The evolution of three genes from the CONSTANS-LIKE gene family is studied in Brassica nigra. We use a combination of population genetic and phylogenetic techniques in order to assess the relative importance of selection and demography on the pattern of DNA variation. The analysis is complicated by the fact that they are recent duplicates of each other and hence there is a potential redundancy factor that has to be considered. The relationship between two of the genes, COa and COb, is however much closer than between any relationship to the third gene, COL1. The three genes are all suspected to play a part in the natural variation of flowering time of B. nigra. The thesis consists of four papers. The first paper is a technical paper concerning when and if the existence of an effective population size can be assumed. More specifically, the impact of population structure and a fluctuating (census) population size on the standard coalescent is studied. The second paper is a population genetic study of B. nigra using micro-satellites and RFLP. The resulting population genetic structure is argued to reflect the early spread of agriculture in Europe. In the third paper the general evolution of the three genes is studied. We find that not all aspects of the data could be accounted for by demography or redundancy effects, but that selection most likely played a part in the evolution of these genes. The fourth paper concerns the functional status of COb, whether it is a pseudogene or not. The most likely scenario is that COb recently became non-functional due to the fixation of a deleterious mutation during a recent bottleneck.

Lic.-avhandling Linköping : Linköpings universitet, 2006.

<p>Intresset för de naturvetenskapliga ämnena tycks under de senare åren falnat hos svenska ungdomar. En rådande uppfattning kring denna företeelse är att den grundas i de naturvetenskapliga ämnenas abstraktion, komplexitet och kunskapsmässiga omfång. Denna studie fokuserar på hur genetikområdet framställs inom tre läroböcker avsedda för biologikurs A.</p><p>Genetikområdet uppvisar samtliga av ovanstående egenskaper vilka anses vara bakomliggande denna avkylande inverkan på elevers intresse. Studien fokuserar medelst en läromedelsanalys innehållandes diskursanalytiska inslag hur ämnesområdets problematiska egenskaper materialiseras och eventuellt motverkas inom modern pedagogisk text. Från studiens redovisade resultat kan vissa gemensamma drag urskiljas i den granskade litteraturen. Däribland figurerar punkter där arbetet för konkretisering och meningskapande fallerat, vilket i dessa fall utfallit i en motsatt verkan. Från studiens resultat kan frågeställningar utveckla sig, såsom: Kan dessa fallerande punkter i kombination med den i klassrum förekommande monopolära tillämpning av läromedel resultera i en negativ synergi?</p>

<p>En vanlig åsikt bland lärare är att genetiken är ett intressant avsnitt, men att det är svårt att undervisa så eleverna förstår. Därmed är det viktigt att det bör finnas illustrativa bilder som förtydligar texten, och är pedagogiskt framställda. Som lärare är man ansvarig för lärandet, och använder olika hjälpmedel, exempelvis lärobok. Läroböckernas kvalitet är därför mycket viktig, Syftet med examensarbetet var att undersöka, hur bilderna inom genetik och genteknik presenteras i gymnasieläroböcker. Samtliga bilder analyseras och tolkas med hjälp av ett kodschema och dess tillhörande bedömningsgrunder. Analysen visade att enstaka bilder var under all kritik för att klassas som pedagogiska, men dessa bilder är av underordnad betydelse för helhetsresultatet. Det framgår att Biologiböckerna har lite högre medelvärden än Naturkunskapsböckerna. Slutsats av bildanalysen är att en stor del av bilderna (82 %) kan klassas som pedagogiska bilder i skolmiljö och att den påtagligaste skillnaden som finns mellan läromedlen är bildhänvisningen i brödtexten.</p>

Cervical cancer is the second most common cancer in women worldwide. Persistent infection by an oncogenic type of human papillomavirus (HPV) is a necessary but not sufficient cause and there is also a genetic component. This thesis aims to identify host genetic risk factors for cervical cancer based on the hypothesis that susceptibility is affected by genetic variation in the immune response towards HPV infection. Paper I analyzed allergy in sons and cervical cancer in their mothers, and revealed an inverse association between cervical cancer and allergy across generations. Mothers of allergic sons have a lower incidence of cervical cancer, supporting the importance of immunogenetic factors. Paper II investigated the HPV type in 1079 women diagnosed 1965-1993. All women were from families with at least two affected. It appeared that HPV 16 was becoming less common with time. There was no evidence that related women were prone to infection by the same type, indicating that the immunogenetic factors act in a general, rather than an HPV type specific, manner. Paper III and IV analysed the association of candidate genes with susceptibility to cervical cancer in 1306 women with cervical cancer in situ and 288 unrelated controls. Paper III showed the association of variation in the two immune response genes chemokine receptor 2 (CCR-2) and interleukin 4 receptor (IL-4R) with cervical cancer. In paper IV variation at several loci in the MHC region was studied and the importance of the HLA class II locus DQB1 emphasized. This thesis work supports the contribution of genes of the immune system to cervical cancer susceptibility. The genetic risk factors so far identified account for only a part of the genetic susceptibility, which implies that other yet undiscovered variants of importance remain to be identified.

The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune response. The IRF5 gene has received considerable attention since it was shown to be associated with two autoimmune diseases; systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The aim of this thesis was to examine if IRF5 is associated with other autoimmune diseases and to investigate the role of the genetic variation of IRF5. In the first study a set of common polymorphisms in IRF5 were analyzed for their association with two subgroup of inflammatory bowel disease (IBD); Crohn´s diseases (CD) and ulcerative colitis (UC). A strong signal of association of IRF5 with IBD was found. The most strongly associated polymorphism is a 5 base pair (bp) insertion-deletion (indel) in the promoter region of the IRF5 gene. The association was detected within both UC and CD, and appeared to be stronger in UC. In the second study we investigated the association of IRF5 with multiple sclerosis (MS). A similar set of polymorphisms as in the IBD study were genotyped in a cohort of MS patients and controls. The same polymorphisms that were associated with IBD were also found to be associated with MS. In the third study, we performed a comprehensive investigation of the IRF5 gene to detect most of the polymorphisms in the gene, and to determine to what extent they account for the association signals obtained from the gene. IRF5 was sequenced and 34 new polymorphisms were identified. Twenty seven of these, and 20 previously known SNPs in IRF5 were genotyped in an SLE case-control cohort. We found that only two polymorphisms, the 5bp indel and a SNP downstream of IRF5, account for the association signal from all the remaining markers in the IRF5 gene, and that these two polymorphisms are independently associated with SLE. Interestingly, in our studies on IBD and MS, we only observed the signal from the 5bp indel polymorphism as a risk factor for IBDs. In the fourth study the two independent risk alleles in IRF5, were tested for their association with primary Sjögren´s syndrome (pSS). In this study we also included one SNP in the STAT4 gene, since STAT4 had recently been shown to be associated with SLE. Both risk factors in IRF5 and STAT4 were found to be associated with pSS. The regulation of expression of IRF5 was also investigated in the first three studies. We observed allele-specific differences in protein binding as well as increased binding of the transcription factor SP1 to the 5bp risk allele. We also detected increased expression of the IRF5 mRNA from a promoter containing the risk allele. Taken together, the results of our studies suggest a general function for IRF5 as a regulator of the autoimmune response, where the 5bp indel is associated with IBD, MS, SLE and pSS. The additionally polymorphisms, which account for the remaining association signal obtained with SLE and pSS, may contribute to the disease manifestations that are specific for rheumatic diseases. Our studies add to the evidence that there are genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases.

In summary, this thesis presents the localisation and identification of genetic variants of which some are disease associated and some considered to be neutral. Knowledge of the basic mechanisms behind human disorders is important both from a biological and medical point of view. The thesis is based on four papers of which the first two clarify the genetic basis of autosomal dominant aplasia of lacrimal and salivary glands (ALSG). ALSG is a rare disorder with high penetrance and variable expressivity characterized by dry mouth and eyes. In paper I, we located the ALSG gene to a 22 centiMorgan region on chromosome 5 through a genome-wide linkage scan with microsatellite markers in two families. Mutations were found in the gene encoding fibroblast growth factor 10 (FGF10) situated in the linked chromosome 5 region. Mice having only one copy of the FGF10 gene (Fgf10+/- mice) have a phenotype similar to ALSG, providing an animal model for the disorder. In paper II, we describe two additional patients with ALSG and missense mutations in FGF10, providing further genotype-phenotype correlations. The aim of paper III was to identify a gene involved in autosomal recessive severe congenital neutropenia (SCN), also referred to as Kostmann syndrome. The disease is characterized by a very low absolute neutrophil count and recurrent bacterial infections. Affected individuals from the family with SCN originally described by Dr Kostmann were genotyped with whole-genome SNP arrays. Autozygosity mapping identified a shared haplotype spanning 1.2 Mb on chromosome 1q22. This region contained 37 known genes, of which several were associated with myelopoiesis. Our finding contributed to the identification of the gene mutated in Kostmann syndrome. In paper IV a cytogenetic inversion on chromosome 10 was mapped and characterized. Sequence- and haplotype analysis of carriers from four non-related Swedish families revealed identical inversion breakpoints and established that the rearrangement was identical by descent. A retrospective study of karyotypes together with screening of large sample sets established that the inversion is a rare and inherited chromosome variant with a broad geographical distribution in Sweden. No consistent phenotype was found associated with the inversion. Genetic research increases the understanding of our genomes and makes it possible to discover variants contributing to disease. Identification of such genetic variants further enables studies of gene function and pathogenesis. The finding of the disease associated variants in this thesis will eventually contribute to improved diagnosis, prognosis, risk assessment and a future treatment of patients.

En vanlig åsikt bland lärare är att genetiken är ett intressant avsnitt, men att det är svårt att undervisa så eleverna förstår. Därmed är det viktigt att det bör finnas illustrativa bilder som förtydligar texten, och är pedagogiskt framställda. Som lärare är man ansvarig för lärandet, och använder olika hjälpmedel, exempelvis lärobok. Läroböckernas kvalitet är därför mycket viktig, Syftet med examensarbetet var att undersöka, hur bilderna inom genetik och genteknik presenteras i gymnasieläroböcker. Samtliga bilder analyseras och tolkas med hjälp av ett kodschema och dess tillhörande bedömningsgrunder. Analysen visade att enstaka bilder var under all kritik för att klassas som pedagogiska, men dessa bilder är av underordnad betydelse för helhetsresultatet. Det framgår att Biologiböckerna har lite högre medelvärden än Naturkunskapsböckerna. Slutsats av bildanalysen är att en stor del av bilderna (82 %) kan klassas som pedagogiska bilder i skolmiljö och att den påtagligaste skillnaden som finns mellan läromedlen är bildhänvisningen i brödtexten.

Intresset för de naturvetenskapliga ämnena tycks under de senare åren falnat hos svenska ungdomar. En rådande uppfattning kring denna företeelse är att den grundas i de naturvetenskapliga ämnenas abstraktion, komplexitet och kunskapsmässiga omfång. Denna studie fokuserar på hur genetikområdet framställs inom tre läroböcker avsedda för biologikurs A. Genetikområdet uppvisar samtliga av ovanstående egenskaper vilka anses vara bakomliggande denna avkylande inverkan på elevers intresse. Studien fokuserar medelst en läromedelsanalys innehållandes diskursanalytiska inslag hur ämnesområdets problematiska egenskaper materialiseras och eventuellt motverkas inom modern pedagogisk text. Från studiens redovisade resultat kan vissa gemensamma drag urskiljas i den granskade litteraturen. Däribland figurerar punkter där arbetet för konkretisering och meningskapande fallerat, vilket i dessa fall utfallit i en motsatt verkan. Från studiens resultat kan frågeställningar utveckla sig, såsom: Kan dessa fallerande punkter i kombination med den i klassrum förekommande monopolära tillämpning av läromedel resultera i en negativ synergi?

Erlangen, Nürnberg, Universiẗat, Diss., 2006. / Enth. 1 Sonderabdr. aus: The journal of gene medicine ; 7. 2005. - Beitr. teilw. dt., teilw. engl.