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Article ; Online: A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas.

2020 Volume 149, Issue 3, Page(s) 437–445

Abstract: Purpose: This study was performed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the immunomodulatory agent, lenalidomide, when administered daily during 6 weeks of radiation therapy to children with newly diagnosed ... ...

Abstract	Purpose: This study was performed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the immunomodulatory agent, lenalidomide, when administered daily during 6 weeks of radiation therapy to children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) PATIENTS & METHODS: Children and young adults < 22 years of age with newly diagnosed disease and no prior chemotherapy or radiation therapy were eligible. Children with HGG were required to have an inoperable or incompletely resected tumor. Eligible patients received standard radiation therapy to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide daily during radiation therapy in a standard 3 + 3 Phase I dose escalation design. Following completion of radiation therapy, patients had a 2-week break followed by maintenance lenalidomide at 116 mg/m Results: Twenty-nine patients (age range 4-19 years) were enrolled; 24 were evaluable for dose finding (DIPG, n = 13; HGG, n = 11). The MTD was not reached at doses of lenalidomide up to 116 mg/m Conclusion: The RP2D of lenalidomide administered daily during radiation therapy is 116 mg/m
MeSH term(s)	Adolescent ; Adult ; Angiogenesis Inhibitors/pharmacokinetics ; Angiogenesis Inhibitors/therapeutic use ; Brain Stem Neoplasms/pathology ; Brain Stem Neoplasms/therapy ; Chemoradiotherapy/methods ; Child ; Child, Preschool ; Diffuse Intrinsic Pontine Glioma/pathology ; Diffuse Intrinsic Pontine Glioma/therapy ; Female ; Follow-Up Studies ; Humans ; Lenalidomide/pharmacokinetics ; Lenalidomide/therapeutic use ; Male ; Maximum Tolerated Dose ; Prognosis ; Tissue Distribution ; Young Adult
Chemical Substances	Angiogenesis Inhibitors ; Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2020-10-11
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-020-03627-0
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Article: TOPO TA is A-OK: a test of phylogenetic bias in fungal environmental clone library construction.

Taylor, D Lee / Herriott, Ian C / Long, James / O'Neill, Keith

Environmental microbiology

2007 Volume 9, Issue 5, Page(s) 1329–1334

Abstract: TA cloning methods are widely used in analyses of environmental microbial diversity, yet the potential of TA methods to yield phylogenetically biased results has received little attention. To test for a TA bias, we constructed clone libraries of fungal ... ...

Abstract	TA cloning methods are widely used in analyses of environmental microbial diversity, yet the potential of TA methods to yield phylogenetically biased results has received little attention. To test for a TA bias, we constructed clone libraries of fungal amplicons spanning the ribosomal internally transcribed spacer (ITS) and partial large subunit (LSU) from 92 boreal forest soil DNA extracts using two contrasting methods: the Invitrogen TOPO-TA system and the Lucigen PCR-SMART system. The Lucigen system utilizes blunt-ended rather than TA cloning and transcription terminators to reduce biases due to toxicity of expressed inserts. We analysed 588 clone sequences from the two libraries. Species diversity estimators applied to operational taxonomical units (OTUs) were slightly higher for Invitrogen than Lucigen, but confidence intervals for accumulation curves overlapped. Abundances of OTUs were correlated between the libraries (r(2) = 0.5, P < 0.0001), but certain OTUs had contrasting abundances in the two libraries and a likelihood ratio test rejected homogeneity of the OTU counts. We constructed parsimony and Bayesian trees from aligned LSU regions, and the 'phylogenetic test' revealed that lineage representation was not significantly different between the two libraries. We conclude that characterization of this fungal community was fairly robust to cloning method and no biases due to TA cloning were found.
MeSH term(s)	Cloning, Molecular/methods ; Fungi/genetics ; Gene Library ; Phylogeny ; Ribosomes/classification ; Sequence Analysis, DNA/instrumentation ; Soil Microbiology
Language	English
Publishing date	2007-05
Publishing country	England
Document type	Evaluation Studies ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2020213-1
ISSN	1462-2920 ; 1462-2912
ISSN (online)	1462-2920
ISSN	1462-2912
DOI	10.1111/j.1462-2920.2007.01253.x
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Article: TOPO TA is A-OK: a test of phylogenetic bias in fungal environmental clone library construction

Taylor, D. Lee / Herriott, Ian C / Long, James / O'Neill, Keith

Environmental microbiology. 2007 May, v. 9, no. 5

2007

Abstract	TA cloning methods are widely used in analyses of environmental microbial diversity, yet the potential of TA methods to yield phylogenetically biased results has received little attention. To test for a TA bias, we constructed clone libraries of fungal amplicons spanning the ribosomal internally transcribed spacer (ITS) and partial large subunit (LSU) from 92 boreal forest soil DNA extracts using two contrasting methods: the Invitrogen TOPO-TA system and the Lucigen PCR-SMART system. The Lucigen system utilizes blunt-ended rather than TA cloning and transcription terminators to reduce biases due to toxicity of expressed inserts. We analysed 588 clone sequences from the two libraries. Species diversity estimators applied to operational taxonomical units (OTUs) were slightly higher for Invitrogen than Lucigen, but confidence intervals for accumulation curves overlapped. Abundances of OTUs were correlated between the libraries (r² = 0.5, P < 0.0001), but certain OTUs had contrasting abundances in the two libraries and a likelihood ratio test rejected homogeneity of the OTU counts. We constructed parsimony and Bayesian trees from aligned LSU regions, and the 'phylogenetic test' revealed that lineage representation was not significantly different between the two libraries. We conclude that characterization of this fungal community was fairly robust to cloning method and no biases due to TA cloning were found.
Keywords	DNA ; Otus ; boreal forests ; clones ; confidence interval ; environmental assessment ; forest soils ; fungi ; libraries ; species diversity
Language	English
Dates of publication	2007-05
Size	p. 1329-1334.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	2020213-1
ISSN	1462-2920 ; 1462-2912
ISSN (online)	1462-2920
ISSN	1462-2912
DOI	10.1111/j.1462-2920.2007.01253.x
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Article: The ner gene of Photorhabdus: effects on primary-form-specific phenotypes and outer membrane protein composition.

O'Neill, Keith H / Roche, Declan M / Clarke, David J / Dowds, Barbara C A

Journal of bacteriology

2001 Volume 184, Issue 11, Page(s) 3096–3105

Abstract: The nematode-bacterium complex of Heterorhabditis-Photorhabdus is pathogenic to insect larvae. The bacteria undergo a form of phenotypic switching whereby the primary form, at the stationary phase of the growth cycle, makes a range of products and has ... ...

Abstract	The nematode-bacterium complex of Heterorhabditis-Photorhabdus is pathogenic to insect larvae. The bacteria undergo a form of phenotypic switching whereby the primary form, at the stationary phase of the growth cycle, makes a range of products and has the capacity to support nematode growth, whereas the secondary form does not express these phenotypes. The work described here investigated the mechanism regulating phenotypic variation by transforming the primary cells with secondary-form DNA on a low-copy-number vector and screening for colonies which did not produce the yellow pigment characteristic of primaries. Four transformants all carrying the same gene were found to loose primary-form-specific characteristics, and the gene was sequenced and identified as ner, a regulatory gene in gram-negative bacteria and their phages. Unexpectedly, inactivation of the endogenous gene in the secondaries did not cause them to revert to the primary phenotype, and the gene was expressed in the primary form as well as the secondary form during exponential but not stationary phase and deregulated in the plasmid-bearing primary form. These and other pieces of evidence indicate that the endogenous ner gene is not responsible for the secondary phenotype, but that ner, when overexpressed, can repress expression of primary phenotypes at stationary phase. Inactivation of the endogenous ner gene in the primary form affected the outer membrane protein profile. A number of outer membrane proteins displayed differential accumulation in the primary and secondary forms at stationary phase, and two of the primary-form-specific proteins were absent from the ner primary strain.
MeSH term(s)	Amino Acid Sequence ; Bacterial Outer Membrane Proteins/chemistry ; Bacterial Outer Membrane Proteins/genetics ; Base Sequence ; Electrophoresis, Polyacrylamide Gel ; Gene Deletion ; Genes, Bacterial ; Genes, Regulator ; Molecular Sequence Data ; Open Reading Frames ; Phenotype ; Photorhabdus/chemistry ; Photorhabdus/genetics ; Photorhabdus/growth & development ; Sequence Alignment
Chemical Substances	Bacterial Outer Membrane Proteins
Language	English
Publishing date	2001-10-13
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.184.11.3096-3105.2002
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Article: Strain characteristics of Streptococcus pneumoniae carriage and invasive disease isolates during a cluster-randomized clinical trial of the 7-valent pneumococcal conjugate vaccine.

Lipsitch, Marc / O'Neill, Keith / Cordy, Derrick / Bugalter, Boris / Trzcinski, Krzysztof / Thompson, Claudette M / Goldstein, Richard / Pelton, Stephen / Huot, Heather / Bouchet, Valerie / Reid, Raymond / Santosham, Mathuram / O'Brien, Katherine L

The Journal of infectious diseases

2007 Volume 196, Issue 8, Page(s) 1221–1227

Abstract: Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) has led to significant reductions in disease while changing pneumococcal population dynamics via herd immunity and serotype replacement. We performed multilocus sequence typing (MLST) on ... ...

Abstract	Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) has led to significant reductions in disease while changing pneumococcal population dynamics via herd immunity and serotype replacement. We performed multilocus sequence typing (MLST) on 590 pneumococcal isolates obtained during the American Indian clinical trial of PCV7, in which communities were randomized for eligible children to receive either PCV7 or a meningococcal conjugate vaccine (MCV). Sequence types (STs) were analyzed to determine the impact of the vaccine on pneumococcal population structure and to assess the possible impact of pneumococcal genetic background on vaccine effects. One hundred forty-three STs were obtained, the most frequent being ST199, the only one that included vaccine serotypes (VTs), non-vaccine-associated nonvaccine serotypes (NVA/NVTs), and vaccine-associated serotypes (VATs). Serotype replacement observed in the PCV communities was due to a diverse population of STs, most of which also existed in the MCV communities. Possible capsular switching to create novel ST associations with NVA/NVTs was detected only once. Reductions in VTs and changes in VATs in PCV communities did not show evidence of variation by ST, after accounting for lower vaccine effectiveness against serotype 19F. These observations suggest the hypothesis that the vaccine acts as a "serotype filter": its effect on a particular strain can be predicted on the basis of the serotype of the strain, with little effect of genetic background (as assessed by MLST) over and above capsule. If sustained, such patterns provide some cause for optimism that rapid evolution of PCV escape strains with drug resistance or high virulence is unlikely.
MeSH term(s)	Carrier State/microbiology ; Genotype ; Heptavalent Pneumococcal Conjugate Vaccine ; Humans ; Immunity, Herd ; Indians, North American ; Infant ; Meningococcal Vaccines/therapeutic use ; Nasopharynx/microbiology ; Pneumococcal Infections/classification ; Pneumococcal Vaccines/therapeutic use ; Serotyping ; Streptococcus pneumoniae/classification ; Streptococcus pneumoniae/genetics ; Streptococcus pneumoniae/immunology ; Vaccines, Conjugate/therapeutic use
Chemical Substances	Heptavalent Pneumococcal Conjugate Vaccine ; Meningococcal Vaccines ; Pneumococcal Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2007-09-17
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1086/521831
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Article: Assembly of polymorphic genomes: algorithms and application to Ciona savignyi.

Vinson, Jade P / Jaffe, David B / O'Neill, Keith / Karlsson, Elinor K / Stange-Thomann, Nicole / Anderson, Scott / Mesirov, Jill P / Satoh, Nori / Satou, Yutaka / Nusbaum, Chad / Birren, Bruce / Galagan, James E / Lander, Eric S

Genome research

2005 Volume 15, Issue 8, Page(s) 1127–1135

Abstract: Whole-genome assembly is now used routinely to obtain high-quality draft sequence for the genomes of species with low levels of polymorphism. However, genome assembly remains extremely challenging for highly polymorphic species. The difficulty arises ... ...

Abstract	Whole-genome assembly is now used routinely to obtain high-quality draft sequence for the genomes of species with low levels of polymorphism. However, genome assembly remains extremely challenging for highly polymorphic species. The difficulty arises because two divergent haplotypes are sequenced together, making it difficult to distinguish alleles at the same locus from paralogs at different loci. We present here a method for assembling highly polymorphic diploid genomes that involves assembling the two haplotypes separately and then merging them to obtain a reference sequence. Our method was developed to assemble the genome of the sea squirt Ciona savignyi, which was sequenced to a depth of 12.7 x from a single wild individual. By comparing finished clones of the two haplotypes we determined that the sequenced individual had an extremely high heterozygosity rate, averaging 4.6% with significant regional variation and rearrangements at all physical scales. Applied to these data, our method produced a reference assembly covering 157 Mb, with N50 contig and scaffold sizes of 47 kb and 989 kb, respectively. Alignment of ESTs indicates that 88% of loci are present at least once and 81% exactly once in the reference assembly. Our method represented loci in a single copy more reliably and achieved greater contiguity than a conventional whole-genome assembly method.
MeSH term(s)	Algorithms ; Animals ; Base Sequence ; Cloning, Molecular/methods ; Diploidy ; Expressed Sequence Tags ; Genome ; Haplotypes/genetics ; Heterozygote ; Molecular Sequence Data ; Polymerase Chain Reaction/methods ; Reproducibility of Results ; Urochordata/genetics
Language	English
Publishing date	2005-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.3722605
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Article ; Online: Genomic representations using concatenates of Type IIB restriction endonuclease digestion fragments.

Tengs, Torstein / LaFramboise, Thomas / Den, Robert B / Hayes, David N / Zhang, Jianhua / DebRoy, Saikat / Gentleman, Robert C / O'Neill, Keith / Birren, Bruce / Meyerson, Matthew

Nucleic acids research

2004 Volume 32, Issue 15, Page(s) e121

Abstract: We have developed a method for genomic representation using Type IIB restriction endonucleases. Representation by concatenation of restriction digests, or RECORD, is an approach to sample the fragments generated by cleavage with these enzymes. Here, we ... ...

Abstract	We have developed a method for genomic representation using Type IIB restriction endonucleases. Representation by concatenation of restriction digests, or RECORD, is an approach to sample the fragments generated by cleavage with these enzymes. Here, we show that the RECORD libraries may be used for digital karyotyping and for pathogen identification by computational subtraction.
MeSH term(s)	Bacteria/genetics ; Bacteria/isolation & purification ; Computational Biology ; Computer Simulation ; DNA, Concatenated/genetics ; Deoxyribonucleases, Type II Site-Specific/metabolism ; Genome, Human ; Genomic Library ; Genomics/methods ; Humans ; Karyotyping/methods ; Markov Chains ; Polymerase Chain Reaction ; Viruses/genetics ; Viruses/isolation & purification
Chemical Substances	DNA, Concatenated ; Deoxyribonucleases, Type II Site-Specific (EC 3.1.21.4)
Language	English
Publishing date	2004-08-25
Publishing country	England
Document type	Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2205588-5
ISSN	1362-4962 ; 1746-8272 ; 0305-1048 ; 0261-3166
ISSN (online)	1362-4962 ; 1746-8272
ISSN	0305-1048 ; 0261-3166
DOI	10.1093/nar/gnh120
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Article: Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.

Thomas, Roman K / Nickerson, Elizabeth / Simons, Jan F / Jänne, Pasi A / Tengs, Torstein / Yuza, Yuki / Garraway, Levi A / LaFramboise, Thomas / Lee, Jeffrey C / Shah, Kinjal / O'Neill, Keith / Sasaki, Hidefumi / Lindeman, Neal / Wong, Kwok-Kin / Borras, Ana M / Gutmann, Edward J / Dragnev, Konstantin H / DeBiasi, Ralph / Chen, Tzu-Hsiu /

Glatt, Karen A / Greulich, Heidi / Desany, Brian / Lubeski, Christine K / Brockman, William / Alvarez, Pablo / Hutchison, Stephen K / Leamon, J H / Ronan, Michael T / Turenchalk, Gregory S / Egholm, Michael / Sellers, William R / Rothberg, Jonathan M / Meyerson, Matthew

Nature medicine

2006 Volume 12, Issue 7, Page(s) 852–855

Abstract: The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence ... ...

Abstract	The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence variations by independent and parallel sampling of multiple representatives of a given DNA fragment. This technology can thereby facilitate accurate molecular diagnosis of heterogeneous cancer specimens and enable patient selection for targeted cancer therapies.
MeSH term(s)	Base Sequence ; Chromosome Mapping/methods ; DNA, Neoplasm/genetics ; Humans ; Molecular Sequence Data ; Mutation ; Neoplasms/diagnosis ; Neoplasms/genetics ; Sensitivity and Specificity
Chemical Substances	DNA, Neoplasm
Language	English
Publishing date	2006-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm1437
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Article ; Online: Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain.

Lee, Jeffrey C / Vivanco, Igor / Beroukhim, Rameen / Huang, Julie H Y / Feng, Whei L / DeBiasi, Ralph M / Yoshimoto, Koji / King, Jennifer C / Nghiemphu, Phioanh / Yuza, Yuki / Xu, Qing / Greulich, Heidi / Thomas, Roman K / Paez, J Guillermo / Peck, Timothy C / Linhart, David J / Glatt, Karen A / Getz, Gad / Onofrio, Robert /

Ziaugra, Liuda / Levine, Ross L / Gabriel, Stacey / Kawaguchi, Tomohiro / O'Neill, Keith / Khan, Haumith / Liau, Linda M / Nelson, Stanley F / Rao, P Nagesh / Mischel, Paul / Pieper, Russell O / Cloughesy, Tim / Leahy, Daniel J / Sellers, William R / Sawyers, Charles L / Meyerson, Matthew / Mellinghoff, Ingo K

PLoS medicine

2006 Volume 3, Issue 12, Page(s) e485

Abstract: Background: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant ... ...

Abstract	Background: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. Methods and findings: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. Conclusions: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma.
MeSH term(s)	Animals ; Astrocytes/drug effects ; Astrocytes/metabolism ; Binding Sites/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Cell Survival/genetics ; Cells, Cultured ; Erlotinib Hydrochloride ; Gene Expression Regulation, Neoplastic/drug effects ; Glioblastoma/genetics ; Glioblastoma/pathology ; Humans ; Mice ; Mice, Nude ; Models, Molecular ; Mutation, Missense ; NIH 3T3 Cells ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Phosphorylation ; Protein Binding ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Structure, Tertiary ; Quinazolines/chemistry ; Quinazolines/metabolism ; Quinazolines/pharmacology ; Receptor, Epidermal Growth Factor/chemistry ; Receptor, Epidermal Growth Factor/genetics ; Receptor, Epidermal Growth Factor/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection
Chemical Substances	Protein Kinase Inhibitors ; Quinazolines ; Erlotinib Hydrochloride (DA87705X9K) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1)
Language	English
Publishing date	2006-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.0030485
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Article ; Online: DNA sequence and analysis of human chromosome 18.

Nusbaum, Chad / Zody, Michael C / Borowsky, Mark L / Kamal, Michael / Kodira, Chinnappa D / Taylor, Todd D / Whittaker, Charles A / Chang, Jean L / Cuomo, Christina A / Dewar, Ken / FitzGerald, Michael G / Yang, Xiaoping / Abouelleil, Amr / Allen, Nicole R / Anderson, Scott / Bloom, Toby / Bugalter, Boris / Butler, Jonathan / Cook, April /

DeCaprio, David / Engels, Reinhard / Garber, Manuel / Gnirke, Andreas / Hafez, Nabil / Hall, Jennifer L / Norman, Catherine Hosage / Itoh, Takehiko / Jaffe, David B / Kuroki, Yoko / Lehoczky, Jessica / Lui, Annie / Macdonald, Pendexter / Mauceli, Evan / Mikkelsen, Tarjei S / Naylor, Jerome W / Nicol, Robert / Nguyen, Cindy / Noguchi, Hideki / O'Leary, Sinéad B / O'Neill, Keith / Piqani, Bruno / Smith, Cherylyn L / Talamas, Jessica A / Topham, Kerri / Totoki, Yasushi / Toyoda, Atsushi / Wain, Hester M / Young, Sarah K / Zeng, Qiandong / Zimmer, Andrew R / Fujiyama, Asao / Hattori, Masahira / Birren, Bruce W / Sakaki, Yoshiyuki / Lander, Eric S

Nature

2005 Volume 437, Issue 7058, Page(s) 551–555

Abstract: Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and ... ...

Abstract	Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.
MeSH term(s)	Aneuploidy ; Animals ; Chromosomes, Human, Pair 18/genetics ; Conserved Sequence/genetics ; CpG Islands/genetics ; DNA/genetics ; Exons/genetics ; Expressed Sequence Tags ; Genes/genetics ; Genome, Human ; Humans ; Introns/genetics ; Molecular Sequence Data ; Sequence Analysis, DNA ; Synteny
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2005-09-22
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature03983
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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