| 1. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 3. |
- Haus, Jacob M, et al.
(författare)
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Contractile and connective tissue protein content of human skeletal muscle: : effects of 35 and 90 days of simulated microgravity and exercise countermeasures.
- 2007
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 293:4, s. 1722-1727
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Tidskriftsartikel (refereegranskat)abstract
- We examined the effects of 35 and 90 days of simulated microgravity with or without resistance-exercise (RE) countermeasures on the content of the general skeletal muscle protein fractions (mixed, sarcoplasmic, and myofibrillar) and specific proteins that are critical for muscle function (myosin, actin, and collagen). Subjects from two studies, using either unilateral lower limb suspension (ULLS) or bed rest (BR), comprised four separate groups: 35 days ULLS (n =11), 35 days ULLS+RE (n = 10), 90 days BR (n = 9), and 90 days BR+RE (n = 8). RE consisted of four sets of seven maximal concentric and eccentric repetitions of the quadriceps femoris muscles that were performed 2 or 3 times per week. Pre- and post-simulated weightlessness muscle biopsies were analyzed from the vastus lateralis of all groups and the soleus of the 35-day ULLS and 90-day BR groups. The general protein fractions and the specific proteins myosin, actin, and collagen of the vastus lateralis were unchanged (P > 0.05) in both control and countermeasures groups over 35 and 90 days, despite large changes in quadriceps femoris muscle volume (35 days ULLS: -9%, 35 days ULLS+RE: +8%; and 90 days BR: -18%, 90 days BR+RE: -1%). The soleus demonstrated a decrease in mixed (35 days ULLS: -12%, P = 0.0001; 90 days BR: -12%, P = 0.004) and myofibrillar (35 days ULLS: -12%, P = 0.009; 90 days BR: -8%, P = 0.04) protein, along with large changes in triceps surae muscle volume (35 days ULLS: -11%; 90 days BR: -29%). Despite the loss of quadriceps femoris muscle volume or preservation with RE countermeasures during simulated microgravity, the quadriceps femoris muscles are able to maintain the concentrations of the general protein pools and the main contractile and connective tissue elements. Soleus muscle protein composition appears to be disproportionately altered during long-duration simulated weightlessness.
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| 4. |
- 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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| 5. |
- Bidartondo, Martin, et al.
(författare)
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Preserving accuracy in GenBank
- 2008
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Ingår i: Science. ; 319:5870
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Erlich, Henry, et al.
(författare)
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HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: Analysis of the Type 1 Diabetes Genetics Consortium families
- 2008
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 57:4, s. 1084-1092
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-The Type 1 Diabetes Genetics Consortium has collected type 1 diabetic families worldwide for genetic analysis. The major genetic determinants of type 1 diabetes are alleles at the HLA-DRB1 and DQB1 loci, with both susceptible and protective DR-DQ haplotypes present in all human populations. The aim of this study is to estimate the risk conferred by specific DR-DQ haplotypes and genotypes. RESEARCH DESIGN AND METHODS:-Six hundred and seven Caucasian families and 38 Asian families were typed at high resolution for the DRB1, DQA1, and DQB1 loci. The association analysis was performed by comparing the frequency of DR-DQ haplotypes among the chromosomes transmitted to an affected child with the frequency of chromosomes not transmitted to any affected child. RESULTS-A number of susceptible, neutral, and protective DR-DQ haplotypes have been identified, and a statistically significant hierarchy of type 1 diabetes risk has been established. The most susceptible haplotypes are the DRB1*0301-DQA1*0501-DQB1*0201 (odds ratio [OR] 3.64) and the DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB*0302, and DRB1*0402-DQA1*0301-DQB1*0302 haplotypes (ORs 11.37, 8.39, and 3.63), followed by the DRB1*0404-DQA1*0301-DQB1*0302 (OR 1.59) and the DRB1*0801-DQB1*0401-DQB1*0402 (OR 1.25) haplotypes. The most protective haplotypes are DRB1*1501-DQA1*0102-DQB1*0602 (OR 0.03), DRB1*1401-DQA1*0101-DQB1*0503 (OR 0.02), and DRB1*0701-DQA1*0201-DQB1*0303 (OR 0.02). CONCLUSIONS-Specific combinations of alleles at the DRB1, DQA1, and DQB1 loci determine the extent of haplotypic risk. The comparison of closely related DR-DQ haplotype pairs with different type I diabetes risks allowed identification of specific amino acid positions critical in determining disease susceptibility. These data also indicate that the risk associated with specific HLA haplotypes can be influenced by the genotype context and that the trans-complementing heterodimer encoded by DQA1*0501 and DQB1*0302 confers very high risk.
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