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Comparative bioinformatics analyses of transcriptome and epigenome data using bovine model systems

Jhamat, Naveed (2019). Comparative bioinformatics analyses of transcriptome and epigenome data using bovine model systems. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880 ; 2019:15
ISBN 978-91-7760-348-1
eISBN 978-91-7760-349-8
[Doctoral thesis]

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Abstract

Bioinformatics methodology is used to understand complex biological processes in molecular biology, genetics and epigenetics. This thesis performed analysis of the complex biological processes controlling reproduction in mammals including dairy cattle. Successful fertility in dairy cattle is required for farm sustainability as it supports milk productivity and longevity. Disorder in metabolism due to higher levels of insulin during pregnancy and disturbance of immune response due to bacterial infections after calving are detrimental in reproduction. Determinants controlling these molecular mechanisms are poorly understood. To investigate these mechanisms, we performed bioinformatics analyses on data obtained from two experimental studies:

Insulin is a regulator of metabolism and conditions such as hyperinsulinemia is known to impair fertility especially during embryonic development. This study investigates the potential effect of insulin treatment on gene expression and DNA methylation patterns of bovine embryos during in vitro oocyte maturation by using the EmbryoGENE DNA Methylation Array. The results of Paper I revealed that the identified differentially methylated regions (DMRs) were correlated with differentially expressed genes involved in metabolic regulation.

Uterine diseases impair fertility in dairy cattle and Lipopolysaccharide (LPS) from gram-negative Escherichia coli, is a major source of uterine diseases by activating proinflammatory pathways. This study investigates in vitro the effects of infection by LPS on bovine endometrial epithelial cells (bEEC) mimicking in vivo processes. In Paper II, RNA Sequencing analysis revealed that LPS has significantly affected the transcriptome of bEEC, identifying more than 2000 differentially expressed genes, involved in immune response, proliferation, cell adhesion, and implantation. In Paper III, Bisulfite sequencing revealed that LPS has profoundly affected the DNA methylation pattern of bEEC. 1291 DMRs were found and their associated genes were involved in molecular processes related to proliferation, apoptosis and embryo development. In Paper IV, the enrichment of motifs within these DMRs revealed transcription factor binding sites for immunologically important transcription factors. Thus, the transcriptomics, epigenomics and bioinformatics results obtained from these analyses revealed the complexity of the regulatory transcriptional network activated during inflammation.

Authors/Creators:Jhamat, Naveed
Title:Comparative bioinformatics analyses of transcriptome and epigenome data using bovine model systems
Series/Journal:Acta Universitatis Agriculturae Sueciae (1652-6880)
Year of publishing :2019
Number:2019:15
Number of Pages:84
Papers/manuscripts:
NumberReferences
IDenise Laskowski, Patrice Humblot, Marc-Andre Sirard, Ylva Sjunnesson, Naveed Jhamat, Renee Båge, Göran Andersson (2018). DNA methylation pattern of bovine blastocysts associated to hyperinsulinemia in vitro. Molecular Reproduction & Development, DOI: 10.1002/mrd.22995.
IIYongzhi Guo, Tom Van Schaik, Naveed Jhamat, Adnan Niazi, Metasu Chanrot, Gilles Gharpigny, Jean-Francois Valarcher, Erik BongcamRudloff, Göran Andersson, Patrice Humblot. Differential gene expression in bovine endometrial epithelial cells after challenge with LPS; specific implications for embryo maternal interactions. (submitted)
IIINaveed Jhamat, Adnan Niazi, Yongzhi Guo, Shumaila Sayyab, Gavin Kelsey, Eva Ivanova, Patrice Humblot, Erik Bongcam-Rudloff, Göran Andersson. LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with endometrial function and inflammation. (manuscript)
IVNaveed Jhamat, Adnan Niazi, Yongzhi Guo, Shumaila Sayyab, Patrice Humblot, Göran Andersson, Erik Bongcam-Rudloff. Genome-wide identification of transcription factor binding sites in LPS-associated differentially methylated regions in bovine endometrial epithelial cells. (manuscript)
Place of Publication:Uppsala
Publisher:Institutionen för husdjursgenetik, Sveriges lantbruksuniversitet
ISBN for printed version:978-91-7760-348-1
ISBN for electronic version:978-91-7760-349-8
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Article category:Other scientific
Full Text Status:Public
Agris subject categories.:L Animal production > L10 Animal genetics and breeding
L Animal production > L53 Animal physiology - Reproduction
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Bioinformatics and Systems Biology (methods development to be 10203)
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Keywords:iInsulin, metabolic imbalance, RNA-Seq, LPS, endometritis, Implantation, epigenetics, RRBS, differential methylation, TFBS
URN:NBN:urn:nbn:se:slu:epsilon-e-5230
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-5230
ID Code:15924
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Institutionen för husdjursgenetik (fr.o.m. 960101)
Deposited By: SLUpub Connector
Deposited On:20 Feb 2019 11:44
Metadata Last Modified:28 Feb 2019 12:25

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