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Sheep CIS-Regulatory Element Polymorphisms Confer Resilience in Ovine Lentivirus Infection.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Sheep CIS-Regulatory Element Polymorphisms Confer Resilience in Ovine Lentivirus Infection./
Author:	Massa, Alisha Therese.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	142 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-03, Section: B.
Contained By:	Dissertations Abstracts International83-03B.
Subject:	Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28414746
ISBN:	9798538115679

Sheep CIS-Regulatory Element Polymorphisms Confer Resilience in Ovine Lentivirus Infection.
Massa, Alisha Therese.

Sheep CIS-Regulatory Element Polymorphisms Confer Resilience in Ovine Lentivirus Infection. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 142 p.

Source: Dissertations Abstracts International, Volume: 83-03, Section: B.

Thesis (Ph.D.)--Washington State University, 2021.

This item must not be sold to any third party vendors.

Ovine progressive pneumonia is an incurable, slowly fatal infection that affects up to half of all flocks in the United States, caused by ovine lentivirus. Sheep suffer debilitating pneumonia, arthritis, encephalitis, and mastitis. Infection causes significant losses to all aspects of sheep production endangering supply of meat, milk, and wool products for human consumption. Identification of host factors that decrease susceptibility to infectious disease is a key step in combating ovine lentivirus and other retroviruses such as human immunodeficiency virus. We built upon previous work that detected a genomic region at four zinc finger genes ZNF389, ZNF192, ZSCAN16, and ZNF165 as strongly associated with 50% reduction in proviral load. Since proviral load is correlated with severity of disease and lifespan in production flocks, the aim was to find genetic variants to predict this resilient phenotype and that may be causal mutations. DNA regulatory elements in sheep macrophages were annotated because most mutations responsible for phenotypic consequences are found within these elements. Alveolar macrophages function in innate and adaptive immunity as well as wound healing in the lungs dependent on tissue-specific gene expression under epigenetic regulation. The functional diversity of tissue-resident macrophages highlights the need to study tissue-specific regulatory elements that control gene expression. This study reported the first genome-wide survey of regulatory elements in any sheep immune cell, specifically those enriched for H3K4me3 (active promoters), H3K27ac (active enhancers), H3K4me1 (enhancers), CTCF (domain anchors), and H3K27me3 (silencers) which allowed assignment of putative biological function to 12% of the sheep genome. This annotation of transcriptional regulatory elements in target tissues will aid researchers in identifying genetic mutations of immunological consequence for many infectious diseases. A haplotype cluster of at least ten small DNA polymorphisms within the active cis-regulatory elements for ZNF389 were significantly associated with the resilient phenotype to ovine lentivirus in multiple sheep populations. Other zinc finger transcription factors, like ZAP, have been implicated in restriction of retroviral replication from several host species. These data will empower research into functional mutations at sheep regulatory elements and development of marker-assisted selection schemes to develop disease-resilient production flocks.

ISBN: 9798538115679Subjects--Topical Terms:

530508
Genetics.
Subjects--Index Terms:

Epigenetics

Sheep CIS-Regulatory Element Polymorphisms Confer Resilience in Ovine Lentivirus Infection.
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300 $a 142 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-03, Section: B.
500 $a Advisor: White, Stephen N.;Neibergs, Holly L.
502 $a Thesis (Ph.D.)--Washington State University, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a Ovine progressive pneumonia is an incurable, slowly fatal infection that affects up to half of all flocks in the United States, caused by ovine lentivirus. Sheep suffer debilitating pneumonia, arthritis, encephalitis, and mastitis. Infection causes significant losses to all aspects of sheep production endangering supply of meat, milk, and wool products for human consumption. Identification of host factors that decrease susceptibility to infectious disease is a key step in combating ovine lentivirus and other retroviruses such as human immunodeficiency virus. We built upon previous work that detected a genomic region at four zinc finger genes ZNF389, ZNF192, ZSCAN16, and ZNF165 as strongly associated with 50% reduction in proviral load. Since proviral load is correlated with severity of disease and lifespan in production flocks, the aim was to find genetic variants to predict this resilient phenotype and that may be causal mutations. DNA regulatory elements in sheep macrophages were annotated because most mutations responsible for phenotypic consequences are found within these elements. Alveolar macrophages function in innate and adaptive immunity as well as wound healing in the lungs dependent on tissue-specific gene expression under epigenetic regulation. The functional diversity of tissue-resident macrophages highlights the need to study tissue-specific regulatory elements that control gene expression. This study reported the first genome-wide survey of regulatory elements in any sheep immune cell, specifically those enriched for H3K4me3 (active promoters), H3K27ac (active enhancers), H3K4me1 (enhancers), CTCF (domain anchors), and H3K27me3 (silencers) which allowed assignment of putative biological function to 12% of the sheep genome. This annotation of transcriptional regulatory elements in target tissues will aid researchers in identifying genetic mutations of immunological consequence for many infectious diseases. A haplotype cluster of at least ten small DNA polymorphisms within the active cis-regulatory elements for ZNF389 were significantly associated with the resilient phenotype to ovine lentivirus in multiple sheep populations. Other zinc finger transcription factors, like ZAP, have been implicated in restriction of retroviral replication from several host species. These data will empower research into functional mutations at sheep regulatory elements and development of marker-assisted selection schemes to develop disease-resilient production flocks.
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650 4 $a Genetics. $3 530508
650 4 $a Immunology. $3 611031
650 4 $a Veterinary services. $3 3433982
650 4 $a Infectious diseases. $3 2179310
650 4 $a Viruses. $3 571474
650 4 $a Stem cells. $3 767761
650 4 $a Mutation. $3 837917
653 $a Epigenetics
653 $a Genomic annotation
653 $a Lentivirus
653 $a Maedi-visna
653 $a Sheep
653 $a Viral restriction
690 $a 0778
690 $a 0369
690 $a 0982
710 2 $a Washington State University. $b College of Veterinary Medicine. $3 3680669
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791 $a Ph.D.
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793 $a English
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