| 1. |
- amundsen, silja, et al.
(författare)
-
A comprehensive screen for SNP associations on chromosome region 5q31-33 in Swedish/Norwegian celiac disease families.
- 2007
-
Ingår i: European Journal of Human genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 15:9, s. 980-987
-
Tidskriftsartikel (refereegranskat)abstract
- Celiac disease (CD) is a gluten-induced enteropathy, which results from the interplay between environmental and genetic factors. There is a strong human leukocyte antigen (HLA) association with the disease, and HLA-DQ alleles represent a major genetic risk factor. In addition to HLA-DQ, non-HLA genes appear to be crucial for CD development. Chromosomal region 5q31–33 has demonstrated linkage with CD in several genome-wide studies, including in our Swedish/Norwegian cohort. In a European meta-analysis 5q31–33 was the only region that reached a genome-wide level of significance except for the HLA region. To identify the genetic variant(s) responsible for this linkage signal, we performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families who demonstrate linkage to the region. We selected tag SNPs from a 16 Mb region representing the 95% confidence interval of the linkage peak. A total of 1404 SNPs were used for the association analysis. We identified several regions with SNPs demonstrating moderate single- or multipoint associations. However, the isolated association signals appeared insufficient to account for the linkage signal seen in our cohort. Collective effects of multiple risk genes within the region, incomplete genetic coverage or effects related to copy number variation are possible explanations for our findings.
|
|
| 2. |
- Barbron, Marie-Claude, et al.
(författare)
-
Meta and pooled analysis of European coeliac disease data
- 2003
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 11:11, s. 828-834
-
Tidskriftsartikel (refereegranskat)abstract
- Four full genome scans have been carried out by the partners of the European cluster on coeliac disease as well as follow-up studies of candidate regions. No region outside HLA showed significant linkage to the disease in any single study. We first applied a meta-analysis based on a modification of Genome Screen Meta-Analysis to take into account the different linkage statistics, the arbitrariness of bin cutoff points, as well as the sample size of each study. We then performed a pooled linkage analysis of all families and raw genotypes. Besides the HLA region, already known to harbour a risk factor for coeliac disease, both approaches leave very little doubt on the presence of a genetic risk factor in the 5q31-33 region. This region was suggested by several individual studies, but did not reach statistical values high enough to be conclusive when data sets were analysed separately.
|
|
| 3. |
- Bergman, Annika, et al.
(författare)
-
The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation
- 2001
-
Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 9:10, s. 787-793
-
Tidskriftsartikel (refereegranskat)abstract
- The most recurrent BRCA1/BRCA2 mutation in Sweden is the BRCA1 mutation 3171ins5. In the western part of Sweden this mutation accounts for as much as 77% of identified mutations in these two genes. Our aim was to analyse in detail the haplotype and founder effects of the 3171ins5 and furthermore attempt to estimate the time of origin of the mutation. In the study we included eighteen apparently unrelated families with hereditary breast and/or ovarian cancer. At least one individual in each family had previously tested positive for the 3171ins5 mutation. Polymorphic microsatellite markers were used for the haplotype analyses. The markers were located within or flanking the BRCA1 gene spanning a region of 17.3 cΜ. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cΜ was observed in the 3171ins5 carriers spanning over four markers located within or very close to the BRCA1 gene. As this haplotype was not present in any of the normal controls it is highly likely that this is a mutation identical by descent, i.e. a true founder. The results from the haplotype analyses were used to estimate the age of the mutation. Estimations based on the Pexcess and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago.
|
|
| 4. |
- de Wert, Guido, et al.
(författare)
-
Opportunistic genomic screening. Recommendations of the European Society of Human Genetics
- 2021
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 29:3, s. 365-377
-
Tidskriftsartikel (refereegranskat)abstract
- If genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that 'actionable' genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England). They argue that the opportunity should be used to routinely and systematically look for secondary findings-so-called opportunistic screening. From a normative perspective, the distinguishing characteristic of screening is not so much its context (whether public health or health care), but the lack of an indication for having this specific test or investigation in those to whom screening is offered. Screening entails a more precarious benefits-to-risks balance. The ESHG continues to recommend a cautious approach to opportunistic screening. Proportionality and autonomy must be guaranteed, and in collectively funded health-care systems the potential benefits must be balanced against health care expenditures. With regard to genome sequencing in pediatrics, ESHG argues that it is premature to look for later-onset conditions in children. Counseling should be offered and informed consent is and should be a central ethical norm. Depending on developing evidence on penetrance, actionability, and available resources, OGS pilots may be justified to generate data for a future, informed, comparative analysis of OGS and its main alternatives, such as cascade testing.
|
|
| 5. |
|
|
| 6. |
- Ladenvall, Per, 1972, et al.
(författare)
-
Genetic variation at the human tissue-type plasminogen activator (tPA) locus: haplotypes and analysis of association to plasma levels of tPA.
- 2003
-
Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 11:8, s. 603-10
-
Tidskriftsartikel (refereegranskat)abstract
- Tissue-type plasminogen activator (tPA) plays a key role in thrombus dissolution and plasma levels of tPA have been associated with cardiovascular disease. We have previously resequenced regulatory and coding regions of the human tPA gene (PLAT) and identified eight single-nucleotide polymorphisms (SNPs). In a small experimental study, four common variants were associated with invasively determined vascular tPA release rates. The aim of the present study was to investigate whether there is an association between genetic variants at this locus and plasma levels of tPA. To this end, 240 Swedish individuals without cardiovascular disease were typed for the eight SNPs and an Alu insertion polymorphism at the PLAT locus, as well as for a polymorphism in the plasminogen activator inhibitor type 1 (PAI-1) promoter (PAI-1 -675 4G>5G). Stepwise regression analysis, with established predictors of plasma tPA including plasma PAI-1 and genetic variants, showed that neither genotypes nor haplotypes were major contributors to plasma tPA. The results also showed that the level of linkage disequilibrium was high at the PLAT locus, as demonstrated by the fact that only three haplotypes had a frequency above 5%. In conclusion, in the present study neither genetic variation at the PLAT locus nor the PAI-1 -675 4G>5G polymorphism was strong predictors of plasma tPA levels, which suggests that variations in other genes contribute to the heritability of this phenotype. The results also show that three haplotypes at the PLAT locus accounted for nearly 90% of the chromosomes and that they could be defined by typing only two SNPs.
|
|
| 7. |
- Torinsson Naluai, Åsa, 1968, et al.
(författare)
-
Searching for genes influencing a complex disease: the case of coeliac disease.
- 2008
-
Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 16:5, s. 542-53
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, a few genes have been reported to be causative in inflammatory diseases. Still, we are waiting for the vast majority to be discovered. New tools for genotyping and statistical analysis have been developed and emphasis has been put on study design. Coeliac disease (CD) is a disorder, where prolamins in dietary wheat gluten and related proteins from rye or barley are not tolerated. It is one of the most common chronic diseases in humans exceeding a population prevalence of 1%. In this article, we will summarise what is currently known about the genetics influencing CD with the emphasis on the non-HLA genetic component. We will discuss some difficulties when searching for susceptibility genes in disorders with complex inheritance patterns.
|
|
