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Säll, Torbjorn
Publications (2 of 2) Show all publications
Halldén, C., Nilsson, D., Säll, T., Lind-Halldén, C., Lidén, A. C. & Ljung, R. (2012). Origin of Swedish hemophilia A mutations. Journal of Thrombosis and Haemostasis, 10(12), 2503-2511
Open this publication in new window or tab >>Origin of Swedish hemophilia A mutations
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2012 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 10, no 12, p. 2503-2511Article in journal (Refereed) Published
Abstract [en]

 Background: Hemophilia A (HA) has a high level of variation within the disease class, with more than 1000 mutations being listed in the HAMSTeRS database. At the same time a number of F8 mutations are present in specific populations at high frequencies. Objectives: The simultaneous presence of large numbers of rare mutations and a small number of high-frequency mutations raises questions about the origins of HA mutations. The present study was aimed at describing the origins of HA mutations in the complete Swedish population. The primary issue was to determine what proportion of identical mutations are identical by descent (IBD) and what proportion are attributable to recurrent mutation events. The age of IBD mutations was also determined. Patients/Methods: In Sweden, the care of HA is centralized, and the Swedish HA population consists of ∼ 750 patients from > 300 families (35% severe, 15% moderate, and 50% mild). Identical haplotypes were defined by single-nucleotide polymorphism and microsatellite haplotyping, and the ages of the mutations were estimated with estiage. Results: Among 212 presumably unrelated patients with substitution mutations, 97 (46%) had mutations in common with other patients. Haplotyping of the 97 patients showed that 47 had IBD mutations (22%) with estimated ages of between two and 35 generations. The frequency of mild disease increased with an increasing number of patients sharing the mutations. Conclusions: A majority of the IBD mutations are mild and have age estimates of a few hundred years, but some could date back to the Middle Ages.

Keywords
founder, haplotype, hemophilia A, identical by descent, recurrent mutation
National Category
Hematology
Identifiers
urn:nbn:se:hkr:diva-9964 (URN)10.1111/jth.12010 (DOI)000312539600011 ()23020595 (PubMedID)
Available from: 2012-12-23 Created: 2012-12-23 Last updated: 2019-07-03Bibliographically approved
Nilsson, D., Andiappan, A. K., Halldén, C., Yun, W. D., Säll, T., Tim, C. F. & Cardell, L.-O. (2012). Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study. BMC Medical Genetics, 13(1), 66
Open this publication in new window or tab >>Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study
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2012 (English)In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 13, no 1, p. 66-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:The Toll-like receptor proteins are important in host defense and initiation of the innate and adaptive immune responses. A number of studies have identified associations between genetic variation in the Toll-like receptor genes and allergic disorders such as asthma and allergic rhinitis. The present study aim to search for genetic variation associated with allergic rhinitis in the Toll-like receptor genes.

METHODS:A first association analysis genotyped 73 SNPs in 182 cases and 378 controls from a Swedish population. Based on these results an additional 24 SNPs were analyzed in one Swedish population with 352 cases and 709 controls and one Chinese population with 948 cases and 580 controls.

RESULTS:The first association analysis identified 4 allergic rhinitis-associated SNPs in the TLR7-TLR8 gene region. Subsequent analysis of 24 SNPs from this region identified 7 and 5 significant SNPs from the Swedish and Chinese populations, respectively. The corresponding riskassociated haplotypes are significant after Bonferroni correction and are the most common haplotypes in both populations. The associations are primarily detected in females in the Swedish population, whereas it is seen in males in the Chinese population. Further independent support for the involvement of this region in allergic rhinitis was obtained from quantitative skin prick test data generated in both populations.

CONCLUSIONS:Haplotypes in the TLR7-TLR8 gene region were associated with allergic rhinitis in one Swedish and one Chinese population. Since this region has earlier been associated with asthma and allergic rhinitis in a Danish linkage study this speaks strongly in favour of this region being truly involved in the development of this disease.

Keywords
Allergic rhinitis, Toll-like receptor, Polymorphism, Genetics, Haplotype, Case–control
National Category
Medical Genetics
Identifiers
urn:nbn:se:hkr:diva-9618 (URN)10.1186/1471-2350-13-66 (DOI)000309423900001 ()
Available from: 2012-08-23 Created: 2012-08-23 Last updated: 2018-01-12Bibliographically approved

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