Evolution of MHC Genes and MHC Gene Expression
Polymorphism in coding regions and regions controlling gene expression is the major determinant of adaptive differences in natural populations. Genes of the major histocompatibility complex (MHC) possess a high level of genetic variation, which is maintained by selection over long coalescence times....
Main Author: | |
---|---|
Format: | Doctoral or Postdoctoral Thesis |
Language: | English |
Published: |
Uppsala universitet, Evolutionsbiologi
2010
|
Subjects: | |
Online Access: | http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122011 |
id |
ftuppsalauniv:oai:DiVA.org:uu-122011 |
---|---|
record_format |
openpolar |
spelling |
ftuppsalauniv:oai:DiVA.org:uu-122011 2023-05-15T15:51:11+02:00 Evolution of MHC Genes and MHC Gene Expression Berggren Bremdal, Karin 2010 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122011 eng eng Uppsala universitet, Evolutionsbiologi Uppsala : Acta Universitatis Upsaliensis Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 736 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122011 urn:isbn:978-91-554-7792-9 info:eu-repo/semantics/openAccess major histocompatibilty complex dog leukocyte antigen balancing selection linkage disequilibrium promoter diabetes mellitus Canis familiaris Canis lupus Erinaceus europaeus Erinaceus concolor Genetics Genetik Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2010 ftuppsalauniv 2023-02-23T21:43:45Z Polymorphism in coding regions and regions controlling gene expression is the major determinant of adaptive differences in natural populations. Genes of the major histocompatibility complex (MHC) possess a high level of genetic variation, which is maintained by selection over long coalescence times. MHC genes encode antigen-presenting molecules in the adaptive immune system, which protects the host from infectious diseases. However, MHC molecules may also present self-peptides and for most autoimmune diseases there is a genetic factor associated with the MHC. MHC genes have been used to learn about the interplay of selection and historical population events. In domestic dogs and their progenitor, the wolf, I explored factors associated with domestication and breed formation and their influence not only on MHC coding regions but also on the haplotypic structure of the class II region. Polymorphism and strong selection was demonstrated in the proximal promoters of MHC genes in dogs and wolves. Hence, genetic variation associated with MHC gene expression may have at least equal importance for a well functioning immune system. Associations between promoter sequences and particular coding alleles suggested allele-specific expression patterns. SNP haplotypes of the MHC class II region revealed ancestral as well as convergent haplotypes, in which combinations of alleles are kept by selection. Interestingly, weaker allelic associations were found between different genes and between coding regions and promoters in dogs compared to wolves. Potentially, this could cause insufficient defense against infections and predispose dogs to autoimmune diseases. For example, I identified a site in the promoter region that showed a consistent difference between haplotypes conferring susceptibility and protection to diabetes in dogs, which should be investigated further. Furthermore, I investigated how selection and demographic changes associated with glacial and inter-glacial periods have affected MHC variation in European hedgehogs ... Doctoral or Postdoctoral Thesis Canis lupus Uppsala University: Publications (DiVA) |
institution |
Open Polar |
collection |
Uppsala University: Publications (DiVA) |
op_collection_id |
ftuppsalauniv |
language |
English |
topic |
major histocompatibilty complex dog leukocyte antigen balancing selection linkage disequilibrium promoter diabetes mellitus Canis familiaris Canis lupus Erinaceus europaeus Erinaceus concolor Genetics Genetik |
spellingShingle |
major histocompatibilty complex dog leukocyte antigen balancing selection linkage disequilibrium promoter diabetes mellitus Canis familiaris Canis lupus Erinaceus europaeus Erinaceus concolor Genetics Genetik Berggren Bremdal, Karin Evolution of MHC Genes and MHC Gene Expression |
topic_facet |
major histocompatibilty complex dog leukocyte antigen balancing selection linkage disequilibrium promoter diabetes mellitus Canis familiaris Canis lupus Erinaceus europaeus Erinaceus concolor Genetics Genetik |
description |
Polymorphism in coding regions and regions controlling gene expression is the major determinant of adaptive differences in natural populations. Genes of the major histocompatibility complex (MHC) possess a high level of genetic variation, which is maintained by selection over long coalescence times. MHC genes encode antigen-presenting molecules in the adaptive immune system, which protects the host from infectious diseases. However, MHC molecules may also present self-peptides and for most autoimmune diseases there is a genetic factor associated with the MHC. MHC genes have been used to learn about the interplay of selection and historical population events. In domestic dogs and their progenitor, the wolf, I explored factors associated with domestication and breed formation and their influence not only on MHC coding regions but also on the haplotypic structure of the class II region. Polymorphism and strong selection was demonstrated in the proximal promoters of MHC genes in dogs and wolves. Hence, genetic variation associated with MHC gene expression may have at least equal importance for a well functioning immune system. Associations between promoter sequences and particular coding alleles suggested allele-specific expression patterns. SNP haplotypes of the MHC class II region revealed ancestral as well as convergent haplotypes, in which combinations of alleles are kept by selection. Interestingly, weaker allelic associations were found between different genes and between coding regions and promoters in dogs compared to wolves. Potentially, this could cause insufficient defense against infections and predispose dogs to autoimmune diseases. For example, I identified a site in the promoter region that showed a consistent difference between haplotypes conferring susceptibility and protection to diabetes in dogs, which should be investigated further. Furthermore, I investigated how selection and demographic changes associated with glacial and inter-glacial periods have affected MHC variation in European hedgehogs ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Berggren Bremdal, Karin |
author_facet |
Berggren Bremdal, Karin |
author_sort |
Berggren Bremdal, Karin |
title |
Evolution of MHC Genes and MHC Gene Expression |
title_short |
Evolution of MHC Genes and MHC Gene Expression |
title_full |
Evolution of MHC Genes and MHC Gene Expression |
title_fullStr |
Evolution of MHC Genes and MHC Gene Expression |
title_full_unstemmed |
Evolution of MHC Genes and MHC Gene Expression |
title_sort |
evolution of mhc genes and mhc gene expression |
publisher |
Uppsala universitet, Evolutionsbiologi |
publishDate |
2010 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122011 |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_relation |
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 736 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122011 urn:isbn:978-91-554-7792-9 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1766386246934855680 |