Research Topics
| LEN ALEXANDER PENNACCHIOSummaryAffiliation: Lawrence Berkeley National Laboratory Country: USA Publications
Research Grants
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Detail Information
Publications
In vivo characterization of human APOA5 haplotypesNadav Ahituv
Genomics Division, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Genomics 90:674-9. 2007....
Enhancers: five essential questionsLen A Pennacchio
Genomics Division, One Cyclotron Road, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Nat Rev Genet 14:288-95. 2013....
The INSIG2 rs7566605 genetic variant does not play a major role in obesity in a sample of 24,722 individuals from four cohortsJan Bressler
Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
BMC Med Genet 10:56. 2009..The combined study sample is comprised of 24,722 white, African-American, and Mexican-American participants...- SNP-VISTA: an interactive SNP visualization toolNameeta Shah
Institute for Data Analysis and Visualization, IDAV, Department of Computer Science, University of California, Davis, One ShieldsAve, Davis, CA 95616, USA
BMC Bioinformatics 6:292. 2005..The program is available at http://genome.lbl.gov/vista/snpvista1... - Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levelsLen A Pennacchio
Genome Sciences Department, MS 84 171, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA
Hum Mol Genet 11:3031-8. 2002..Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population... - In vivo enhancer analysis of human conserved non-coding sequencesLen A Pennacchio
US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA
Nature 444:499-502. 2006.... - Insights from human/mouse genome comparisonsLen A Pennacchio
Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, California, USA
Mamm Genome 14:429-36. 2003..Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis... - Comparative genomic tools and databases: providing insights into the human genomeLen A Pennacchio
Genome Sciences Department, MS 84-171, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA
J Clin Invest 111:1099-106. 2003 - Apolipoprotein A5, a newly identified gene that affects plasma triglyceride levels in humans and miceLen A Pennacchio
Department of Genome Sciences, MS 84 171, One Cyclotron Rd, Lawrence Berkeley National Laboratory, Berkeley, Calif 94720, USA
Arterioscler Thromb Vasc Biol 23:529-34. 2003..In summary, APOA5 represents a newly discovered gene involved in triglyceride metabolism in both humans and mice whose mechanism of action remains to be deciphered... - Comparative genomics: a tool to functionally annotate human DNAJan Fang Cheng
Genomics Division, Lawrence Berkeley National Laboratory, CA, USA
Methods Mol Biol 366:229-51. 2007..These pursuits have led to the development of a variety of valuable databases and resources that should serve as a routine toolbox for biological discovery... - Ultraconservation identifies a small subset of extremely constrained developmental enhancersAxel Visel
Genomics Division, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Nat Genet 40:158-60. 2008..Developmental enhancers were equally prevalent in both populations, suggesting instead that ultraconservation identifies a small, functionally indistinct subset of similarly constrained cis-regulatory elements... - VISTA Enhancer Browser--a database of tissue-specific human enhancersAxel Visel
Genomics Division, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA
Nucleic Acids Res 35:D88-92. 2007..These experimentally validated training sets are expected to provide a basis for a wide range of downstream computational and functional studies of enhancer function... - Analysis of apolipoprotein A5, c3, and plasma triglyceride concentrations in genetically engineered miceNadine Baroukh
Department of Genome Sciences, Lawrence Berkeley National Laboratory, Berkeley, Calif 94720, USA
Arterioscler Thromb Vasc Biol 24:1297-302. 2004..In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. These similar findings raised the issue of the relationship between these 2 genes and altered triglycerides... - Close sequence comparisons are sufficient to identify human cis-regulatory elementsShyam Prabhakar
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Genome Res 16:855-63. 2006..Lastly, we determined that, in addition to strength of conservation, genomic location and/or density of surrounding conserved elements must also be considered in selecting candidate enhancers for in vivo testing at embryonic time points... - The amphioxus genome and the evolution of the chordate karyotypeNicholas H Putnam
Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA
Nature 453:1064-71. 2008..These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution... - Human-specific gain of function in a developmental enhancerShyam Prabhakar
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Science 321:1346-50. 2008.... - ChIP-Seq identification of weakly conserved heart enhancersMatthew J Blow
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
Nat Genet 42:806-10. 2010..These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary conservation of embryonic enhancers can vary depending on tissue type... - Comparative and functional analysis of cardiovascular-related genesJan Fang Cheng
Department of Genome Sciences, MS 84 171, One Cyclotron Road, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Pharmacogenomics 4:571-82. 2003..These data have provided a glimpse into the variety of possible insights from deep vertebrate sequence comparisons and the identification of putative gene regulatory elements... - Phylo-VISTA: interactive visualization of multiple DNA sequence alignmentsNameeta Shah
Center for Image Processing and Integrated Computing, Department of Computer Science, One Shields Avenue, University of California, Davis, CA 95616 8562, USA
Bioinformatics 20:636-43. 2004..To be efficient these visualization algorithms must support the ability to accommodate consistently a wide range of evolutionary distances in a comparison framework based upon phylogenetic relationships... - Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboonsQian-fei Wang
Genome Sciences Department, Lawrence Berkeley National Laboratory, CA 94720, USA
Hum Mol Genet 13:1049-56. 2004.... - In vivo characterization of a vertebrate ultraconserved enhancerFrancis Poulin
Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA
Genomics 85:774-81. 2005.... - Predicting tissue-specific enhancers in the human genomeLen A Pennacchio
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Genome Res 17:201-11. 2007..These results indicate the power of combining complementary genomic data sets as an initial computational foray into a global view of tissue-specific gene regulation in vertebrates... - Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceride-rich lipoproteins and removal of their remnantsItamar Grosskopf
Department of Medicine, School of Medicine, Stanford University, California, USA
Arterioscler Thromb Vasc Biol 25:2573-9. 2005..ApoAV, a newly discovered apoprotein, affects plasma triglyceride level. To determine how this occurs, we studied triglyceride-rich lipoprotein (TRL) metabolism in mice deficient in apoAV... - Genomic views of distant-acting enhancersAxel Visel
Genomics Division, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Nature 461:199-205. 2009..Genome-wide approaches to their discovery and functional characterization are now available and provide a growing knowledge base for the systematic exploration of their role in human biology and disease susceptibility... - A PYY Q62P variant linked to human obesityNadav Ahituv
Genomics Division, One Cyclotron Road, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Hum Mol Genet 15:387-91. 2006..Taken together, these results are the first to support that rare sequence variants within PYY can influence human susceptibility to obesity... - Comparative genomic analysis as a tool for biological discoveryMarcelo A Nobrega
Genome Sciences Department, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA
J Physiol 554:31-9. 2004..We also discuss emerging concepts as this field matures, such as how to properly select which species for comparison, which may differ significantly between independent studies... - Comparative genomic analysis reveals a distant liver enhancer upstream of the COUP-TFII geneNadine Baroukh
Genomics Division, Lawrence Berkeley National Laboratory, MS 84-171, One Cyclotron Road, Berkeley, California 94720, USA
Mamm Genome 16:91-5. 2005.... - The sequence and analysis of duplication-rich human chromosome 16Joel Martin
DOE Joint Genome Institute, 2800 Mitchell Avenue, Walnut Creek, California 94598, USA
Nature 432:988-94. 2004.... - Enhancer identification through comparative genomicsAxel Visel
Genomics Division, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Semin Cell Dev Biol 18:140-52. 2007..It is anticipated that cardiac-related genes and the identification of their distant-acting transcriptional enhancers are particularly poised to benefit from these modern capabilities... - Deletion of ultraconserved elements yields viable miceNadav Ahituv
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America
PLoS Biol 5:e234. 2007..These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability... - Functional autonomy of distant-acting human enhancersAxel Visel
Genomics Division, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA
Genomics 93:509-13. 2009..These data indicate that human developmental enhancers are highly modular and functionally autonomous and suggest that genomic enhancer shuffling may have contributed to the evolution of complex gene expression patterns in vertebrates... - Medical sequencing at the extremes of human body massNadav Ahituv
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Am J Hum Genet 80:779-91. 2007..Together, these data suggest that multiple rare alleles contribute to obesity in the population and provide a medical sequencing-based approach to detect them... - ChIP-seq accurately predicts tissue-specific activity of enhancersAxel Visel
Genomics Division, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Nature 457:854-8. 2009.... - Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in miceAxel Visel
Genomics Division, MS 84 171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Nature 464:409-12. 2010.... - Lack of support for the association between GAD2 polymorphisms and severe human obesityMichael M Swarbrick
Diabetes Center, University of California, San Francisco, California, USA
PLoS Biol 3:e315. 2005.... - Lack of MEF2A mutations in coronary artery diseaseLi Weng
US Department of Energy, Joint Genome Institute, Walnut Creek, California, USA
J Clin Invest 115:1016-20. 2005..These studies support that MEF2A mutations are not a common cause of CAD in white people and argue strongly against a role for the MEF2A 21-bp deletion in autosomal dominant CAD... - Apolipoprotein AIV gene variant S347 is associated with increased risk of coronary heart disease and lower plasma apolipoprotein AIV levelsWai Man R Wong
Division of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Royal Free and University College Medical School, London, UK
Circ Res 92:969-75. 2003..90+/-0.12 mg/dL) (P=0.035). These results demonstrate that genetic variation in and around APOA4, independent of the effects of triglyceride, is associated with risk of CHD and apoAIV levels, supporting an antiatherogenic role for apoAIV... - Linkage and association between distinct variants of the APOA1/C3/A4/A5 gene cluster and familial combined hyperlipidemiaSophie Eichenbaum-Voline
Genomic and Molecular Medicine Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UK
Arterioscler Thromb Vasc Biol 24:167-74. 2004..CONCLUSIONS: A combined linkage and association analysis establishes that variation at the APOA1/C3/A4/A5 gene cluster contributes to FCHL transmission in a substantial proportion of northern European families... - Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairmentChristophe Marcais
Laboratoire de Biochimie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Benite Cedex, France
J Clin Invest 115:2862-9. 2005..Our observations strongly support in humans a role for APOA5 in lipolysis regulation and in familial hyperchylomicronemia... - Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglyceridesPhilippa J Talmud
Division of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University Street, London WC1E 6JJ, UK
Hum Mol Genet 11:3039-46. 2002..The molecular mechanisms for these effects remain to be determined... - Apolipoprotein A5, a crucial determinant of plasma triglyceride levels, is highly responsive to peroxisome proliferator-activated receptor alpha activatorsNgoc Vu-Dac
Departement d Atherosclerose, U 545 INSERM, Institut Pasteur de Lille and Faculté de Pharmacie de Lille, 1 rue Calmette BP 245, 59019 Lille Cedex, France
J Biol Chem 278:17982-5. 2003..These findings demonstrate that APOA5 is a highly responsive peroxisome proliferator-activated receptor alpha target gene and support its role as a major mediator for how fibrates reduce plasma triglycerides in humans... - The amphioxus genome illuminates vertebrate origins and cephalochordate biologyLinda Z Holland
Marine Biology Research Division, Scripps Institution of Oceanography, La Jolla, California 92093 0202, USA
Genome Res 18:1100-11. 2008..Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates... - Most rare missense alleles are deleterious in humans: implications for complex disease and association studiesGregory V Kryukov
Division of Genetics, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02125, USA
Am J Hum Genet 80:727-39. 2007..Our results provide a justification for these types of candidate-gene (pathway) association studies and imply that mutation-selection balance may be a feasible evolutionary mechanism underlying some common diseases... - Transcriptional regulation of apolipoprotein A5 gene expression by the nuclear receptor RORalphaAnnelise Genoux
Departement d Atherosclerose, U 545 INSERM, Institut Pasteur de Lille and Faculté de Pharmacie de Lille, Lille Cedex, France
Arterioscler Thromb Vasc Biol 25:1186-92. 2005..In the present study, we identified the retinoic acid receptor-related orphan receptor-alpha (RORalpha) as a regulator of human APOA5 gene expression... - Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5Jamila Fruchart-Najib
Departement d Atherosclerose, UR 545 INSERM, Institut Pasteur de Lille et Université de Lille II, 1 rue du Pr Calmette BP 245, 59019 Lille Cedex, France
Biochem Biophys Res Commun 319:397-404. 2004..This shift of apoAV in VLDL appears to limit the increase of triglyceride by activating the lipoprotein lipase... - Insulin-mediated down-regulation of apolipoprotein A5 gene expression through the phosphatidylinositol 3-kinase pathway: role of upstream stimulatory factorMaxime Nowak
Parc Eurasanté Université de Lille 2, 885 Ave Eugène Avinée, 59120 Loos, France
Mol Cell Biol 25:1537-48. 2005..The effect of exogenous hyperinsulinemia in men showed a decrease in the plasma ApoAV level. These results suggest a potential contribution of the APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia... - The DNA sequence and biology of human chromosome 19Jane Grimwood
Stanford Human Genome Center, Department of Genetics, Stanford University School of Medicine, 975 California Avenue, Palo Alto, California 94304, USA
Nature 428:529-35. 2004.... - The DNA sequence and comparative analysis of human chromosome 5Jeremy Schmutz
Stanford Human Genome Center, Department of Genetics, Stanford University School of Medicine, 975 California Ave, Palo Alto, California 94304, USA
Nature 431:268-74. 2004..These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy... - Identification of a novel enhancer of brain expression near the apoE gene cluster by comparative genomicsPing Zheng
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021, USA
Biochim Biophys Acta 1676:41-50. 2004..These studies demonstrate that comparative sequence analysis is a successful strategy to predict candidate regulatory regions in vivo, although they do not imply that this element controls apoE expression physiologically... - Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipaseMartin Merkel
Department of Internal Medicine IUniversity Hospital Hamburg Eppendorf, 20246 Hamburg, Germany
J Biol Chem 280:21553-60. 2005..A direct interaction between LPL and apoAV was found by ligand blotting. It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycan-bound LPL for lipolysis... - A common allele on chromosome 9 associated with coronary heart diseaseRuth McPherson
Division of Cardiology, University of Ottawa Heart Institute, Ottawa K1Y4W7, Canada
Science 316:1488-91. 2007..Homozygotes for the risk allele make up 20 to 25% of Caucasians and have a approximately 30 to 40% increased risk of CHD... - Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDLStefano Romeo
Donald W Reynolds Cardiovascular Clinical Research Center, the Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
Nat Genet 39:513-6. 2007..Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history... - The liver X receptor ligand T0901317 down-regulates APOA5 gene expression through activation of SREBP-1cHeidelinde Jakel
Departement d Atherosclerose, UR545 INSERM, Institut Pasteur de Lille and Faculté de Pharmacie de Lille, 1 rue du Pr Calmette BP 245, 59019 Lille Cedex, France, Genfit SA, Loos F 59120, France
J Biol Chem 279:45462-9. 2004.... - Haplotype analysis of the apolipoprotein gene cluster on human chromosome 11Michael Olivier
Human and Molecular Genetics Center, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Genomics 83:912-23. 2004..These results highlight the complex genetic relationship between APOA5 and APOC3 and support the notion that APOA5 represents an independent risk gene affecting plasma triglyceride concentrations in humans... - Cathepsin L is required for endothelial progenitor cell-induced neovascularizationCarmen Urbich
Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany
Nat Med 11:206-13. 2005..We concluded that CathL has a critical role in the integration of circulating EPC into ischemic tissue and is required for EPC-mediated neovascularization... - Glucose regulates the expression of the apolipoprotein A5 geneMaxime Nowak
Institut Pasteur de Lille, Departement d Atherosclerose, Lille, France
J Mol Biol 380:789-98. 2008..We demonstrate that the APOA5 gene is up regulated by d-glucose and USF through phosphatase activation. These findings may provide a new cross-talk between glucose and lipid metabolism... - Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient miceLisa Sevenich
Institut für Molekulare Medizin und Zellforschung, Albert Ludwigs Universitat Freiburg, D 79104 Freiburg, Germany
Biol Chem 387:885-91. 2006..Human CTSL is expressed in the brain of these compound mutants, predominantly in neurons of the cerebral cortex and in Purkinje cells of the cerebellum, where it appears to prevent neuronal cell death... - Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1)Megan K Houseweart
Department of Genetics, School of Medicine, Stanford University, Stanford, California 94305, USA
J Neurobiol 56:315-27. 2003..They also suggest that the identification of cathepsin B substrates may further reveal the molecular basis for EPM1... - Array comparative genomic hybridization in patients with congenital diaphragmatic hernia: mapping of four CDH-critical regions and sequencing of candidate genes at 15q26.1-15q26.2Anne M Slavotinek
Department of Pediatrics, Division of Genetics, University of California, San Francisco, Room U585P, 533 Parnassus St, San Francisco, CA 94143 0748, USA
Eur J Hum Genet 14:999-1008. 2006..In addition, there is evidence for substantial genetic heterogeneity in CDH and diaphragmatic hernias can be non-penetrant in patients who have deletions involving CDH-critical regions... - Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathyBhaswati Pandit
Center for Molecular Cardiology, Department of Pediatrics and Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, New York 10029, USA
Nat Genet 39:1007-12. 2007..Our findings further implicate increased RAS signaling in pathological cardiomyocyte hypertrophy...
Research Grants
- Genetic and Genomic Analysis of apoAVLen Pennacchio; Fiscal Year: 2006..abstract_text> ..
- Generation of an In Vivo Human Genome Transcriptional Enhancer DatasetLen Pennacchio; Fiscal Year: 2009..Such a community resource is expected to significantly fill our void in gene regulatory annotation of the human genome and to decipher their mutation as a cause of human disease. . ..
- A High-Resolution Enhancer Atlas of the Developing ForebrainLEN ALEXANDER PENNACCHIO; Fiscal Year: 2010..These studies are likely to have implications in defining the role of these switches for normal brain function and how they go awry in human brain diseases. ..
- Generation of an In Vivo Human Genome Transcriptional Enhancer DatasetLen Pennacchio; Fiscal Year: 2009..Such a community resource is expected to significantly fill our void in gene regulatory annotation of the human genome and to decipher their mutation as a cause of human disease. . ..
- Generation of an In Vivo Human Genome Enhancer DatasetLEN ALEXANDER PENNACCHIO; Fiscal Year: 2010..The identification of positive signatures of enhancers in vivo is expected to significantly fill our void in gene regulatory annotation of the human genome and to decipher their mutation as a cause of human disease. ..