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Extensive polymorphism in the porcine Toll-like receptor 10 gene
Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV. Uppsala University.ORCID-id: 0000-0001-7888-1571
Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV. The University of Queensland, Australia.
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2012 (Engelska)Ingår i: International Journal of Immunogenetics, ISSN 1744-3121, E-ISSN 1744-313X, Vol. 39, nr 1, s. 68-76Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The great importance of the Toll-like receptors (TLRs) in innate immunity is well established, but one family member – TLR10 – remains elusive. TLR10 is expressed in various tissues in several species, but its ligand is not known and its function is still poorly understood. The open reading frame of TLR10 was sequenced in 15 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace and Large White origin. Amino acid positions corresponding to detected nonsynonymous single nucleotide polymorphisms (SNPs) were analysed in the crystal structures determined for the human TLR1–TLR2–lipopeptide complex and the human TLR10 Toll/Interleukin 1 receptor (TIR) dimer. SNP occurrence in wild boars and domestic pigs was compared, and haplotypes for the TLR10 gene and the TLR6-1-10 gene cluster were reconstructed. Despite the limited number of animals sequenced in the present study (N = 30), a larger number of SNPs were found in TLR10 than recently reported for TLR1, TLR6 and TLR2. Thirty-three SNPs were detected, of which 20 were nonsynonymous. The relative frequency of nonsynonymous (dN) and synonymous (dS) SNPs between wild boars and domestic pigs was higher in TLR10 than recently reported for TLR1, TLR6 and TLR2. However, the polymorphism reported in the present study seems to leave the function of the TLR10 molecule unaffected. Furthermore, no nonsynonymous SNPs were detected in the part of the gene corresponding to the hinge region of the receptor, probably reflecting rigorously acting functional constraint. The total number of SNPs and the number of nonsynonymous SNPs were significantly lower (< 0.05) in the wild boars than in the domestic pigs, and fewer TLR10 haplotypes were present in the wild boars. The majority of the TLR6-1-10 haplotypes were specific for either wild boars or domestic pigs, probably reflecting differences in microbial environment and population history.

Ort, förlag, år, upplaga, sidor
2012. Vol. 39, nr 1, s. 68-76
Nationell ämneskategori
Immunologi Genetik
Forskningsämne
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:lnu:diva-15033DOI: 10.1111/j.1744-313X.2011.01057.xScopus ID: 2-s2.0-84855348173OAI: oai:DiVA.org:lnu-15033DiVA, id: diva2:449052
Tillgänglig från: 2011-10-19 Skapad: 2011-10-19 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
Ingår i avhandling
1. Polymorphism in pattern recognition receptor genes in pigs
Öppna denna publikation i ny flik eller fönster >>Polymorphism in pattern recognition receptor genes in pigs
2010 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The mammalian immune defense consists of two systems, which are interconnected and co-operate to provide host defense. The innate immune system is always active and detects and responds to non-self without delay. The adaptive immune system has a lag phase, but is more specific and has got a memory.

The innate immune system relies on pattern recognition receptors (PRRs) to detect molecular patterns signaling microbial presence. This thesis focuses on a centrally placed family of PRRs, namely the Toll-like receptors (TLRs), and on mannan-binding lectin (MBL), a PRR which initiates the lectin activation pathway of complement. TLRs are expressed on the cell surface and in intracellular compartments, while MBL is a soluble protein present in most body fluids.

Polymorphism – literally ’many forms’ – refers to variation between individuals, at DNA level as well as in traits. A single nucleotide polymorphism (SNP) implicates that alternative nucleotides are present at a particular position in the genome. Mutations, together with phenomena like gene duplication and whole genome duplication, are the ultimate source of variation in nature and the fuel for evolution. Through natural selection and breeding, i.e. artificial selection, species are shaped and change over time.

Domestic animals are well suited for genetic studies, since they enable comparisons of populations exposed to different selection criteria and environmental challenges. Also, in the case of pigs, comparisons to the wild ancestor – i.e. the wild boar – can shed light on the evolutionary process. Moreover, pigs are large animal models for humans.

Paper I reports the refinement of previously identified quantitative trait loci for immune-related traits on pig chromosome 8.

Papers II and III report differences in polymorphic patterns between wild boars and domestic pigs in the TLR1, TLR2, TLR6, and TLR10 genes. In TLR1 and TLR2, more SNPs were present in the domestic pigs than in the wild boars. In TLR6, SNP numbers were similar in both animal groups, but the level of heterozygosity was higher in the domestic pigs than in the wild boars. In TLR10, again, more SNPs were present in the domestic pigs, and a higher number of non-synonymous SNPs was detected in TLR10 compared to the other genes. This might suggest redundancy for TLR10 in pigs.

Paper IV reports the presence of an SNP, previously detected in domestic pigs and assumed to affect MBL concentrations in serum, in European wild boars. Also, the connection between the presumed low-producing allele and low MBL concentration in serum was confirmed. Moreover, a novel SNP, with potential to be functionally important, was detected.

Owing to the domestication process and differences in selection pressure, differences in polymorphic patterns between wild boars and domestic pigs are not surprising. However, since breeding means choosing among genotypes, the opposite pattern – more SNPs in wild boars than in domestic pigs – would have been expected. However, the result confirms other studies, which have shown that European wild boars went through a bottle neck before domestication started. The higher number of SNPs in domestic pigs may be due to relaxed purifying selection during the domestication process.

Ort, förlag, år, upplaga, sidor
Kalmar/Växjö: Linnaeus University Press, 2010. s. 151
Serie
Linnaeus University Dissertations ; 8/2010
Nationell ämneskategori
Genetik
Forskningsämne
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
urn:nbn:se:lnu:diva-116 (URN)978-91-86491-10-9 (ISBN)
Disputation
2010-04-23, A137, Kocken, Barlastgatan 11, Kalmar, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2010-04-09 Skapad: 2010-03-17 Senast uppdaterad: 2017-02-07Bibliografiskt granskad

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Bergman, Ingrid-MariaEdman, KjellNilsson Ekdahl, KristinaRosengren, K. JohanEdfors, Inger

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