Genetic characterization to dissect the phenotypic complexity of autoimmunity

Jenny C Karlsson

Genetic characterization to dissect the phenotypic complexity of autoimmunity

Jenny C Karlsson

Lung Biology

Research output: Thesis › Doctoral Thesis (compilation)

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Abstract

Autoimmune diseases are dependent on multiple genes and unknown environmental factors. Great efforts in the identification of genes conferring susceptibility to autoimmune diseases like Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS) have recently been rewarding. A few genes have so far been associated to several autoimmune disorders and the understanding of the role of these genes in the pathogenesis and the identification of additional genes will be of great use in the designing of new and better therapies. The fine characterization of each disease is of importance in order to define sub-groups, which may respond differently to treatments.

The work in this thesis was done in mouse models for RA and MS and is based on four papers where the aim was to identify genes associated with these diseases. We have studied crosses between a susceptible and a resistant mouse strain to assess the genetic context for a disease-linked locus to appear. In an F2 intercross between the two strains, the Eae2 locus on chromosome 15 was previously linked to disease in the MS model Experimental Autoimmune Encephalomyelitis (EAE) through interaction with Eae3 on chromosome 3. The locus homologous to Eae2 on human chromosome 5 was later associated with MS in a Finnish population. In order to identify additional loci, EAE was studied in an F2 intercross where the Eae2 locus was neutralized (paper I) and in a N2 backcross (paper II). In paper III and IV a new strategy to study the interaction between Eae2 and Eae3 is described. Mice congenic for the Eae2 and Eae3 regions were bred in a Partial Advanced Intercross (PAI), which allows for the segregation of genes in the congenic intervals. More than 1000 PAI mice were investigated for Collagen Induced Arthritis (CIA). Different traits of disease were linked to seven sub-QTL within Eae2 and Eae3. Furthermore, the importance of sub-phenotypes in order to identify disease-modifying genes was investigated and is discussed.

Original language	English
Qualification	Doctor
Awarding Institution	Department of Experimental Medical Science
Supervisors/Advisors	Andersson, Åsa, Supervisor Holmdahl, Rikard, Supervisor
Award date	2005 Nov 26
Publisher	Medical Inflammation Research, Department of Experimental Medicine, Faculty of Medicine, Lund University
ISBN (Print)	91-85481-04-1
Publication status	Published - 2005

Bibliographical note

Defence details

Date: 2005-11-26
Time: 09:00
Place: Segerfalk´s salen BMC Sölvegatan 19 221 84 Lund

External reviewer(s)

Name: Alarcón-Riquelme, Marta
Title: Professor
Affiliation: Department of genetics and pathology, Rudbeck laboratory, Uppsala, Sweden

---

<div class="article_info">Johan Jirholt, Anna-Karin Lindqvist, Jenny C Karlsson, Åsa Andersson and Rikard Holmdahl. 2002. Identification of susceptibility genes for experimental autoimmune encephalomyelitis that overcome the protective effect of Eae2 locus International Immunology, vol 14 pp 79-85.</div>
<div class="article_info">Jenny C Karlsson, X Zhao, I Lonskaya, M Neptin, R Holmdahl and Å Andersson. 2003. Novel quantitative trait loci controlling development of experimental autoimmune encephalomyelitis and proportion of lymphocyte subpopulations Journal of Immunology, vol 170 pp 1019-1026.</div>
<div class="article_info">Martina Johannesson, Jenny C Karlsson, Patrik Wernhoff, Kuttyselva Nandakumar, Anna-Karin Lindqvist, Lina Olsson, Andrew Cook, Åsa Andersson and Rikard Holmdahl. 2005. Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice Genes and Immunity, vol 6 pp 175-185.</div>
<div class="article_info">Jenny C Karlsson, Martina Johannesson, Therese Lindvall, Patrik Wernhoff, Rikard Holmdahl and Rikard Holmdahl. 2005. Genetic interactions in Eae2 control collagen induced arthritis and the CD4/CD8 T cell ratio Journal of Immunology, vol 174 pp 533-541.</div>

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Department of Experimental Medical Science (013210000), Medical Inflammation Research (013212019), Lung Biology (013212002)

Subject classification (UKÄ)

Basic Medicine

Free keywords

transplantation
Immunologi
serologi
serology
epistasis
EAE
autoimmunity
Immunology
CIA
QTL

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Jennythesis051024

Cite this

@phdthesis{1b20ff9c092043eb9bac2ed49ce96040,

title = "Genetic characterization to dissect the phenotypic complexity of autoimmunity",

abstract = "Autoimmune diseases are dependent on multiple genes and unknown environmental factors. Great efforts in the identification of genes conferring susceptibility to autoimmune diseases like Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS) have recently been rewarding. A few genes have so far been associated to several autoimmune disorders and the understanding of the role of these genes in the pathogenesis and the identification of additional genes will be of great use in the designing of new and better therapies. The fine characterization of each disease is of importance in order to define sub-groups, which may respond differently to treatments. The work in this thesis was done in mouse models for RA and MS and is based on four papers where the aim was to identify genes associated with these diseases. We have studied crosses between a susceptible and a resistant mouse strain to assess the genetic context for a disease-linked locus to appear. In an F2 intercross between the two strains, the Eae2 locus on chromosome 15 was previously linked to disease in the MS model Experimental Autoimmune Encephalomyelitis (EAE) through interaction with Eae3 on chromosome 3. The locus homologous to Eae2 on human chromosome 5 was later associated with MS in a Finnish population. In order to identify additional loci, EAE was studied in an F2 intercross where the Eae2 locus was neutralized (paper I) and in a N2 backcross (paper II). In paper III and IV a new strategy to study the interaction between Eae2 and Eae3 is described. Mice congenic for the Eae2 and Eae3 regions were bred in a Partial Advanced Intercross (PAI), which allows for the segregation of genes in the congenic intervals. More than 1000 PAI mice were investigated for Collagen Induced Arthritis (CIA). Different traits of disease were linked to seven sub-QTL within Eae2 and Eae3. Furthermore, the importance of sub-phenotypes in order to identify disease-modifying genes was investigated and is discussed.",

keywords = "transplantation, Immunologi, serologi, serology, epistasis, EAE, autoimmunity, Immunology, CIA, QTL",

author = "Karlsson, {Jenny C}",

note = "Defence details Date: 2005-11-26 Time: 09:00 Place: Segerfalk´s salen BMC S{\"o}lvegatan 19 221 84 Lund External reviewer(s) Name: Alarc{\'o}n-Riquelme, Marta Title: Professor Affiliation: Department of genetics and pathology, Rudbeck laboratory, Uppsala, Sweden --- <div class={"}article_info{"}>Johan Jirholt, Anna-Karin Lindqvist, Jenny C Karlsson, {\AA}sa Andersson and Rikard Holmdahl. 2002. Identification of susceptibility genes for experimental autoimmune encephalomyelitis that overcome the protective effect of Eae2 locus International Immunology, vol 14 pp 79-85.</div> <div class={"}article_info{"}>Jenny C Karlsson, X Zhao, I Lonskaya, M Neptin, R Holmdahl and {\AA} Andersson. 2003. Novel quantitative trait loci controlling development of experimental autoimmune encephalomyelitis and proportion of lymphocyte subpopulations Journal of Immunology, vol 170 pp 1019-1026.</div> <div class={"}article_info{"}>Martina Johannesson, Jenny C Karlsson, Patrik Wernhoff, Kuttyselva Nandakumar, Anna-Karin Lindqvist, Lina Olsson, Andrew Cook, {\AA}sa Andersson and Rikard Holmdahl. 2005. Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice Genes and Immunity, vol 6 pp 175-185.</div> <div class={"}article_info{"}>Jenny C Karlsson, Martina Johannesson, Therese Lindvall, Patrik Wernhoff, Rikard Holmdahl and Rikard Holmdahl. 2005. Genetic interactions in Eae2 control collagen induced arthritis and the CD4/CD8 T cell ratio Journal of Immunology, vol 174 pp 533-541.</div> The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Experimental Medical Science (013210000), Medical Inflammation Research (013212019), Lung Biology (013212002)",

year = "2005",

language = "English",

isbn = "91-85481-04-1",

publisher = "Medical Inflammation Research, Department of Experimental Medicine, Faculty of Medicine, Lund University",

type = "Doctoral Thesis (compilation)",

school = "Department of Experimental Medical Science",

}

TY - THES

T1 - Genetic characterization to dissect the phenotypic complexity of autoimmunity

AU - Karlsson, Jenny C

N1 - Defence details Date: 2005-11-26 Time: 09:00 Place: Segerfalk´s salen BMC Sölvegatan 19 221 84 Lund External reviewer(s) Name: Alarcón-Riquelme, Marta Title: Professor Affiliation: Department of genetics and pathology, Rudbeck laboratory, Uppsala, Sweden --- <div class="article_info">Johan Jirholt, Anna-Karin Lindqvist, Jenny C Karlsson, Åsa Andersson and Rikard Holmdahl. 2002. Identification of susceptibility genes for experimental autoimmune encephalomyelitis that overcome the protective effect of Eae2 locus International Immunology, vol 14 pp 79-85.</div> <div class="article_info">Jenny C Karlsson, X Zhao, I Lonskaya, M Neptin, R Holmdahl and Å Andersson. 2003. Novel quantitative trait loci controlling development of experimental autoimmune encephalomyelitis and proportion of lymphocyte subpopulations Journal of Immunology, vol 170 pp 1019-1026.</div> <div class="article_info">Martina Johannesson, Jenny C Karlsson, Patrik Wernhoff, Kuttyselva Nandakumar, Anna-Karin Lindqvist, Lina Olsson, Andrew Cook, Åsa Andersson and Rikard Holmdahl. 2005. Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice Genes and Immunity, vol 6 pp 175-185.</div> <div class="article_info">Jenny C Karlsson, Martina Johannesson, Therese Lindvall, Patrik Wernhoff, Rikard Holmdahl and Rikard Holmdahl. 2005. Genetic interactions in Eae2 control collagen induced arthritis and the CD4/CD8 T cell ratio Journal of Immunology, vol 174 pp 533-541.</div> The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Experimental Medical Science (013210000), Medical Inflammation Research (013212019), Lung Biology (013212002)

PY - 2005

Y1 - 2005

N2 - Autoimmune diseases are dependent on multiple genes and unknown environmental factors. Great efforts in the identification of genes conferring susceptibility to autoimmune diseases like Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS) have recently been rewarding. A few genes have so far been associated to several autoimmune disorders and the understanding of the role of these genes in the pathogenesis and the identification of additional genes will be of great use in the designing of new and better therapies. The fine characterization of each disease is of importance in order to define sub-groups, which may respond differently to treatments. The work in this thesis was done in mouse models for RA and MS and is based on four papers where the aim was to identify genes associated with these diseases. We have studied crosses between a susceptible and a resistant mouse strain to assess the genetic context for a disease-linked locus to appear. In an F2 intercross between the two strains, the Eae2 locus on chromosome 15 was previously linked to disease in the MS model Experimental Autoimmune Encephalomyelitis (EAE) through interaction with Eae3 on chromosome 3. The locus homologous to Eae2 on human chromosome 5 was later associated with MS in a Finnish population. In order to identify additional loci, EAE was studied in an F2 intercross where the Eae2 locus was neutralized (paper I) and in a N2 backcross (paper II). In paper III and IV a new strategy to study the interaction between Eae2 and Eae3 is described. Mice congenic for the Eae2 and Eae3 regions were bred in a Partial Advanced Intercross (PAI), which allows for the segregation of genes in the congenic intervals. More than 1000 PAI mice were investigated for Collagen Induced Arthritis (CIA). Different traits of disease were linked to seven sub-QTL within Eae2 and Eae3. Furthermore, the importance of sub-phenotypes in order to identify disease-modifying genes was investigated and is discussed.

AB - Autoimmune diseases are dependent on multiple genes and unknown environmental factors. Great efforts in the identification of genes conferring susceptibility to autoimmune diseases like Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS) have recently been rewarding. A few genes have so far been associated to several autoimmune disorders and the understanding of the role of these genes in the pathogenesis and the identification of additional genes will be of great use in the designing of new and better therapies. The fine characterization of each disease is of importance in order to define sub-groups, which may respond differently to treatments. The work in this thesis was done in mouse models for RA and MS and is based on four papers where the aim was to identify genes associated with these diseases. We have studied crosses between a susceptible and a resistant mouse strain to assess the genetic context for a disease-linked locus to appear. In an F2 intercross between the two strains, the Eae2 locus on chromosome 15 was previously linked to disease in the MS model Experimental Autoimmune Encephalomyelitis (EAE) through interaction with Eae3 on chromosome 3. The locus homologous to Eae2 on human chromosome 5 was later associated with MS in a Finnish population. In order to identify additional loci, EAE was studied in an F2 intercross where the Eae2 locus was neutralized (paper I) and in a N2 backcross (paper II). In paper III and IV a new strategy to study the interaction between Eae2 and Eae3 is described. Mice congenic for the Eae2 and Eae3 regions were bred in a Partial Advanced Intercross (PAI), which allows for the segregation of genes in the congenic intervals. More than 1000 PAI mice were investigated for Collagen Induced Arthritis (CIA). Different traits of disease were linked to seven sub-QTL within Eae2 and Eae3. Furthermore, the importance of sub-phenotypes in order to identify disease-modifying genes was investigated and is discussed.

KW - transplantation

KW - Immunologi

KW - serologi

KW - serology

KW - epistasis

KW - EAE

KW - autoimmunity

KW - Immunology

KW - CIA

KW - QTL

M3 - Doctoral Thesis (compilation)

SN - 91-85481-04-1

PB - Medical Inflammation Research, Department of Experimental Medicine, Faculty of Medicine, Lund University

ER -

Genetic characterization to dissect the phenotypic complexity of autoimmunity

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

UN SDGs

Access to Document

Fingerprint

Cite this