当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas.

Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas.

Abstract：

:Clear-cut inherited Mendelian traits, such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, account for <4% of colorectal cancers. Another 20% of all colorectal cancers are thought to occur in individuals with a significant inherited multifactorial susceptibility to colorectal cancer that is not obviously familial. Incompletely penetrant, comparatively rare missense variants in the adenomatous polyposis coli gene, which is responsible for familial adenomatous polyposis, have been described in patients with multiple colorectal adenomas. These variants represent a category of variation that has been suggested, quite generally, to account for a substantial fraction of such multifactorial inherited susceptibility. The aim of this study was to explore this rare variant hypothesis for multifactorial inheritance by using multiple colorectal adenomas as the model. Patients with multiple adenomas were screened for germ-line variants in a panel of candidate genes. Germ-line DNA was obtained from 124 patients with between 3 and 100 histologically proven synchronous or metachronous adenomatous polyps. All patients were tested for the adenomatous polyposis coli variants I1307K and E1317Q, and variants were also sought in AXIN1 (axin), CTNNB1 (beta-catenin), and the mismatch repair genes hMLH1 and hMSH2. The control group consisted of 483 random controls. Thirty of 124 (24.9%) patients carried potentially pathogenic germ-line variants as compared with 55 ( approximately 12%) of the controls. This overall difference is highly significant, suggesting that many rare variants collectively contribute to the inherited susceptibility to colorectal adenomas.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Fearnhead NS,Wilding JL,Winney B,Tonks S,Bartlett S,Bicknell DC,Tomlinson IP,Mortensen NJ,Bodmer WF

doi

10.1073/pnas.0407187101

keywords:

subject

Has Abstract

pub_date

2004-11-09 00:00:00

pages

15992-7

issue

45

eissn

0027-8424

issn

1091-6490

pii

0407187101

journal_volume

101

pub_type

杂志文章

相关文献

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA文献大全
  • Purification and characterization of the DNA polymerase of human breast cancer particles.

    abstract：:Previous studies have identified human breast tumor particles possessing many of the features characteristic of RNA tumor viruses. In addition to the expected size (600 S) and density (1.16 g/ml) these include possession of an outer membrane and an inner one surrounding a "core" containing a DNA polymerase and a large...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.74.2.764

    authors： Ohno T,Sweet RW,Dejak D,Spiegelman S

    更新日期：1977-02-01 00:00:00

  • CYCLOPS reveals human transcriptional rhythms in health and disease.

    abstract：:Circadian rhythms modulate many aspects of physiology. Knowledge of the molecular basis of these rhythms has exploded in the last 20 years. However, most of these data are from model organisms, and translation to clinical practice has been limited. Here, we present an approach to identify molecular rhythms in humans f...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1619320114

    authors： Anafi RC,Francey LJ,Hogenesch JB,Kim J

    更新日期：2017-05-16 00:00:00

  • Rate enhancement of reconstitution of glyceraldehyde-3-phosphate dehydrogenase by a covalently bound coenzyme analog.

    abstract：:Kinetic analysis of the in vitro reconstitution of glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] from yeast showed that both oxidized and reduced coenzyme enhance the transconformation reaction, which is rate limiting in the sequential foldin...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.77.4.1966

    authors： Jaenicke R,Krebs H,Rudolph R,Woenckhaus C

    更新日期：1980-04-01 00:00:00

  • Interferon induction of IFITM proteins promotes infection by human coronavirus OC43.

    abstract：:IFNs are a family of cytokines that are essential for the antiviral response in vertebrates. Not surprisingly, viruses have adapted to encode virulence factors to cope with the IFN response. Intriguingly, we show here that all three types of interferons, IFN-α, IFN-γ, and IFN-λ, efficiently promote infection by a huma...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1320856111

    authors： Zhao X,Guo F,Liu F,Cuconati A,Chang J,Block TM,Guo JT

    更新日期：2014-05-06 00:00:00

  • Monoclonal antibodies distinguish subtypes of retinal horizontal cells.

    abstract：:Sixteen hybridomas have been identified that secrete antibodies specific to horizontal cells in the carp retina. The hybridomas have been classified into three groups based on their antibody staining patterns: group I, staining associated with all horizontal cells; group II, staining associated with the most abundant ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.81.19.6255

    authors： Young LH,Dowling JE

    更新日期：1984-10-01 00:00:00

  • The animal model of human amnesia: long-term memory impaired and short-term memory intact.

    abstract：:Normal monkeys and monkeys with lesions of the hippocampal formation and adjacent cortex (the H+ lesion) were trained on the delayed nonmatching to sample (DNMS) task with a delay of 0.5 s between the sample and the choice. The animals with H+ lesions learned the task normally at this short delay and also exhibited th...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.91.12.5637

    authors： Alvarez P,Zola-Morgan S,Squire LR

    更新日期：1994-06-07 00:00:00

  • Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa.

    abstract：:Opportunistic infections are often polymicrobial. Two of the most important bacterial opportunistic pathogens of humans, Pseudomonas aeruginosa and Staphylococcus aureus, frequently are coisolated from infections of catheters, endotracheal tubes, skin, eyes, and the respiratory tract, including the airways of people w...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0606756104

    authors： Hoffman LR,Déziel E,D'Argenio DA,Lépine F,Emerson J,McNamara S,Gibson RL,Ramsey BW,Miller SI

    更新日期：2006-12-26 00:00:00

  • Tropical birds have a slow pace of life.

    abstract：:Tropical birds are relatively long-lived and produce few offspring, which develop slowly and mature relatively late in life, the slow end of the life-history axis, whereas temperate birds lie at the opposite end of this continuum. We tested the hypothesis that tropical birds have evolved a reduced basal metabolic rate...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0702212104

    authors： Wiersma P,Muñoz-Garcia A,Walker A,Williams JB

    更新日期：2007-05-29 00:00:00

  • Protein folding under confinement: a role for solvent.

    abstract：:Although most experimental and theoretical studies of protein folding involve proteins in vitro, the effects of spatial confinement may complicate protein folding in vivo. In this study, we examine the folding dynamics of villin (a small fast folding protein) with explicit solvent confined to an inert nanopore. We hav...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0608256104

    authors： Lucent D,Vishal V,Pande VS

    更新日期：2007-06-19 00:00:00

  • B850 pigment-protein complex of Rhodopseudomonas sphaeroides: Extinction coefficients, circular dichroism, and the reversible binding of bacteriochlorophyll.

    abstract：:Chromatophores of Rhodopseudomonas sphaeroides yield the antenna complex B850 in either of two states, depending on the method of isolation. Methods using dodecyl (= lauryl) dimethylamine oxide yield B850 with an absorption spectrum like that in vivo: the bands at 800 and 850 nm, due to the bacteriochlorophyll (Bchl) ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.78.9.5583

    authors： Clayton RK,Clayton BJ

    更新日期：1981-09-01 00:00:00

  • Maximum leaf conductance driven by CO2 effects on stomatal size and density over geologic time.

    abstract：:Stomatal pores are microscopic structures on the epidermis of leaves formed by 2 specialized guard cells that control the exchange of water vapor and CO(2) between plants and the atmosphere. Stomatal size (S) and density (D) determine maximum leaf diffusive (stomatal) conductance of CO(2) (g(c(max))) to sites of assim...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0904209106

    authors： Franks PJ,Beerling DJ

    更新日期：2009-06-23 00:00:00

  • Phenotypic integration emerges from aposematism and scale in poison frogs.

    abstract：:Complex phenotypes can be modeled as networks of component traits connected by genetic, developmental, or functional interactions. Aposematism, which has evolved multiple times in poison frogs (Dendrobatidae), links a warning signal to a chemical defense against predators. Other traits are involved in this complex phe...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1010952108

    authors： Santos JC,Cannatella DC

    更新日期：2011-04-12 00:00:00

  • Three types of rescue can avert extinction in a changing environment.

    abstract：:Setting aside high-quality large areas of habitat to protect threatened populations is becoming increasingly difficult as humans fragment and degrade the environment. Biologists and managers therefore must determine the best way to shepherd small populations through the dual challenges of reductions in both the number...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1504732112

    authors： Hufbauer RA,Szűcs M,Kasyon E,Youngberg C,Koontz MJ,Richards C,Tuff T,Melbourne BA

    更新日期：2015-08-18 00:00:00

  • Krüppel-like factor 2 (KLF2) regulates B-cell reactivity, subset differentiation, and trafficking molecule expression.

    abstract：:The transcription factor Krüppel-like factor 2 (KLF2) is critical for normal trafficking of T lymphocytes, but its role in B cells is unclear. We report that B cell-specific KLF2 deficiency leads to decreased expression of the trafficking molecules CD62L and β7-integrin, yet expression of sphingosine-1 phosphate recep...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1013168108

    authors： Hart GT,Wang X,Hogquist KA,Jameson SC

    更新日期：2011-01-11 00:00:00

  • Homology of lipoprotein lipase to pancreatic lipase.

    abstract：:Bovine milk lipoprotein lipase was subjected to amino acid sequence analysis. The first 19 amino-terminal residues were Asp-Arg-Ile-Thr-Gly-Gly-Lys-Asp-Phe-Arg-Asp-Ile-Glu-Ser-Lys-Phe-Ala-Leu- Arg. In addition, reversed-phase high-performance liquid chromatography of a tryptic digest of reduced and alkylated lipase re...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.83.12.4185

    authors： Ben-Avram CM,Ben-Zeev O,Lee TD,Haaga K,Shively JE,Goers J,Pedersen ME,Reeve JR Jr,Schotz MC

    更新日期：1986-06-01 00:00:00

  • Mechanism of removal of senescent cells by human macrophages in situ.

    abstract：:Mechanisms by which macrophages discriminate between "mature-self" and "senescent-self" were investigated using the human red blood cell (RBC) system as a model. Conditions simulating those encountered in situ were adhered to as closely as possible by using short term culture techniques and incubating with autologous ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.72.9.3521

    authors： Kay MM

    更新日期：1975-09-01 00:00:00

  • El Nino/Southern Oscillation response to global warming.

    abstract：:The El Niño/Southern Oscillation (ENSO) phenomenon, originating in the Tropical Pacific, is the strongest natural interannual climate signal and has widespread effects on the global climate system and the ecology of the Tropical Pacific. Any strong change in ENSO statistics will therefore have serious climatic and eco...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0710860105

    authors： Latif M,Keenlyside NS

    更新日期：2009-12-08 00:00:00

  • Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells.

    abstract：:We have previously described a gene delivery system based upon the receptor-mediated endocytosis of DNA complexed with transferrin-polycation conjugates. This delivery system has been found to be very effective for both the internalization and the expression of genetic material in cells that have many transferrin rece...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.88.10.4255

    authors： Wagner E,Cotten M,Foisner R,Birnstiel ML

    更新日期：1991-05-15 00:00:00

  • Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants.

    abstract：:Plasma samples exhibiting alloalbuminemia on electrophoresis at pH 8.6 were requested from clinical laboratories throughout Sweden. Nine variants, each representing a different single point mutation, were found in 100 apparently unrelated Swedes. The overall prevalence of alloalbuminemia was estimated at 1:1700. Mutat...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.89.17.8225

    authors： Carlson J,Sakamoto Y,Laurell CB,Madison J,Watkins S,Putnam FW

    更新日期：1992-09-01 00:00:00

  • Influence of chromosomal integration on glucocorticoid-regulated transcription of growth-stimulating papillomavirus genes E6 and E7 in cervical carcinoma cells.

    abstract：:In most cervical carcinoma cells the E6 and E7 genes of specific human papillomaviruses are transcribed from viral sequences integrated into host cell chromosomes. Glucocorticoids activate the promoter elements of various human papillomaviruses in transient-expression assays. We have analyzed the effect of dexamethaso...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.88.4.1411

    authors： von Knebel Doeberitz M,Bauknecht T,Bartsch D,zur Hausen H

    更新日期：1991-02-15 00:00:00

  • Roles of the anaphase-promoting complex/cyclosome and of its activator Cdc20 in functional substrate binding.

    abstract：:The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin-protein ligase that targets for degradation cell-cycle regulatory proteins during exit from mitosis and in the G1 phase of the cell cycle. The activity of APC/C in mitosis and in G1 requires interaction with the activator proteins Cdc20 and C...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0510695103

    authors： Eytan E,Moshe Y,Braunstein I,Hershko A

    更新日期：2006-02-14 00:00:00

  • SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx.

    abstract：:Small ubiquitin-like modifier (SUMO) modification is emerging as an important control in transcription regulation. Here, we show that CREB-binding protein (CBP), a versatile transcriptional coactivator for numerous transcription factors in response to diverse signaling events, can be modified by SUMO-1 at lysine resid...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0504460102

    authors： Kuo HY,Chang CC,Jeng JC,Hu HM,Lin DY,Maul GG,Kwok RP,Shih HM

    更新日期：2005-11-22 00:00:00

  • Refractoriness to melatonin occurs independently at multiple brain sites in Siberian hamsters.

    abstract：:The mid-winter development of refractoriness to melatonin (Mel) triggers recrudescence of the atrophied reproductive apparatus of rodents. As a consequence, over-wintering animals become reproductively competent just before the onset of spring conditions favorable for breeding. The neural target tissues that cease to ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.111140398

    authors： Freeman DA,Zucker I

    更新日期：2001-05-22 00:00:00

  • Biologic and antigenic similarity of virus-induced migration inhibition factor to conventional, lymphocyte-derived migration inhibition factor.

    abstract：:Macrophage migration inhibition factor (MIF) is one of a class of lymphocyte-derived mediator substances (lymphokines) which plays a role in the mechanism of cellular immunity. A variety of other soluble factors produced by non-lymphoid cells have been shown to have effects on macrophage mobility similar to that of MI...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.72.4.1641

    authors： Yoshida T,Bigazzi P,Cohen S

    更新日期：1975-04-01 00:00:00

  • Archaeological and chemical evidence for early salt production in China.

    abstract：:Salt production and trade is thought to be critical to the development of all states and emergent empires. Until now, however, scientific evidence of early salt production has rarely been presented, and no studies of early Chinese salt production have provided unequivocal proof. Here, we report x-ray fluorescence, x-r...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0502985102

    authors： Flad R,Zhu J,Wang C,Chen P,von Falkenhausen L,Sun Z,Li S

    更新日期：2005-08-30 00:00:00

  • Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties.

    abstract：:Phase separation of multivalent protein and RNA molecules underlies the biogenesis of biomolecular condensates such as membraneless organelles. In vivo, these condensates encompass hundreds of distinct types of molecules that typically organize into multilayered structures supporting the differential partitioning of m...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1821038116

    authors： Boeynaems S,Holehouse AS,Weinhardt V,Kovacs D,Van Lindt J,Larabell C,Van Den Bosch L,Das R,Tompa PS,Pappu RV,Gitler AD

    更新日期：2019-04-16 00:00:00

  • Global human mandibular variation reflects differences in agricultural and hunter-gatherer subsistence strategies.

    abstract：:Variation in the masticatory behavior of hunter-gatherer and agricultural populations is hypothesized to be one of the major forces affecting the form of the human mandible. However, this has yet to be analyzed at a global level. Here, the relationship between global mandibular shape variation and subsistence economy ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1113050108

    authors： von Cramon-Taubadel N

    更新日期：2011-12-06 00:00:00

  • Amplification and deregulation of MYC following Epstein-Barr virus infection of a human B-cell line.

    abstract：:In Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) the role of EBV in the translocation and deregulation of the MYC oncogene remains unknown. By utilizing an EBV-negative BL (BJAB) and several EBV-positive sublines derived from it by in vitro infection, it was possible to show that the presence of the virus wa...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.84.16.5838

    authors： Lacy J,Summers WP,Watson M,Glazer PM,Summers WC

    更新日期：1987-08-01 00:00:00

  • The Arabidopsis SUMO E3 ligase SIZ1 controls phosphate deficiency responses.

    abstract：:Plants sense phosphate (Pi) deficiency and initiate signaling that controls adaptive responses necessary for Pi acquisition. Herein, evidence establishes that AtSIZ1 is a plant small ubiquitin-like modifier (SUMO) E3 ligase and is a focal controller of Pi starvation-dependent responses. T-DNA insertional mutated allel...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0500778102

    authors： Miura K,Rus A,Sharkhuu A,Yokoi S,Karthikeyan AS,Raghothama KG,Baek D,Koo YD,Jin JB,Bressan RA,Yun DJ,Hasegawa PM

    更新日期：2005-05-24 00:00:00

  • Possible ideal lac operator: Escherichia coli lac operator-like sequences from eukaryotic genomes lack the central G X C pair.

    abstract：:Five DNA fragments have been cloned from yeast, chicken, and mouse DNA that titrate lac repressor in an Escherichia coli lac+ I+Z+ wild-type strain when on a multi-copy plasmid. The five repressor-binding sequences have been identified by DNA sequence determinations and DNase cleavage-inhibition patterns. They share t...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.81.6.1624

    authors： Simons A,Tils D,von Wilcken-Bergmann B,Müller-Hill B

    更新日期：1984-03-01 00:00:00