Qualitymentioning

confidence: 52%

Gene Polymorphisms in Boar Spermatozoa and Their Associations with Post-Thaw Semen Quality

Mańkowska

Brym

Paukszto

et al. 2020

IJMS

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“…This is the case for the SSC1 I6 QTL, associated to NABN, which mapped 335 kbp downstream from a QTL associated to sperm abnormalities and motility in boars (Marques et al, 2018). The QTL SSC3 I2, associated to NABN lies 350 kpb upstream from a PDROP QTL (Zhao et al, 2020). The SSC4 I1 QTL, associated to ACRO_5, resides 655 kpb upstream from a QTL for the Distal Midpiece Reflex (Zhao et al, 2020) and the SSC7 I1 QTL, associated to MT_5 maps 123 kpb upstream from a PDROP QTL (Zhao et al, 2020).…”

Section: Gwas Analysismentioning

confidence: 90%

“…Investigating the genomic regions and molecular processes controlling sperm quality has become a focus of interest in human and in livestock including swine, in this case for its relevance on the sustainability of pig breeding and production (Diniz et al, 2014;Gao et al, 2019;Marques et al, 2018;Zhao et al, 2020;Zhao et al, 2016). In fact, our results as well as data obtained by other groups (Diniz et al, 2014;Marques et al, 2018;Smital et al, 2005;Wolf, 2009), have shown that boar sperm quality has a genetic basis and that it can thus be selected for breeding strategies.…”

Section: Gwas Analysismentioning

confidence: 99%

“…The QTL SSC3 I2, associated to NABN lies 350 kpb upstream from a PDROP QTL (Zhao et al, 2020). The SSC4 I1 QTL, associated to ACRO_5, resides 655 kpb upstream from a QTL for the Distal Midpiece Reflex (Zhao et al, 2020) and the SSC7 I1 QTL, associated to MT_5 maps 123 kpb upstream from a PDROP QTL (Zhao et al, 2020). The discrepancies across studies could arise due to different technical (e.g.…”

Section: Gwas Analysismentioning

confidence: 99%

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An integrative systems biology approach to identify the molecular basis of sperm quality in swine

Gòdia

Reverter

González-Prendes

et al. 2020

Preprint

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Background:Genetic pressure in animal breeding is sparking the interest to select for elite boars with higher sperm quality to maximize ejaculate doses and fertility rates. However, the molecular basis of sperm quality remains largely unexplored. In this study, we sought to identify candidate genes, pathways and DNA variants associated to sperm quality in swine by analyzing 25 sperm-related phenotypes using a systems biology approach that integrates GWAS and RNA-seq.Results:By GWAS, we identified 12 QTL regions associated to the percentage of head and neck abnormalities, abnormal acrosomes and motile spermatozoa. Candidate genes included CHD2, KATNAL2, SLC14A2 or ABCA1. By RNA-seq, we detected 6,128 significant correlations between sperm traits and gene RNA abundances. We built a gene interaction network with the GWAS and the RNA-seq data. To build a robust gene interaction network, only the pair-wise interactions present in both the genetic co-association and the RNA co-abundance network were kept. Moreover, we also included to the Final Network both the genes which RNA abundances correlated with more than 4 semen traits as well as the miRNAs interacting with the genes on the network. The Final Network was enriched for genes involved in gamete generation and development, meiotic cell cycle, DNA repair or embryo implantation. We finally designed a panel of 73 SNPs provided from the GWAS, eGWAS and the Final Network, that explains between 5 to 36% of the phenotypic variance of the sperm traits.Conclusions:By means of a systems biology approach, we identified potential key genes affecting sperm quality. Furthermore, we propose a SNP panel that might explain a substantial part of the genetic variance for semen quality in swine and may thus be of interest for the pig breeding sector.

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“…Most of it needs to be further con rmed and investigated. Among those signi cant differential express genes, RET was recognized oncogene, MAPK4 were components of MAPK pathway, SPEF1 and SPATA2 involved in spermatogenesis may partly account for the PELP1 that was found to be a biological marker of sperm morphology abnormalities [39], NRG2 was participated in the EGFR TKI drug resistance.…”

Section: Discussionmentioning

confidence: 99%

PELP1 expressed in non-small cell lung cancer and promotes tumor cell proliferation, metastasis, and drug resistance through MAPK signaling pathway.

Wang

Ying

Liang

2020

Preprint

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Background Lung cancer is one of the tumors with high morbidity and mortality among males and females worldwide. Proline-, glutamic acid-, and leucine-rich protein 1(PELP1) is an estrogen receptor coactivator and functions as a scaffolding protein. Its oncogenic signaling was involved in the progression of several cancers. However, there is little known about the role of PELP1 in the lung cancer. The aim of this study is to explore the role of PELP1 in non-small cell lung cancer. Methods The expression of PELP1 in microarrays of lung cancer tissue and correlation with clinicopathological parameters were performed. RNA interference technology was used to downregulate PELP1 expression in A549 lung cancer cells and the tumor cell’s ability of proliferation, migration, invasion was detected by Cell Count Kit-8 and trans-well essay. In addition, whole genome exon was analyzed by poly-A RNA-sequencing. Results Results showed that PELP1 is overexpressed in the lung cancer specimens and its expression correlate with histological type, smoking status, and EGFR status but no significant prognostic value. Knockdown of PELP1 inhibited cell proliferation, migration, invasion of lung cancer cells. Furthermore, silencing PELP1 in lung tumor cells promotes the sensitivity of tumor cells to the tyrosine kinase inhibitor Gefitinib. RNA-sequencing and Western-blotting found that 140 genes were up-regulated and 143 genes were down-regulated in PELP1 silenced lung adenocarcinoma cells, which mainly affected the mitogen-activated protein kinase (MAPK) signal pathway, EGFR tyrosine kinase inhibitor resistance, PPAR signaling pathway, Cytosolic DNA-sensing pathway, cytokine-cytokine receptor interaction, drug metabolism, cAMP signaling pathway, RIG-1-like receptor signaling pathway. Conclusions PELP1 plays a key role in non-small cell lung cancer proliferation, progression, and drug resistance. These results suggest that PELP1 could be a potential target for therapeutic intervention for lung cancer.

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Identifying candidate genes associated with sperm morphology abnormalities using weighted single-step GWAS in a Duroc boar population

Cited by 28 publications

References 44 publications

Gene Polymorphisms in Boar Spermatozoa and Their Associations with Post-Thaw Semen Quality

Gene Polymorphisms in Boar Spermatozoa and Their Associations with Post-Thaw Semen Quality

An integrative systems biology approach to identify the molecular basis of sperm quality in swine

PELP1 expressed in non-small cell lung cancer and promotes tumor cell proliferation, metastasis, and drug resistance through MAPK signaling pathway.

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