-
S G Gregory,
K F Barlow,
K E McLay,
R Kaul,
D Swarbreck, A Dunham,
C E Scott,
K L Howe,
K Woodfine,
C C A Spencer, [......],
W D H Burrill,
S M Clegg,
P Dhami,
O Dovey,
L M Faulkner,
S M Gribble,
C F Langford,
R D Pandian,
K M Porter,
E Prigmore
[show abstract]
[hide abstract]
ABSTRACT: The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
Nature 06/2006; 441(7091):315-21. · 36.28 Impact Factor
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S. G. Gregory,
K. F. Barlow,
K. E. McLay,
R. Kaul,
D. Swarbreck, A. Dunham,
C. E. Scott,
K. L. Howe,
K. Woodfine,
C. C. A. Spencer, [......],
R. Wooster,
I. Dunham,
N. P. Carter,
G. McVean,
M. T. Ross,
J. Harrow,
M. V. Olson,
S. Beck,
J. Rogers,
D. R. Bentley
[show abstract]
[hide abstract]
ABSTRACT: The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
Nature 05/2006; 441(7091):315-321. · 36.28 Impact Factor
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M. T. Ross,
D. V. Grafham,
A. J. Coffey,
S. Scherer,
K. McLay,
D. Muzny,
M. Platzer,
G. R. Howell,
C. Burrows,
C. P. Bird, [......],
A. Coulson,
D. L. Nelson,
G. Weinstock,
J. E. Sulston,
R. Durbin,
T. Hubbard,
R. A. Gibbs,
S. Beck,
J. Rogers,
D. R. Bentley
[show abstract]
[hide abstract]
ABSTRACT: The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
Nature 03/2005; 434:325-37. · 36.28 Impact Factor
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A Dunham,
L H Matthews,
J Burton,
J L Ashurst,
K L Howe,
K J Ashcroft,
D M Beare,
D C Burford,
S E Hunt,
S Griffiths-Jones, [......],
M W Wright,
L Young,
A Coulson,
R Durbin,
T Hubbard,
J E Sulston,
S Beck,
D R Bentley,
J Rogers,
M T Ross
[show abstract]
[hide abstract]
ABSTRACT: Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.
Nature 05/2004; 428(6982):522-8. · 36.28 Impact Factor
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A. Dunham,
L.H. Matthews,
J. Burton,
J.L. Ashurst,
K.L. Howe,
K.J. Ashcroft,
D.M. Beare,
D.C. Burford,
S.E. Hunt,
S.J. Griffiths-Jones, [......],
M.W. Wright,
L. Young,
A. Coulson,
R. Durbin,
T. Hubbard,
J.E. Sulston,
S. Beck,
D.R. Bentley,
J. Rogers,
M.T. Ross
Nature 04/2004; 428(6982):522-8. · 36.28 Impact Factor
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A. Dunham,
L. H. Matthews,
J. Burton,
J. L. Ashurst,
K. L. Howe,
K. J. Ashcroft,
D. M. Beare,
D. C. Burford,
S. E. Hunt,
S. Griffiths-Jones, [......],
M. W. Wright,
L. Young,
A. Coulson,
R. Durbin,
T. Hubbard,
J. E. Sulston,
S. Beck,
D. R. Bentley,
J. Rogers,
M. T. Ross
[show abstract]
[hide abstract]
ABSTRACT: Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.
Nature 03/2004; 428(6982):522-528. · 36.28 Impact Factor
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D R Bentley,
P Deloukas, A Dunham,
L French,
S G Gregory,
S J Humphray,
A J Mungall,
M T Ross,
N P Carter,
I Dunham, [......],
R G Taylor,
A A Thorpe,
E Tinsley,
G L Warry,
A Whittaker,
P Whittaker,
S H Williams,
T E Wilmer,
R Wooster,
C L Wright
[show abstract]
[hide abstract]
ABSTRACT: We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.
Nature 03/2001; 409(6822):942-3. · 36.28 Impact Factor
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E S Lander,
L M Linton,
B Birren,
C Nusbaum,
M C Zody,
J Baldwin,
K Devon,
K Dewar,
M Doyle,
W FitzHugh, [......],
K A Wetterstrand,
A Patrinos,
M J Morgan,
P de Jong,
J J Catanese,
K Osoegawa,
H Shizuya,
S Choi,
Y J Chen,
J Szustakowki
[show abstract]
[hide abstract]
ABSTRACT: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
Nature 03/2001; 409(6822):860-921. · 36.28 Impact Factor
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J D McPherson,
M Marra,
L Hillier,
R H Waterston,
A Chinwalla,
J Wallis,
M Sekhon,
K Wylie,
E R Mardis,
R K Wilson, [......],
A Shimizu,
K Shibuya,
J Kudoh,
S Minoshima,
J Ramser,
P Seranski,
C Hoff,
A Poustka,
R Reinhardt,
H Lehrach
[show abstract]
[hide abstract]
ABSTRACT: The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.
Nature 03/2001; 409(6822):934-41. · 36.28 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Contigs have been assembled, and over 2800 clones selected for sequencing for human chromosomes 9, 10 and 13. Using the FPC (FingerPrinted Contig) software, the contigs are assembled with markers and complete digest fingerprints, and the contigs are ordered and localised by a global framework. Publicly available resources have been used, such as, the 1998 International Gene Map for the framework and the GSC Human BAC fingerprint database for the majority of the fingerprints. Additional markers and fingerprints are generated in-house to supplement this data. To support the scale up of building maps, FPC V4.7 has been extended to use markers with the fingerprints for assembly of contigs, new clones and markers can be automatically added to existing contigs, and poorly assembled contigs are marked accordingly. To test the automatic assembly, a simulated complete digest of 110 Mb of concatenated human sequence was used to create datasets with varying coverage, length of clones, and types of error. When no error was introduced and a tolerance of 7 was used in assembly, the largest contig with no false positive overlaps has 9534 clones with 37 out-of-order clones, that is, the starting coordinates of adjacent clones are in the wrong order. This paper describes the new features in FPC, the scenario for building the maps of chromosomes 9, 10 and 13, and the results from the simulation.
Genome Research 12/2000; 10(11):1772-87. · 13.61 Impact Factor
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H E Steingruber, A Dunham,
A J Coffey,
S M Clegg,
G R Howell,
G L Maslen,
C E Scott,
R Gwilliam,
P J Hunt,
E C Sotheran,
E J Huckle,
S E Hunt,
P Dhami,
C Soderlund,
M A Leversha,
D R Bentley,
M T Ross
[show abstract]
[hide abstract]
ABSTRACT: We have established a landmark framework map over 20-25 Mb of the long arm of the human X chromosome using yeast artificial chromosome (YAC) clones. The map has approximately one landmark per 45 kb of DNA and stretches from DXS7531 in proximal Xq23 to DXS895 in proximal Xq26, connecting to published framework maps on its proximal and distal sides. There are three gaps in the framework map resulting from the failure to obtain clone coverage from the YAC resources available. Estimates of the maximum sizes of these gaps have been obtained. The four YAC contigs have been positioned and oriented using somatic-cell hybrids and fluorescence in situ hybridization, and the largest is estimated to cover approximately 15 Mb of DNA. The framework map is being used to assemble a sequence-ready map in large-insert bacterial clones, as part of an international effort to complete the sequence of the X chromosome. PAC and BAC contigs currently cover 18 Mb of the region, and from these, 12 Mb of finished sequence is available.
Genome Research 09/1999; 9(8):751-62. · 13.61 Impact Factor
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A J Coffey,
R A Brooksbank,
O Brandau,
T Oohashi,
G R Howell,
J M Bye,
A P Cahn,
J Durham,
P Heath,
P Wray, [......],
B H Behloradsky,
H Achatz,
J Murken,
R Fassler,
J Sumegi,
G Romeo,
M Vaudin,
M T Ross,
A Meindl,
D R Bentley
[show abstract]
[hide abstract]
ABSTRACT: X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.
Nature Genetics 11/1998; 20(2):129-35. · 35.53 Impact Factor
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S G Gregory,
K F Barlow,
K E McLay,
R Kaul,
D. Swarbreck, A Dunham,
C E Scott,
K L Howe,
K. Woodfine,
C C A Spencer, [......],
R Wooster,
I Dunham,
N P Carter,
G. McVean,
M T Ross,
J. Harrow,
M V Olson,
S Beck,
J Rogers,
D R Bentley
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ES Lander,
LM Linton,
B Birren,
C. Nusbaum,
MC Zody,
J Baldwin,
K Devon,
K Dewar,
M Doyle,
W FitzHugh, [......],
KH Wolfe,
SP Yang,
RF Yeh,
F Collins,
MS Guyer,
J Peterson,
A Felsenfeld,
KA Wetterstrand,
A Patrinos,
MJ Morgan
[show abstract]
[hide abstract]
ABSTRACT: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/62798/1/409860a0.pdf
Nature.
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N Craddock,
M. E. Hurles,
N. Cardin,
R. D. Pearson,
V. Plagnol,
S Robson,
D. Vukcevic,
C. Barnes,
D. F. Conrad,
E. Giannoulatou, [......],
J M M Howson,
D Hughes,
S Hunt,
J D Isaacs,
M. Jain,
D P Jewell,
T. Johnson,
J. D. Jolley,
I R Jones,
L. A. Jones et al
[show abstract]
[hide abstract]
ABSTRACT: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases
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E. S. Lander,
L. M. Linton,
B. Birren,
C. Nusbaum,
M. C. Zody,
J. Baldwin,
K. Devon,
K. Dewar,
M. Doyle,
W. FitzHugh, [......],
K. A. Wetterstrand,
A. Patrinos,
M. J. Morgan,
J. Szustakowki,
P. de Jong,
J. J. Catanese,
K. Osoegawa,
H. Shizuya,
S. Choi,
Y. J. Chen
[show abstract]
[hide abstract]
ABSTRACT: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
Nature. 409(6822):860-921.
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J. D. McPherson,
M. Marra,
L. Hillier,
R. H. Waterston,
A. Chinwalla,
J. Wallis,
M. Sekhon,
K. Wylie,
E. R. Mardis,
R. K. Wilson, [......],
A. Shimizu,
K. Shibuya,
J. Kudoh,
S. Minoshima,
J. Ramser,
P. Seranski,
C. Hoff,
A. Poustka,
R. Reinhardt,
H. Lehrach
[show abstract]
[hide abstract]
ABSTRACT: The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.
Nature. 409(6822):934-41.
-
J. D. McPherson,
M. Marra,
L. Hillier,
R. H. Waterston,
A. Chinwalla,
J. Wallis,
M. Sekhon,
K. Wylie,
E. R. Mardis,
R. K. Wilson, [......],
A. Shimizu,
K. Shibuya,
J. Kudoh,
S. Minoshima,
J. Ramser,
P. Seranski,
C. Hoff,
A. Poustka,
R. Reinhardt,
H. Lehrach
[show abstract]
[hide abstract]
ABSTRACT: The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.
Nature. 409(6822):934-41.
-
J. D. McPherson,
M. Marra,
L. Hillier,
R. H. Waterston,
A. Chinwalla,
J. Wallis,
M. Sekhon,
K. Wylie,
E. R. Mardis,
R. K. Wilson, [......],
A. Shimizu,
K. Shibuya,
J. Kudoh,
S. Minoshima,
J. Ramser,
P. Seranski,
C. Hoff,
A. Poustka,
R. Reinhardt,
H. Lehrach
[show abstract]
[hide abstract]
ABSTRACT: The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.
Nature. 409(6822):934-41.
-
J. D. McPherson,
M. Marra,
L. Hillier,
R. H. Waterston,
A. Chinwalla,
J. Wallis,
M. Sekhon,
K. Wylie,
E. R. Mardis,
R. K. Wilson, [......],
A. Shimizu,
K. Shibuya,
J. Kudoh,
S. Minoshima,
J. Ramser,
P. Seranski,
C. Hoff,
A. Poustka,
R. Reinhardt,
H. Lehrach
[show abstract]
[hide abstract]
ABSTRACT: The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.
Nature. 409(6822):934-41.
