Identifying autism loci and genes by tracing recent shared ancestry   总被引：2，自引：0，他引：2  

Morrow EM  Yoo SY  Flavell SW  Kim TK  Lin Y  Hill RS  Mukaddes NM  Balkhy S  Gascon G  Hashmi A  Al-Saad S  Ware J  Joseph RM  Greenblatt R  Gleason D  Ertelt JA  Apse KA  Bodell A  Partlow JN  Barry B  Yao H  Markianos K  Ferland RJ  Greenberg ME  Walsh CA 《Science (New York, N.Y.)》2008,321(5886):218-223

To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of "homozygosity mapping" in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations.  相似文献   

Medicine. The future of personal genomics     

McGuire AL  Cho MK  McGuire SE  Caulfield T 《Science (New York, N.Y.)》2007,317(5845):1687

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Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast     

Roguev A  Bandyopadhyay S  Zofall M  Zhang K  Fischer T  Collins SR  Qu H  Shales M  Park HO  Hayles J  Hoe KL  Kim DU  Ideker T  Grewal SI  Weissman JS  Krogan NJ 《Science (New York, N.Y.)》2008,322(5900):405-410

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Direct measurement of the reaction front in chemically amplified photoresists     

Lin EK  Soles CL  Goldfarb DL  Trinque BC  Burns SD  Jones RL  Lenhart JL  Angelopoulos M  Willson CG  Satija SK  Wu WL 《Science (New York, N.Y.)》2002,297(5580):372-375

The continuing drive by the semiconductor industry to fabricate smaller structures using photolithography will soon require dimensional control at length scales comparable to the size of the polymeric molecules in the materials used to pattern them. The current technology, chemically amplified photoresists, uses a complex reaction-diffusion process to delineate patterned areas with high spatial resolution. However, nanometer-level control of this critical process is limited by the lack of direct measurements of the reaction front. We demonstrate the use of x-ray and neutron reflectometry as a general method to measure the spatial evolution of the reaction-diffusion process with nanometer resolution. Measuring compositional profiles, provided by deuterium-labeled reactant groups for neutron scattering contrast, we show that the reaction front within the material is broad rather than sharply defined and the compositional profile is altered during development. Measuring the density profile, we directly correlate the developed film structure with that of the reaction front.  相似文献   

Crystal structure of a self-spliced group II intron     

Toor N  Keating KS  Taylor SD  Pyle AM 《Science (New York, N.Y.)》2008,320(5872):77-82

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Radioactive elements on Mercury's surface from MESSENGER: implications for the planet's formation and evolution     

Peplowski PN  Evans LG  Hauck SA  McCoy TJ  Boynton WV  Gillis-Davis JJ  Ebel DS  Goldsten JO  Hamara DK  Lawrence DJ  McNutt RL  Nittler LR  Solomon SC  Rhodes EA  Sprague AL  Starr RD  Stockstill-Cahill KR 《Science (New York, N.Y.)》2011,333(6051):1850-1852

The MESSENGER Gamma-Ray Spectrometer measured the average surface abundances of the radioactive elements potassium (K, 1150 ± 220 parts per million), thorium (Th, 220 ± 60 parts per billion), and uranium (U, 90 ± 20 parts per billion) in Mercury's northern hemisphere. The abundance of the moderately volatile element K, relative to Th and U, is inconsistent with physical models for the formation of Mercury requiring extreme heating of the planet or its precursor materials, and supports formation from volatile-containing material comparable to chondritic meteorites. Abundances of K, Th, and U indicate that internal heat production has declined substantially since Mercury's formation, consistent with widespread volcanism shortly after the end of late heavy bombardment 3.8 billion years ago and limited, isolated volcanic activity since.  相似文献   

Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum     

Bendall SC  Simonds EF  Qiu P  Amir el-AD  Krutzik PO  Finck R  Bruggner RV  Melamed R  Trejo A  Ornatsky OI  Balderas RS  Plevritis SK  Sachs K  Pe'er D  Tanner SD  Nolan GP 《Science (New York, N.Y.)》2011,332(6030):687-696

Flow cytometry is an essential tool for dissecting the functional complexity of hematopoiesis. We used single-cell "mass cytometry" to examine healthy human bone marrow, measuring 34 parameters simultaneously in single cells (binding of 31 antibodies, viability, DNA content, and relative cell size). The signaling behavior of cell subsets spanning a defined hematopoietic hierarchy was monitored with 18 simultaneous markers of functional signaling states perturbed by a set of ex vivo stimuli and inhibitors. The data set allowed for an algorithmically driven assembly of related cell types defined by surface antigen expression, providing a superimposable map of cell signaling responses in combination with drug inhibition. Visualized in this manner, the analysis revealed previously unappreciated instances of both precise signaling responses that were bounded within conventionally defined cell subsets and more continuous phosphorylation responses that crossed cell population boundaries in unexpected manners yet tracked closely with cellular phenotype. Collectively, such single-cell analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention.  相似文献   

Discovery of a viral NLR homolog that inhibits the inflammasome     

Gregory SM  Davis BK  West JA  Taxman DJ  Matsuzawa S  Reed JC  Ting JP  Damania B 《Science (New York, N.Y.)》2011,331(6015):330-334

The NLR (nucleotide binding and oligomerization, leucine-rich repeat) family of proteins senses microbial infections and activates the inflammasome, a multiprotein complex that promotes microbial clearance. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to several human malignancies. We found that KSHV Orf63 is a viral homolog of human NLRP1. Orf63 blocked NLRP1-dependent innate immune responses, including caspase-1 activation and processing of interleukins IL-1β and IL-18. KSHV Orf63 interacted with NLRP1, NLRP3, and NOD2. Inhibition of Orf63 expression resulted in increased expression of IL-1β during the KSHV life cycle. Furthermore, inhibition of NLRP1 was necessary for efficient reactivation and generation of progeny virus. The viral homolog subverts the function of cellular NLRs, which suggests that modulation of NLR-mediated innate immunity is important for the lifelong persistence of herpesviruses.  相似文献   

A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome   总被引：6，自引：0，他引：6  

Sultan M  Schulz MH  Richard H  Magen A  Klingenhoff A  Scherf M  Seifert M  Borodina T  Soldatov A  Parkhomchuk D  Schmidt D  O'Keeffe S  Haas S  Vingron M  Lehrach H  Yaspo ML 《Science (New York, N.Y.)》2008,321(5891):956-960

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Genome sequence of the PCE-dechlorinating bacterium Dehalococcoides ethenogenes     

Seshadri R  Adrian L  Fouts DE  Eisen JA  Phillippy AM  Methe BA  Ward NL  Nelson WC  Deboy RT  Khouri HM  Kolonay JF  Dodson RJ  Daugherty SC  Brinkac LM  Sullivan SA  Madupu R  Nelson KE  Kang KH  Impraim M  Tran K  Robinson JM  Forberger HA  Fraser CM  Zinder SH  Heidelberg JF 《Science (New York, N.Y.)》2005,307(5706):105-108

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