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- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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- Åberg, Anna, et al.
(författare)
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Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
- 2017
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
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Tidskriftsartikel (refereegranskat)abstract
- The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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- Bilde, T., et al.
(författare)
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The genetic architecture of fitness in a seed beetle : assessing the potential for indirect genetic benefits of female choice
- 2008
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 8, s. 295-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Quantifying the amount of standing genetic variation in fitness represents an empirical challenge. Unfortunately, the shortage of detailed studies of the genetic architecture of fitness has hampered progress in several domains of evolutionary biology. One such area is the study of sexual selection. In particular, the evolution of adaptive female choice by indirect genetic benefits relies on the presence of genetic variation for fitness. Female choice by genetic benefits fall broadly into good genes (additive) models and compatibility (non-additive) models where the strength of selection is dictated by the genetic architecture of fitness. To characterize the genetic architecture of fitness, we employed a quantitative genetic design (the diallel cross) in a population of the seed beetle Callosobruchus maculatus, which is known to exhibit post-copulatory female choice. From reciprocal crosses of inbred lines, we assayed egg production, egg-to-adult survival, and lifetime offspring production of the outbred F1 daughters (F1 productivity). Results: We used the bio model to estimate six components of genetic and environmental variance in fitness. We found sizeable additive and non-additive genetic variance in F-1 productivity, but lower genetic variance in egg-to-adult survival, which was strongly influenced by maternal and paternal effects. Conclusion: Our results show that, in order to gain a relevant understanding of the genetic architecture of fitness, measures of offspring fitness should be inclusive and should include quantifications of offspring reproductive success. We note that our estimate of additive genetic variance in F-1 productivity (CVA = 14%) is sufficient to generate indirect selection on female choice. However, our results also show that the major determinant of offspring fitness is the genetic interaction between parental genomes, as indicated by large amounts of non-additive genetic variance (dominance and/or epistasis) for F-1 productivity. We discuss the processes that may maintain additive and non-additive genetic variance for fitness and how these relate to indirect selection for female choice.
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- Landin-Olsson, M., et al.
(författare)
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Islet cell and thyrogastric antibodies in 633 consecutive 15- to 34-yr-old patients in the diabetes incidence study in Sweden
- 1992
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 41:8, s. 1022-1027
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Tidskriftsartikel (refereegranskat)abstract
- The effect of age on ICA and thyrogastric antibodies at diagnosis of IDDM was evaluated in 633 consecutively diagnosed Swedish diabetic patients aged 15-34 yr and in 282 volunteers of the same age. ICAs were present in 61% (383 of 633) of the patients and in 2% (5 of 282) of control subjects. When the initial classification was considered, ICAs were detected in 69% (327 of 473) of patients with IDDM, 23% (19 of 83) of those with NIDDM, 50% (36 of 72) of those with unclassifiable diabetes, and 20% (1 of 5) of those with secondary diabetes. The frequency of ICA fell significantly (P < 0.001) with age in IDDM patients from 77% (104/135) in those 15-19 yr old to 52% (50 of 96) in 30- to 34-yr-old IDDM patients. The low frequency of ICA in 30- to 34-yr-old IDDM patients was confined to men (42%, 28 of 66). The frequency of gastric (H+, K+-ATPase) antibodies was significantly (P < 0.05) higher in IDDM patients (10%, 47 of 449) than in patients with NIDDM (3%, 3 of 80) and unclassifiable diabetes (4%, 3 of 72). In conclusion, the frequency of ICA at the diagnosis of IDDM in young adult subjects decreases with increasing age, particularly in men. The frequent finding of ICA in patients considered to have NIDDM or unclassifiable diabetes indicates that misclassification of diabetes is frequent in young adult patients recently diagnosed with diabetes.
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- Maklakov, A A, et al.
(författare)
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Adaptive male effects on female ageing in seed beetles
- 2005
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 272:1580, s. 2485-2489
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Tidskriftsartikel (refereegranskat)abstract
- Selection can favour the evolution of a high reproductive rate early in life even when this results in a subsequent increase in the rate of mortality, because selection is relatively weak late in life. However, the optimal reproductive schedule of a female may be suboptimal to any one of her mates, and males may thus be selected to modulate female reproductive rate. Owing to such sexual conflict, coevolution between males and females may contribute to the evolution of senescence. By using replicated beetle populations selected for reproduction at an early or late age, we show that males evolve to affect senescence in females in a manner consistent with the genetic interests of males. ‘Late’ males evolved to decelerate senescence and increase the lifespan of control females, relative to ‘early’ males. Our findings demonstrate that adaptive evolution in one sex may involve its effects on senescence in the other, showing that the evolution of optimal life histories in one sex may be either facilitated or constrained by genes expressed in the other.
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| 10. |
- Ostman, J., et al.
(författare)
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Gender differences and temporal variation in the incidence of type 1 diabetes : results of 8012 cases in the nationwide Diabetes Incidence Study in Sweden 1983-2002
- 2008
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 263:4, s. 386-394
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To establish the gender difference amongst newly diagnosed type 1 diabetic patients aged 15-34 years, considering age at diagnosis, temporal trend and seasonal variation at time of diagnosis. Study design. A population-based prospective study with a mean annual population at risk of 2.3 million. Setting. All departments of medicine, endocrinology and paediatrics and primary health care units in Sweden. Subjects. Incident cases of diabetes aged 15-34 years at diagnosis 1983-2002. Measure instrument. Basic characteristics of patients at diagnosis were reported by the diagnosing doctor on a standardized form. Level of ascertainment was estimated at 80-90%. Results. Amongst all incident cases (n = 8012), 74% was diagnosed with type 1 diabetes. The mean annual incidence rate of type 1 diabetes was 12.7/100 000, in men 16.4/100 000 and in women 8.9/100 000. The incidence of type 1 diabetes decreased slowly by increasing age but was in all age groups higher in men, yielding an overall male/female ratio of 1.8. In both genders the incidence of type 1 diabetes decreased in average of 1.0% per year. A seasonal pattern with significantly higher incidence during January-March and lower during May-July was seen in both genders. Conclusions. A clear male predominance of type 1 diabetes was seen in all ages. The temporal trend and the seasonal pattern was similar in men and women. Hence, internal factors related to the gender rather than differences in the exposure to environmental factors seem to explain the consistent male-female bias in the postpubertal risk of developing type 1 diabetes.
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