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  • 1.
    Bergman, Ingrid-Maria
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Polymorphism in pattern recognition receptor genes in pigs2010Doktorsavhandling, 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.

  • 2.
    Bergman, Ingrid-Maria
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Toll-like receptors (TLRs) and mannan-binding lectin (MBL): On constant alert in a hostile environment2011Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, nr 2, s. 90-99Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    In the beginning were neither B cells nor T cells nor antibodies, but innate immune defense alone. The primary functional theme of innate immunity is the distinction between self and non-self, which is maintained by a vast number of cellular and subcellular components. In this context, the immense importance of the Toll-like receptors (TLRs) is well established. Positive (Darwinian) selection seems to be acting on the ligand-binding domains of these molecules, suggesting a selection pattern similar to that previously observed in the MHC proteins. In sharp contrast to TLRs, the biological significance of mannan-binding lectin (MBL) is controversial, and, concerning humans, it has been suggested that low concentration of MBL in serum represents a selective advantage. In this mini-review, based on a doctoral thesis, evolutionary aspects of TLRs and MBL are discussed.

  • 3.
    Bergman, Ingrid-Maria
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Edman, Kjell
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Nilsson Ekdahl, Kristina
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV. Uppsala University.
    Rosengren, K. Johan
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV. The University of Queensland, Australia.
    Edfors, Inger
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Extensive polymorphism in the porcine Toll-like receptor 10 gene2012Ingår i: International Journal of Immunogenetics, ISSN 1744-3121, E-ISSN 1744-313X, Vol. 39, nr 1, s. 68-76Artikel i tidskrift (Refereegranskat)
    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.

  • 4.
    Bergman, Ingrid-Maria
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Edman, Kjell
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Rosengren, K. Johan
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Edfors, Inger
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR)1, TLR2, TLR6, and TLR10 genes.2010Ingår i: International Symposium on Animal Genomics for Animal Health Paris, France, 31 May – 2 June 2010: The AGAH 2010 Abstract Book, 2010, s. 35-Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    The Toll-like receptors (TLR) are vitally important pattern recognition receptors linking innate and adaptive immunity. Several single nucleotide polymorphisms (SNP) in human TLR genes have been associated with disease. There are few studies on associations between polymorphisms in TLR genes and disease in pigs, but the TLR2/TLR6 heterodimer is activated by Mycoplasma hyopneumoniae, and the expression of TLR2, TLR4, and TLR9 is modulated in the presence of different Salmonella serovars. Porcine TLR1, TLR6, and TLR10 are located in a cluster on the p arm of chromosome 8, while TLR2 resides on the q arm. Previously, we identified quantitative trait loci (QTL) for immune-related traits on pig chromosome 8, close to the KIT gene and the microsatellite S0225, respectively. In order to explore polymorphism in some TLR genes in European wild boars and domestic pigs, TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 domestic pigs of Hampshire, Landrace, and Large White origin. Similarly, TLR10 was sequenced in 15 wild boars and 15 domestic pigs. In TLR1 and TLR2, more SNP 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 SNP were present in the domestic pigs, and a higher number of nonsynonymous SNP were detected in TLR10 compared to the other genes. This may suggest redundancy for TLR10 in pigs. 

  • 5.
    Bergman, Ingrid-Maria
    et al.
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Johansson, Amelie
    Edfors-Lilja, Inger
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Polymorphisms in porcine TLR1, TLR2, and TLR62008Konferensbidrag (Refereegranskat)
  • 6.
    Bergman, Ingrid-Maria
    et al.
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Johansson, Amelie
    Fossum, Caroline
    Andersson, Leif
    Edfors-Lilja, Inger
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Genetic analysis of porcine TLR genes2007Konferensbidrag (Refereegranskat)
  • 7.
    Bergman, Ingrid-Maria
    et al.
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Johansson, Amelie
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Wattrang, Eva
    Fossum, Caroline
    Andersson, Leif
    Edfors, Inger
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Refined analysis of quantitative trait loci (QTLs) for immune capacity related traits on pig chromosome 8Manuskript (preprint) (Övrigt vetenskapligt)
  • 8.
    Bergman, Ingrid-Maria
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Rosengren, K. Johan
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Edman, Kjell
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Edfors, Inger
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes2010Ingår i: Immunogenetics, ISSN 0093-7711, E-ISSN 1432-1211, Vol. 62, nr 1, s. 49-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During the last decade, the Toll-like receptors (TLRs) have been extensively studied and their immense importance in innate immunity is now being unveiled. Here, we report pronounced differences – probably reflecting the domestication process and differences in selective pressure – between wild boars and domestic pigs regarding single nucleotide polymorphisms (SNPs) in TLR genes. The open reading frames of TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace, and Large White origin. In total, 20, 27, and 26 SNPs were detected in TLR1, TLR2, and TLR6, respectively. In TLR1 and TLR2, the numbers of SNPs detected were significantly lower (P ≤ 0.05, P ≤ 0.01) in the wild boars than in the domestic pigs. In the wild boars, one major high frequency haplotype was found in all three genes, while the same pattern was exhibited only by TLR2 in the domestic pigs. The relative frequency of non-synonymous (dN) and synonymous (dS) SNPs was lower for the wild boars than for the domestic pigs in all three genes. In addition, differences in diversity between the genes were revealed: the mean heterozygosity at the polymorphic positions was markedly lower in TLR2 than in TLR1 and TLR6. Because of its localization – in proximity of the bound ligand – one of the non-synonymous SNPs detected in TLR6 may represent species-specific function on the protein level. Furthermore, the codon usage pattern in the genes studied deviated from the general codon usage pattern in Sus scrofa.

  • 9.
    Bergman, Ingrid-Maria
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Sandholm, Kerstin
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Juul-Madsen, Helle R.
    Heegaard, Peter M.
    Nilsson Ekdahl, Kristina
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Edfors, Inger
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    MBL-A concentrations and MBL1 genotypes in European wild boars, Large White pigs, and wild boar/Large White crossbreds2010Ingår i: 8th European Colloquium on Acute Phase Proteins in Helsinki, 2010.08.25-2010.08.27, 2010, s. 25-26Konferensbidrag (Refereegranskat)
  • 10.
    Bergman, Ingrid-Maria
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB). Aarhus University, Denmark.
    Sandholm, Kerstin
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Nilsson Ekdahl, Kristina
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB). Uppsala university.
    Okumura, Naohiko
    Institute of Society for Techno-innovation of Agriculture, Japan.
    Uenishi, Hirohide
    National Institute of Agrobiological Sciences, Japan.
    Guldbrandtsen, Bernt
    Aarhus University, Denmark.
    Essler, Sabine
    Univ of Veterinary Medicine, Austria.
    Knoll, Ales
    Mendel University, Czech Republic.
    Heegaard, Peter
    Technical University of Denmark, Denmark.
    Edfors, Inger
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Juul-Madsen, Helle
    Aarhus University, Denmark.
    MBL1 genotypes in wild boar populations from Sweden, Austria, the Czech Republic and Japan2013Ingår i: International Journal of Immunogenetics, ISSN 1744-3121, E-ISSN 1744-313X, Vol. 40, nr 2, s. 131-139Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The single nucleotide polymorphism (SNP) G949T in the mannose-binding lectin (MBL) 1 gene has been associated with low MBL-A concentration in serum and detected at different frequencies in various European pig populations. However, the origin of this SNP is not known. Part of the MBL1 gene was sequenced in 12 wild boar/Large White crossbred pigs from the second backcross (BC 2) generation in a family material originating from two wild boar x Large White intercrosses. Also, MBL-A serum concentration was measured in the entire BC 2 generation (n = 45). Furthermore, the genotypes of 68 wild boars from Sweden, Austria, the Czech Republic, and Japan were determined in regard to five previously described SNPs in MBL1. The T allele of G949T was present among the BC 2 animals. MBL-A serum concentration in the BC 2 animals showed a bimodal distribution, with one-third of the animals at levels between 0.7 and 1.6 μg mL−1 and the remaining pigs at levels around 13 μg mL−1. There was a co-variation between the presence of the T allele and low MBL-A concentration in serum. The genotyping of the wild boars revealed differences between populations. The T allele of G949T was not detected in the Austrian and Japanese samples and is thus unlikely to be an original feature of wild boars. In contrast, it was present at high frequency (0.35) among the Swedish wild boars, probably representing a founder effect. Five MBL1 haplotypes were resolved. Only two of these were present among the Japanese wild boars compared to four in each of the European populations. This difference may reflect differences in selection pressure and population history.

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