Comparative radiation hybrid mapping and haplotype analysis of bovine TLR4 /

Bovine diseases take a heavy economic toll and are cause for public health concerns. Toll-like receptor 4 (TLR4) is a cell-surface receptor that activates innate and adaptive immune responses. Its relationship to disease in humans and mice and its high degree of functional conservation among mammals...

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Bibliographic Details
Main Author: White, Stephen Nereus
Format: Thesis Book
Language:English
Published: [Place of publication not identified] : [publisher not identified] ; 2003.
Subjects:
Online Access:http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=764884731&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD
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Summary:Bovine diseases take a heavy economic toll and are cause for public health concerns. Toll-like receptor 4 (TLR4) is a cell-surface receptor that activates innate and adaptive immune responses. Its relationship to disease in humans and mice and its high degree of functional conservation among mammals strongly suggest that TLR4 will play an important role in bovine disease resistance. In particular, TLR4 is a candidate gene for resistance to bovine shipping fever and Johne's disease because of its role in resistance to Pasteurella spp., Mycobacterium tuberculosis, and other pathogens in mice. The first steps to address the possible roles of TLR4 in bovine disease resistance are mapping and assessment of segregating variation. Comparative fine maps were constructed for the region surrounding bovine TLR4 on the distal end of bovine chromosome 8, as well as for the region surrounding a related gene, TLR2, which is located on the proximal end of bovine chromosome 17. These fine maps extend the resolution of existing comparative maps and allow TLR4 and TLR2 to be assessed for correlation with QTL. To assess segregating variation in bovine TLR4, its coding regions were sequenced in 40 individuals from 11 breeds representing 3 continents of origin. Thirty-two single nucleotide polymorphisms (SNPs) were found, of which 28 are in coding regions, for an average of one per 90 base pairs of coding sequence. This is among the highest rates reported in cattle. It is possible that a selective advantage exists for wide TLR4 variation, in order to recognize a continually evolving array of pathogens. Haplotypes were assembled for each of these individuals to produce markers for disease association testing. Coding regions were also sequenced for 7 American bison and 4 river buffalo. These data show TLR4 to be highly polymorphic in these species, in addition to establishing sequence information and providing haplotype markers. This work supplies foundational insight into TLR4 in ruminants, and provides markers for disease association studies in 3 economically important species.
Item Description:Vita.
"Major Subject: Genetics".
Physical Description:xi, 75 leaves : illustrations ; 28 cm.
Issued also on microfiche from University Microfilm Inc.
Bibliography:Includes bibliographical references (leaves 63-74).