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991.
Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland 总被引:1,自引:0,他引:1
McGinnis RE Fox H Yates P Cameron LA Barnes MR Gray IC Spurr NK Hurko O St Clair D 《Nature genetics》2001,28(2):128-129
The NOTCH4 gene was recently reported to be associated with schizophrenia based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls. 相似文献
992.
993.
A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy 总被引:20,自引:0,他引:20
Zhang K Kniazeva M Han M Li W Yu Z Yang Z Li Y Metzker ML Allikmets R Zack DJ Kakuk LE Lagali PS Wong PW MacDonald IM Sieving PA Figueroa DJ Austin CP Gould RJ Ayyagari R Petrukhin K 《Nature genetics》2001,27(1):89-93
Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration. 相似文献
994.
High-resolution haplotype structure in the human genome 总被引:41,自引:0,他引:41
Linkage disequilibrium (LD) analysis is traditionally based on individual genetic markers and often yields an erratic, non-monotonic picture, because the power to detect allelic associations depends on specific properties of each marker, such as frequency and population history. Ideally, LD analysis should be based directly on the underlying haplotype structure of the human genome, but this structure has remained poorly understood. Here we report a high-resolution analysis of the haplotype structure across 500 kilobases on chromosome 5q31 using 103 single-nucleotide polymorphisms (SNPs) in a European-derived population. The results show a picture of discrete haplotype blocks (of tens to hundreds of kilobases), each with limited diversity punctuated by apparent sites of recombination. In addition, we develop an analytical model for LD mapping based on such haplotype blocks. If our observed structure is general (and published data suggest that it may be), it offers a coherent framework for creating a haplotype map of the human genome. 相似文献
995.
A radiation hybrid map of mouse genes 总被引:13,自引:0,他引:13
Hudson TJ Church DM Greenaway S Nguyen H Cook A Steen RG Van Etten WJ Castle AB Strivens MA Trickett P Heuston C Davison C Southwell A Hardisty R Varela-Carver A Haynes AR Rodriguez-Tome P Doi H Ko MS Pontius J Schriml L Wagner L Maglott D Brown SD Lander ES Schuler G Denny P 《Nature genetics》2001,29(2):201-205
A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome. 相似文献
996.
997.
Marth G Yeh R Minton M Donaldson R Li Q Duan S Davenport R Miller RD Kwok PY 《Nature genetics》2001,27(4):371-372
There is a concerted effort by a number of public and private groups to identify a large set of human single-nucleotide polymorphisms (SNPs). As of March 2001, 2.84 million SNPs have been deposited in the public database, dbSNP, at the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/SNP/). The 2.84 million SNPs can be grouped into 1.65 million non-redundant SNPs. As part of the International SNP Map Working Group, we recently published a high-density SNP map of the human genome consisting of 1.42 million SNPs (ref. 3). In addition, numerous SNPs are maintained in proprietary databases. Our survey of more than 1,200 SNPs indicates that more than 80% of TSC and Washington University candidate SNPs are polymorphic and that approximately 50% of the candidate SNPs from these two sources are common SNPs (with minor allele frequency of > or =20%) in any given population. 相似文献
998.
Grimm DR Colter MB Braunschweig M Alexander LJ Neame PJ Kim HK 《Cellular and molecular life sciences : CMLS》2001,58(1):148-159
Factor V is a plasma protein essential for blood coagulation. This protein is involved in activated protein C resistance,
the most common inherited thrombotic disorder known. We utilized the polymerase chain reaction to clone the porcine factor
V gene by generating overlapping clones amplified with primers chosen by comparison with known nucleotide sequences. The porcine
factor V cDNA contig encodes a predicted 2258-amino acid protein, making it the largest in comparison to the bovine, human,
and murine proteins. Porcine factor V has the highest level of homology with bovine factor V, but also has high levels of
conservation of important residues with all the species. Radiation hybrid mapping assigned the porcine factor V gene to chromosome
4. Three-dimensional models of factor V were generated and used to analyze membrane-binding sites in terms of conserved, and
therefore likely important residues.
Received 3 October 2000; revised 23 November 2000; accepted 6 December 2000 相似文献
999.
Larbalestier DC Cooley LD Rikel MO Polyanskii AA Jiang J Patnaik S Cai XY Feldmann DM Gurevich A Squitieri AA Naus MT Eom CB Hellstrom EE Cava RJ Regan KA Rogado N Hayward MA He T Slusky JS Khalifah P Inumaru K Haas M 《Nature》2001,410(6825):186-189
The discovery of superconductivity at 39 K in magnesium diboride, MgB2, raises many issues, a critical one being whether this material resembles a high-temperature copper oxide superconductor or a low-temperature metallic superconductor in terms of its behaviour in strong magnetic fields. Although the copper oxides exhibit very high transition temperatures, their in-field performance is compromized by their large anisotropy, the result of which is to restrict high bulk current densities to a region much less than the full magnetic-field-temperature (H-T) space over which superconductivity is found. Moreover, the weak coupling across grain boundaries makes transport current densities in untextured polycrystalline samples low and strongly sensitive to magnetic field. Here we report that, despite the multiphase, untextured, microscale, subdivided nature of our MgB2 samples, supercurrents flow throughout the material without exhibiting strong sensitivity to weak magnetic fields. Our combined magnetization, magneto-optical, microscopy and X-ray investigations show that the supercurrent density is mostly determined by flux pinning, rather than by the grain boundary connectivity. Our results therefore suggest that this new superconductor class is not compromized by weak-link problems, a conclusion of significance for practical applications if higher temperature analogues of this compound can be discovered. 相似文献
1000.
The electrical and optical properties of conjugated polymers have received considerable attention in the context of potentially low-cost replacements for conventional metals and inorganic semiconductors. Charge transport in these organic materials has been characterized in both the doped-metallic and the semiconducting state, but superconductivity has not hitherto been observed in these polymers. Here we report a distinct metal-insulator transition and metallic levels of conductivity in a polymer field-effect transistor. The active material is solution-cast regioregular poly(3-hexylthiophene), which forms relatively well ordered films owing to self-organization, and which yields a high charge carrier mobility (0.05-0.1 cm2 V(-1) s(-1)) at room temperature. At temperatures below approximately 2.35 K with sheet carrier densities exceeding 2.5 x 10(14) cm(-2), the polythiophene film becomes superconducting. The appearance of superconductivity seems to be closely related to the self-assembly properties of the polymer, as the introduction of additional disorder is found to suppress superconductivity. Our findings therefore demonstrate the feasibility of tuning the electrical properties of conjugated polymers over the largest range possible-from insulating to superconducting. 相似文献