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- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 4. |
- Khan, N. K., et al.
(author)
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Prevalence of ECG abnormalities in an international survey of patients with suspected or confirmed heart failure at death or discharge
- 2007
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In: European journal of heart failure. - : Wiley. - 1388-9842. ; 9:5, s. 491-501
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Journal article (peer-reviewed)abstract
- BACKGROUND: Most patients suspected of having heart failure (HF) will get a 12-lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its management has rarely been investigated. METHODS: The EuroHeart Failure survey identified 11,327 patients hospitalised with a suspected diagnosis of HF from 115 hospitals in 24 countries. ECGs were obtained from 9315 patients, of whom 5934 had cardiac imaging tests. The utility of the ECG was assessed for excluding or diagnosing major structural heart disease (MSHD) or major left ventricular systolic dysfunction (MLVSD) and for therapeutic decision making. FINDINGS: MSHD was present in 70% and MLVSD in 54% of patients overall but in only 21% and 5%, respectively, if the ECG was entirely normal. However, <2% of patients had a normal ECG. No single ECG characteristic identified a probability <25% of MSHD or <20% of MLVSD. Patients with QRS width >/=120 ms or anterior pathological Q-waves had a probability >80% of MSHD and >70% of MLVSD. Diagnostic models suggested that electrocardiographic criteria alone were not accurate for the diagnosis or exclusion of important heart disease in this population. However, 2468 patients (42%) had an electrocardiographic finding that should be used to guide the choice of therapy. CONCLUSIONS: A normal ECG is rare in patients with suspected HF but has limited diagnostic value in this setting. The ECG has an important role in guiding therapy.
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| 5. |
- Lindblad-Toh, Kerstin, et al.
(author)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Journal article (peer-reviewed)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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| 6. |
- Lainscak, M., et al.
(author)
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Nonpharmacologic measures and drug compliance in patients with heart failure: data from the EuroHeart Failure Survey
- 2007
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In: The American journal of cardiology. - : Elsevier BV. - 0002-9149. ; 99:6B
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Journal article (peer-reviewed)abstract
- Advice on lifestyle, diet, vaccination, and therapy are part of the standard management of heart failure (HF). However, there is little information on whether patients with HF recall receiving such recommendations and, if so, whether they report following them. We obtained information on the recall of and adherence to nonpharmacologic advice from patients enrolled in the EuroHeart Failure Survey. This article focuses on 2,331 patients who had a clinical diagnosis of HF during the index admission and attended an interview 12 weeks after discharge. Their mean age was 67 +/- 12 years and 38% were women. Patients recalled receiving 4.1 +/- 2.7 items of advice with higher rates in Central Europe and the Mediterranean region. Recall of dietary advice (cholesterol or fat intake, 63%; dietary salt, 60%) was higher than for some other interventions (influenza vaccination, 36%; avoidance of nonsteroidal anti-inflammatory drugs, 17%). Among those who recalled the advice, a substantial proportion indicated that they did not follow advice completely (cholesterol and fat intake, 61%; dietary salt, 63%; influenza vaccination, 75%; avoidance of nonsteroidal anti-inflammatory drugs, 80%), although few patients indicated they ignored the advice completely. Patients who recalled >4 items versus < or =4 items of advice were younger and more often received angiotensin-converting enzyme inhibitors (71% vs 62%), beta-blockers (51% vs 38%), and spironolactone (25% vs 21%). In conclusion, after hospitalization for HF, many patients do not recall nonpharmacologic advice. In addition, a substantial proportion of those who recall the advice follow it incompletely. Younger age and prescription of appropriate pharmacologic treatment are associated with higher rates of recall and implementation.
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| 7. |
- Cox, Angela, et al.
(author)
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A common coding variant in CASP8 is associated with breast cancer risk
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 352-358
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Journal article (peer-reviewed)abstract
- The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
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| 8. |
- Garcia-Closas, Montserrat, et al.
(author)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Journal article (peer-reviewed)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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