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- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Eriksson, Jan W., et al.
(författare)
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Insulin sensitivity following treatment with the alpha 1-blocker bunazosin retard and the beta 1-blocker atenolol in hypertensive non-insulin-dependent diabetes mellitus patients
- 1996
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 14:12, s. 1469-1475
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To compare the effects of the alpha 1-blocker bunazosin retard and the beta 1-blocker atenolol (Uniloc) on insulin sensitivity and glucose and lipid homeostasis in patients with type-2 diabetes and hypertension.METHODS:Patients with controlled type-2 diabetes (non-insulin-dependent diabetes mellitus), treated by diet or oral sulphonylurea derivatives, and with mild-to-moderate hypertension were include in a randomized, parallel group, double-blind, multicentre study. After a single-blind placebo run-in period lasting 4-6 weeks, the patients were treated either with bunazosin retard or with atenolol for a further 16 weeks including an initial dose titration period to achieve blood pressure control. Treatment involved 3, 6 or 12 mg bunazosin retard tablets or 25, 50 or 100 mg atenolol tablets, administered orally once a day and prescribed according to blood pressure response. The euglycaemic hyper-insulinaemic clamp technique was used to assess insulin sensitivity both after the placebo period and after the active treatment. A total of 95 patients was enrolled in the study (placebo phase). Forty-eight patients were withdrawn from the placebo phase, mainly due to their blood pressures being outside the required range (seated diastolic blood pressure 90-114 mmHg) and 47 patients were allocated randomly to active treatment. Of these, 23 were administered bunazosin retard and 24 atenolol. All evaluations were on an intention-to-treat basis.RESULTS:Insulin sensitivity assessed as glucose utilization during the clamp was significantly higher following bunazosin retard compared with following atenolol administration (3.52 +/- 0.27 versus 2.86 +/- 0.19 units of metabolic clearance rate of glucose index, P < 0.05). The insulin level attained during clamps (infusion rate 56 mU/m2 per min) was higher (P < 0.05) following atenolol (117 +/- 5 mU/l) than it was following bunazosin retard administration (102 +/- 5) or placebo (108 +/- 3), possibly due to an impaired insulin clearance. Compared with placebo, atenolol treatment resulted in significantly increased glucosylated haemoglobin whereas bunazosin retard had no significant effect. The two drugs did not show any consistent differences in lipid profile or fibrinogen and plasminogen activator inhibitor 1 levels. During the study seven serious adverse events were reported and one was reported shortly after completion of the study. All except one were classified as not related to the study drug and five of them occurred during placebo treatment. The non-serious side effects were in general considered to be either unrelated to the test drugs or expected effects of the two respective drug classes. Both bunazosin retard and atenolol displayed acceptable safety profiles.CONCLUSION:Bunazosin retard treatment in hypertensive non-insulin-dependent diabetes mellitus patients appears to be associated with a slightly higher insulin sensitivity than is atenolol.
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| 7. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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