scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Initial sequencing and analysis of the human genome.

Eric S. Lander1, Lauren Linton1, Bruce W. Birren1, Chad Nusbaum1  +245 moreInstitutions (29)
15 Feb 2001-Nature (Nature Publishing Group)-Vol. 409, Iss: 6822, pp 860-921
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
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.

Content maybe subject to copyright    Report

Citations
More filters
Journal ArticleDOI
TL;DR: The connection between functional specificity and biochemical properties including glycosylation, phosphorylation and acetylation of Sp1-related factors are focused on.

457 citations

Journal ArticleDOI
09 Aug 2002-Cell
TL;DR: A genetic system to recover many new L1 insertions in somatic cells was developed that faithfully mimic many aspects of L1s that accumulated since the primate radiation, and short identical sequences were shared between the donor and the target site's 3' end, suggesting a mechanistic model that helps explain the structure of L 1 insertions.

454 citations


Cites background from "Initial sequencing and analysis of ..."

  • ...Most de novo insertions have primary target sequence specificity, and overall lengths and genomic contexts, consistent with primate-specific L1s (Lander et al., 2001; Szak et al., 2002)....

    [...]

  • ...De novo L1 targeting frequencies into different repetitive familiesous findings that the length of poly(A) tails is inversely correlated with the elements’ age (Ovchinnikov et al., approximate the composition of the human genome (Lander et al., 2001).2001)....

    [...]

  • ...Genomic L1s have probably acquired new 5 ends by a similar mechanism (Lander et al., 2001)....

    [...]

  • ...Proceeding from genome are packaged in heterochromatin (Lander et al., 2001)....

    [...]

  • ...Lander et al., 2001; Szak et al., 2002)....

    [...]

Journal ArticleDOI
01 Oct 2001-Genetics
TL;DR: This discrete description of Base composition is spatially structured in mammalian genomes and three major classes of genomic fragments with low, median, and high GC content, respectively, are defined.
Abstract: BASE composition is spatially structured in mammalian genomes. From sodium chloride centrifugation experiments, Bernardi et al . ([1985][1]) defined three major classes of genomic fragments with low, median, and high GC content, respectively, and called them isochores. This discrete description now

453 citations

Journal ArticleDOI
TL;DR: It is suggested that EST-SSRs can be successfully used for a variety of purposes, and may actually prove superior to SSR markers extracted from genomic libraries for diversity estimation and transferability.
Abstract: Nearly 900 SSRs (simple sequence repeats) were identified among 15,000 ESTs (expressed sequence tags) belonging to bread wheat ( Triticum aestivum L.). The SSRs were defined by their minimum length, which ranged from 14 to 21 bp. The maximum length ranged from 24 to 87 bp depending upon the length of the repeat unit itself (1–7 bp). The average density of SSRs was one SSR per 9.2 kb of EST sequence screened. The trinucleotide repeats were the most abundant SSRs detected. As a representative sample, 78 primer pairs were designed, which were also used to screen the dbEST entries for Hordeum vulgare and Triticum tauschii (donor of the D-genome of cultivated wheat) using a cut-off E (expectation) value of 0.01. On the basis of in silico analysis, up to 55.12% of the primer pairs exhibited transferability from Triticum to Hordeum, indicating that the sequences flanking the SSRs are not only conserved within a single genus but also between related genera in Poaceae. Primer pairs for the 78 SSRs were synthesized and used successfully for the study of (1) their transferability to 18 related wild species and five cereal species (barley, oat, rye, rice and maize); and (2) polymorphism between the parents of four mapping populations available with us. A subset of 20 EST-SSR primers was also used to assess genetic diversity in a collection of 52 elite exotic wheat genotypes. This was done with a view to compare their utility relative to other molecular markers (gSSRs, AFLPs, and SAMPL) previously used by us for the same purpose with the same set of 52 bread wheat genotypes. Although only a low level of polymorphism was detected, relative to that observed with genomic SSRs, the study suggested that EST-SSRs can be successfully used for a variety of purposes, and may actually prove superior to SSR markers extracted from genomic libraries for diversity estimation and transferability.

453 citations

Journal ArticleDOI
28 Jun 2012-Nature
TL;DR: The sequencing and assembly of the bonobo genome is reported to study its evolutionary relationship with the chimpanzee and human genomes, and it is found that more than three per cent of the human genome is more closely related to either theBonobo or the chimpanzees genome than these are to each other.
Abstract: Sequencing of the bonobo genome shows that more than three per cent of the human genome is more closely related to either the bonobo genome or the chimpanzee genome than those genomes are to each other. The chimpanzee and the bonobo are our species' two closest living relatives. This paper reports the genome sequence of the bonobo, the last ape to be sequenced. Comparative genomic analyses reveal that more than 3% of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. The results shed light on the ancestry of the two ape species and might eventually help us to understand the genetic basis of phenotypes that humans share with one or the other ape species. Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours1,2,3,4, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other.

452 citations

References
More filters
Journal ArticleDOI
TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

70,111 citations

Journal ArticleDOI
TL;DR: The definition and use of family-specific, manually curated gathering thresholds are explained and some of the features of domains of unknown function (also known as DUFs) are discussed, which constitute a rapidly growing class of families within Pfam.
Abstract: Pfam is a widely used database of protein families and domains. This article describes a set of major updates that we have implemented in the latest release (version 24.0). The most important change is that we now use HMMER3, the latest version of the popular profile hidden Markov model package. This software is approximately 100 times faster than HMMER2 and is more sensitive due to the routine use of the forward algorithm. The move to HMMER3 has necessitated numerous changes to Pfam that are described in detail. Pfam release 24.0 contains 11,912 families, of which a large number have been significantly updated during the past two years. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/).

14,075 citations

Journal ArticleDOI
J. Craig Venter1, Mark Raymond Adams1, Eugene W. Myers1, Peter W. Li1  +269 moreInstitutions (12)
16 Feb 2001-Science
TL;DR: Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems are indicated.
Abstract: A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

12,098 citations

Journal ArticleDOI
TL;DR: This letter extends the heuristic homology algorithm of Needleman & Wunsch (1970) to find a pair of segments, one from each of two long sequences, such that there is no other Pair of segments with greater similarity (homology).

10,262 citations

Journal ArticleDOI
09 Apr 1981
TL;DR: The complete sequence of the 16,569-base pair human mitochondrial genome is presented and shows extreme economy in that the genes have none or only a few noncoding bases between them, and in many cases the termination codons are not coded in the DNA but are created post-transcriptionally by polyadenylation of the mRNAs.
Abstract: The complete sequence of the 16,569-base pair human mitochondrial genome is presented. The genes for the 12S and 16S rRNAs, 22 tRNAs, cytochrome c oxidase subunits I, II and III, ATPase subunit 6, cytochrome b and eight other predicted protein coding genes have been located. The sequence shows extreme economy in that the genes have none or only a few noncoding bases between them, and in many cases the termination codons are not coded in the DNA but are created post-transcriptionally by polyadenylation of the mRNAs.

8,783 citations