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PubMed2006

Doubling genome size without polyploidization: dynamics of retrotransposition-driven genomic expansions in Oryza australiensis, a wild relative of rice.

Retrotransposons are the main components of eukaryotic genomes, representing up to 80% of some large plant genomes. These mobile elements transpose via a "copy and paste" mechanism, thus increasing their copy number while active. Their accumulation is now accepted as the main factor of genome size increase in higher eukaryotes, besides polyploidy. However, the dynamics of this process are poorly understood. In this study, we show that Oryza australiensis, a wild relative of the Asian cultivated rice O. sativa, has undergone recent bursts of three LTR-retrotransposon families. This genome has accumulated more than 90,000 retrotransposon copies during the last three million years, leading to a rapid twofold increase of its size. In addition, phenetic analyses of these retrotransposons clearly confirm that the genomic bursts occurred posterior to the radiation of the species. This provides direct evidence of retrotransposon-mediated variation of genome size within a plant genus.

Base Sequence↗

PubMed1998

Transposable elements and genome organization: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence.

We conducted a genome-wide survey of Saccharomyces cerevisiae retrotransposons and identified a total of 331 insertions, including 217 Ty1, 34 Ty2, 41 Ty3, 32 Ty4, and 7 Ty5 elements. Eighty-five percent of insertions were solo long terminal repeats (LTRs) or LTR fragments. Overall, retrotransposon sequences constitute >377 kb or 3.1% of the genome. Independent evolution of retrotransposon sequences was evidenced by the identification of a single-base pair insertion/deletion that distinguishes the highly similar Ty1 and Ty2 LTRs and the identification of a distinct Ty1 subfamily (Ty1'). Whereas Ty1, Ty2, and Ty5 LTRs displayed a broad range of sequence diversity (typically ranging from 70%-99% identity), Ty3 and Ty4 LTRs were highly similar within each element family (most sharing >96% nucleotide identity). Therefore, Ty3 and Ty4 may be more recent additions to the S. cerevisiae genome and perhaps entered through horizontal transfer or past polyploidization events. Distribution of Ty elements is distinctly nonrandom: 90% of Ty1, 82% of Ty2, 95% of Ty3, and 88% of Ty4 insertions were found within 750 bases of tRNA genes or other genes transcribed by RNA polymerase III. tRNA genes are the principle determinant of retrotransposon distribution, and there is, on average, 1.2 insertions per tRNA gene. Evidence for recombination was found near many Ty elements, particularly those not associated with tRNA gene targets. For these insertions, 5'- and 3'-flanking sequences were often duplicated and rearranged among multiple chromosomes, indicating that recombination between retrotransposons can influence genome organization. S. cerevisiae offers the first opportunity to view organizational and evolutionary trends among retrotransposons at the genome level, and we hope our compiled data will serve as a starting point for further investigation and for comparison to other, more complex genomes.

Base Sequence↗

PubMed2003

Whole-genome sequence assembly for mammalian genomes: Arachne 2.

We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program, allowing for assembly of mammalian-size genomes, and also improving the assembly of smaller genomes. Three principal changes were simultaneously made and applied to the assembly of the mouse genome, during a six-month period of development: (1) Supercontigs (scaffolds) were iteratively broken and rejoined using several criteria, yielding a 64-fold increase in length (N50), and apparent elimination of all global misjoins; (2) gaps between contigs in supercontigs were filled (partially or completely) by insertion of reads, as suggested by pairing within the supercontig, increasing the N50 contig length by 50%; (3) memory usage was reduced fourfold. The outcome of this mouse assembly and its analysis are described in (Mouse Genome Sequencing Consortium 2002).

Animals↗

PubMed1998

Comparison of sample sequences of the Salmonella typhi genome to the sequence of the complete Escherichia coli K-12 genome.

Raw sequence data representing the majority of a bacterial genome can be obtained at a tiny fraction of the cost of a completed sequence. To demonstrate the utility of such a resource, 870 single-stranded M13 clones were sequenced from a shotgun library of the Salmonella typhi Ty2 genome. The sequence reads averaged over 400 bases and sampled the genome with an average spacing of once every 5,000 bases. A total of 339,243 bases of unique sequence was generated (approximately 7% representation). The sample of 870 sequences was compared to the complete Escherichia coli K-12 genome and to the rest of the GenBank database, which can also be considered a collection of sampled sequences. Despite the incomplete S. typhi data set, interesting categories could easily be discerned. Sixteen percent of the sequences determined from S. typhi had close homologs among known Salmonella sequences (P < 1e-40 in BlastX or BlastN), reflecting the proportion of these genomes that have been sequenced previously; 277 sequences (32%) had no apparent orthologs in the complete E. coli K-12 genome (P > 1e-20), of which 155 sequences (18%) had no close similarities to any sequence in the database (P > 1e-5). Eight of the 277 sequences had similarities to genes in other strains of E. coli or plasmids, and six sequences showed evidence of novel phage lysogens or sequence remnants of phage integrations, including a member of the lambda family (P < 1e-15). Twenty-three sample sequences had a significantly closer similarity a sequence in the database from organisms other than the E. coli/Salmonella clade (which includes Shigella and Citrobacter). These sequences are new candidate lateral transfer events to the S. typhi lineage or deletions on the E. coli K-12 lineage. Eleven putative junctions of insertion/deletion events greater than 100 bp were observed in the sample, indicating that well over 150 such events may distinguish S. typhi from E. coli K-12. The need for automatic methods to more effectively exploit sample sequences is discussed.

Bacteriophages↗

PubMed2006

The Methanosarcina barkeri genome: comparative analysis with Methanosarcina acetivorans and Methanosarcina mazei reveals extensive rearrangement within methanosarcinal genomes.

We report here a comparative analysis of the genome sequence of Methanosarcina barkeri with those of Methanosarcina acetivorans and Methanosarcina mazei. The genome of M. barkeri is distinguished by having an organization that is well conserved with respect to the other Methanosarcina spp. in the region proximal to the origin of replication, with interspecies gene similarities as high as 95%. However, it is disordered and marked by increased transposase frequency and decreased gene synteny and gene density in the distal semigenome. Of the 3,680 open reading frames (ORFs) in M. barkeri, 746 had homologs with better than 80% identity to both M. acetivorans and M. mazei, while 128 nonhypothetical ORFs were unique (nonorthologous) among these species, including a complete formate dehydrogenase operon, genes required for N-acetylmuramic acid synthesis, a 14-gene gas vesicle cluster, and a bacterial-like P450-specific ferredoxin reductase cluster not previously observed or characterized for this genus. A cryptic 36-kbp plasmid sequence that contains an orc1 gene flanked by a presumptive origin of replication consisting of 38 tandem repeats of a 143-nucleotide motif was detected in M. barkeri. Three-way comparison of these genomes reveals differing mechanisms for the accrual of changes. Elongation of the relatively large M. acetivorans genome is the result of uniformly distributed multiple gene scale insertions and duplications, while the M. barkeri genome is characterized by localized inversions associated with the loss of gene content. In contrast, the short M. mazei genome most closely approximates the putative ancestral organizational state of these species.

Ferredoxins↗

PubMed1997

Complete genome sequence of Methanobacterium thermoautotrophicum deltaH: functional analysis and comparative genomics.

The complete 1,751,377-bp sequence of the genome of the thermophilic archaeon Methanobacterium thermoautotrophicum deltaH has been determined by a whole-genome shotgun sequencing approach. A total of 1,855 open reading frames (ORFs) have been identified that appear to encode polypeptides, 844 (46%) of which have been assigned putative functions based on their similarities to database sequences with assigned functions. A total of 514 (28%) of the ORF-encoded polypeptides are related to sequences with unknown functions, and 496 (27%) have little or no homology to sequences in public databases. Comparisons with Eucarya-, Bacteria-, and Archaea-specific databases reveal that 1,013 of the putative gene products (54%) are most similar to polypeptide sequences described previously for other organisms in the domain Archaea. Comparisons with the Methanococcus jannaschii genome data underline the extensive divergence that has occurred between these two methanogens; only 352 (19%) of M. thermoautotrophicum ORFs encode sequences that are >50% identical to M. jannaschii polypeptides, and there is little conservation in the relative locations of orthologous genes. When the M. thermoautotrophicum ORFs are compared to sequences from only the eucaryal and bacterial domains, 786 (42%) are more similar to bacterial sequences and 241 (13%) are more similar to eucaryal sequences. The bacterial domain-like gene products include the majority of those predicted to be involved in cofactor and small molecule biosyntheses, intermediary metabolism, transport, nitrogen fixation, regulatory functions, and interactions with the environment. Most proteins predicted to be involved in DNA metabolism, transcription, and translation are more similar to eucaryal sequences. Gene structure and organization have features that are typical of the Bacteria, including genes that encode polypeptides closely related to eucaryal proteins. There are 24 polypeptides that could form two-component sensor kinase-response regulator systems and homologs of the bacterial Hsp70-response proteins DnaK and DnaJ, which are notably absent in M. jannaschii. DNA replication initiation and chromosome packaging in M. thermoautotrophicum are predicted to have eucaryal features, based on the presence of two Cdc6 homologs and three histones; however, the presence of an ftsZ gene indicates a bacterial type of cell division initiation. The DNA polymerases include an X-family repair type and an unusual archaeal B type formed by two separate polypeptides. The DNA-dependent RNA polymerase (RNAP) subunits A', A", B', B" and H are encoded in a typical archaeal RNAP operon, although a second A' subunit-encoding gene is present at a remote location. There are two rRNA operons, and 39 tRNA genes are dispersed around the genome, although most of these occur in clusters. Three of the tRNA genes have introns, including the tRNAPro (GGG) gene, which contains a second intron at an unprecedented location. There is no selenocysteinyl-tRNA gene nor evidence for classically organized IS elements, prophages, or plasmids. The genome contains one intein and two extended repeats (3.6 and 8.6 kb) that are members of a family with 18 representatives in the M. jannaschii genome.

Anaerobiosis↗

PubMed2003

Genome-scale analysis of the uses of the Escherichia coli genome: model-driven analysis of heterogeneous data sets.

The recent availability of heterogeneous high-throughput data types has increased the need for scalable in silico methods with which to integrate data related to the processes of regulation, protein synthesis, and metabolism. A sequence-based framework for modeling transcription and translation in prokaryotes has been established and has been extended to study the expression state of the entire Escherichia coli genome. The resulting in silico analysis of the expression state highlighted three facets of gene expression in E. coli: (i) the metabolic resources required for genome expression and protein synthesis were found to be relatively invariant under the conditions tested; (ii) effective promoter strengths were estimated at the genome scale by using global mRNA abundance and half-life data, revealing genes subject to regulation under the experimental conditions tested; and (iii) large-scale genome location-dependent expression patterns with approximately 600-kb periodicity were detected in the E. coli genome based on the 49 expression data sets analyzed. These results support the notion that a structured model-driven analysis of expression data yields additional information that can be subjected to commonly used statistical analyses. The integration of heterogeneous genome-scale data (i.e., sequence, expression data, and mRNA half-life data) is readily achieved in the context of an in silico model.

Bacterial Proteins↗

PubMed2005

The complete genome sequence of J virus reveals a unique genome structure in the family Paramyxoviridae.

J virus (J-V) was isolated from feral mice (Mus musculus) trapped in Queensland, Australia, during the early 1970s. Although studies undertaken at the time revealed that J-V was a new paramyxovirus, it remained unclassified beyond the family level. The complete genome sequence of J-V has now been determined, revealing a genome structure unique within the family Paramyxoviridae. At 18,954 nucleotides (nt), the J-V genome is the largest paramyxovirus genome sequenced to date, containing eight genes in the order 3'-N-P/V/C-M-F-SH-TM-G-L-5'. The two genes located between the fusion (F) and attachment (G) protein genes, which have been named the small hydrophobic (SH) protein gene and the transmembrane (TM) protein gene, encode putative proteins of 69 and 258 amino acids, respectively. The 4,401-nt J-V G gene, much larger than other paramyxovirus attachment protein genes sequenced to date, encodes a putative attachment protein of 709 amino acids and distally contains a second open reading frame (ORF) of 2,115 nt, referred to as ORF-X. Taken together, these novel features represent the most significant divergence to date from the common six-gene genome structure of Paramyxovirinae. Although genome analysis has confirmed that J-V can be classified as a member of the subfamily Paramyxovirinae, it cannot be assigned to any of the five existing genera within this subfamily. Interestingly, a recently isolated paramyxovirus appears to be closely related to J-V, and preliminary phylogenetic analyses based on putative matrix protein sequences indicate that these two viruses will likely represent a new genus within the subfamily Paramyxovirinae.

Amino Acid Sequence↗

PubMed2005

Complete genome sequence of the grouper iridovirus and comparison of genomic organization with those of other iridoviruses.

The complete DNA sequence of grouper iridovirus (GIV) was determined using a whole-genome shotgun approach on virion DNA. The circular form genome was 139,793 bp in length with a 49% G + C content. It contained 120 predicted open reading frames (ORFs) with coding capacities ranging from 62 to 1,268 amino acids. A total of 21% (25 of 120) of GIV ORFs are conserved in the other five sequenced iridovirus genomes, including DNA replication, transcription, nucleotide metabolism, protein modification, viral structure, and virus-host interaction genes. The whole-genome nucleotide pairwise comparison showed that GIV virus was partially colinear with counterparts of previously sequenced ranaviruses (ATV and TFV). Besides, sequence analysis revealed that GIV possesses several unique features which are different from those of other complete sequenced iridovirus genomes: (i) GIV is the first ranavirus-like virus which has been sequenced completely and which infects fish other than amphibians, (ii) GIV is the only vertebrate iridovirus without CpG sequence methylation and lacking DNA methyltransferase, (iii) GIV contains a purine nucleoside phosphorylase gene which is not found in other iridoviruses or in any other viruses, (iv) GIV contains 17 sets of repeat sequence, with basic unit sizes ranging from 9 to 63 bp, dispersed throughout the whole genome. These distinctive features of GIV further extend our understanding of molecular events taking place between ranavirus and its hosts and the iridovirus evolution.

Animals↗

PubMed2006

Mitochondrial genomes of Vanhornia eucnemidarum (Apocrita: Vanhorniidae) and Primeuchroeus spp. (Aculeata: Chrysididae): Evidence of rearranged mitochondrial genomes within the Apocrita (Insecta: Hymenoptera).

We sequenced most of the mitochondrial (mt) genomes of 2 apocritan taxa: Vanhornia eucnemidarum and Primeuchroeus spp. These mt genomes have similar nucleotide composition and codon usage to those of mt genomes reported for other Hymenoptera, with a total A + T content of 80.1% and 78.2%, respectively. Gene content corresponds to that of other metazoan mt genomes, but gene organization is not conserved. There are a total of 6 tRNA genes rearranged in V. eucnemidarum and 9 in Primeuchroeus spp. Additionally, several noncoding regions were found in the mt genome of V. eucnemidarum, as well as evidence of a sustained gene duplication involving 3 tRNA genes. We also report an inversion of the large and small ribosomal RNA genes in Primeuchroeus spp. mt genome. However, none of the rearrangements reported are phylogenetically informative with respect to the current taxon sample.

Animals↗

PubMed2004

Use of whole genome amplification and comparative genomic hybridisation to detect chromosomal copy number alterations in cell line material and tumour tissue.

We have established that whole genome amplification (WGA), in conjunction with genomic DNA array comparative genomic hybridisation (gaCGH) allows for the identification of genome-wide copy number abnormalities (CNAs) in DNA extracted from both cell line and patient material. To determine the fidelity and reproducibility of WGA to detect copy number imbalances using gaCGH, well characterized cell line genomic DNA was analysed. The gaCGH data obtained from non-amplified DNA and amplified DNA for the neuroblastoma cell line NUB7 and a paediatric medulloblastoma patient was almost identical. In addition, laser capture microdissection (LCM) of prostate tumour cells and subsequent WGA allowed for the detection of a number of CNAs that may not have been identified if DNA had been extracted in bulk from heterogeneous tissue. The results presented here demonstrate the use of WGA for generating sufficient DNA for gaCGH analysis without the introduction of significant sequence representation bias. The combination of amplification and gaCGH using DNA extracted from archival patient material has the potential for permitting the studying of DNA from small cancerous or pre-cancerous foci, which may help to identify potential genomic markers for early diagnosis.

Cell Line↗

PubMed2004

SeeGH--a software tool for visualization of whole genome array comparative genomic hybridization data.

BACKGROUND: Array comparative genomic hybridization (CGH) is a technique which detects copy number differences in DNA segments. Complete sequencing of the human genome and the development of an array representing a tiling set of tens of thousands of DNA segments spanning the entire human genome has made high resolution copy number analysis throughout the genome possible. Since array CGH provides signal ratio for each DNA segment, visualization would require the reassembly of individual data points into chromosome profiles. RESULTS: We have developed a visualization tool for displaying whole genome array CGH data in the context of chromosomal location. SeeGH is an application that translates spot signal ratio data from array CGH experiments to displays of high resolution chromosome profiles. Data is imported from a simple tab delimited text file obtained from standard microarray image analysis software. SeeGH processes the signal ratio data and graphically displays it in a conventional CGH karyotype diagram with the added features of magnification and DNA segment annotation. In this process, SeeGH imports the data into a database, calculates the average ratio and standard deviation for each replicate spot, and links them to chromosome regions for graphical display. Once the data is displayed, users have the option of hiding or flagging DNA segments based on user defined criteria, and retrieve annotation information such as clone name, NCBI sequence accession number, ratio, base pair position on the chromosome, and standard deviation. CONCLUSIONS: SeeGH represents a novel software tool used to view and analyze array CGH data. The software gives users the ability to view the data in an overall genomic view as well as magnify specific chromosomal regions facilitating the precise localization of genetic alterations. SeeGH is easily installed and runs on Microsoft Windows 2000 or later environments.

Chromosome Mapping↗

PubMed2006

A novel statistical method to estimate the effective SNP size in vertebrate genomes and categorized genomic regions.

BACKGROUND: The local environment of single nucleotide polymorphisms (SNPs) contains abundant genetic information for the study of mechanisms of mutation, genome evolution, and causes of diseases. Recent studies revealed that neighboring-nucleotide biases on SNPs were strong and the genome-wide bias patterns could be represented by a small subset of the total SNPs. It remains unsolved for the estimation of the effective SNP size, the number of SNPs that are sufficient to represent the bias patterns observed from the whole SNP data. RESULTS: To estimate the effective SNP size, we developed a novel statistical method, SNPKS, which considers both the statistical and biological significances. SNPKS consists of two major steps: to obtain an initial effective size by the Kolmogorov-Smirnov test (KS test) and to find an intermediate effective size by interval evaluation. The SNPKS algorithm was implemented in computer programs and applied to the real SNP data. The effective SNP size was estimated to be 38,200, 39,300, 38,000, and 38,700 in the human, chimpanzee, dog, and mouse genomes, respectively, and 39,100, 39,600, 39,200, and 42,200 in human intergenic, genic, intronic, and CpG island regions, respectively. CONCLUSION: SNPKS is the first statistical method to estimate the effective SNP size. It runs efficiently and greatly outperforms the algorithm implemented in SNPNB. The application of SNPKS to the real SNP data revealed the similar small effective SNP size (38,000 - 42,200) in the human, chimpanzee, dog, and mouse genomes as well as in human genomic regions. The findings suggest strong influence of genetic factors across vertebrate genomes.

Algorithms↗

PubMed2006

Comparison of chromosomal and array-based comparative genomic hybridization for the detection of genomic imbalances in primary prostate carcinomas.

BACKGROUND: In order to gain new insights into the molecular mechanisms involved in prostate cancer, we performed array-based comparative genomic hybridization (aCGH) on a series of 46 primary prostate carcinomas using a 1 Mbp whole-genome coverage platform. As chromosomal comparative genomic hybridization (cCGH) data was available for these samples, we compared the sensitivity and overall concordance of the two methodologies, and used the combined information to infer the best of three different aCGH scoring approaches. RESULTS: Our data demonstrate that the reliability of aCGH in the analysis of primary prostate carcinomas depends to some extent on the scoring approach used, with the breakpoint estimation method being the most sensitive and reliable. The pattern of copy number changes detected by aCGH was concordant with that of cCGH, but the higher resolution technique detected 2.7 times more aberrations and 15.2% more carcinomas with genomic imbalances. We additionally show that several aberrations were consistently overlooked using cCGH, such as small deletions at 5q, 6q, 12p, and 17p. The latter were validated by fluorescence in situ hybridization targeting TP53, although only one carcinoma harbored a point mutation in this gene. Strikingly, homozygous deletions at 10q23.31, encompassing the PTEN locus, were seen in 58% of the cases with 10q loss. CONCLUSION: We conclude that aCGH can significantly improve the detection of genomic aberrations in cancer cells as compared to previously established whole-genome methodologies, although contamination with normal cells may influence the sensitivity and specificity of some scoring approaches. Our work delineated recurrent copy number changes and revealed novel amplified loci and frequent homozygous deletions in primary prostate carcinomas, which may guide future work aimed at identifying the relevant target genes. In particular, biallelic loss seems to be a frequent mechanism of inactivation of the PTEN gene in prostate carcinogenesis.

Chromosome Aberrations↗

PubMed2002

Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster euchromatic genome sequence.

BACKGROUND: The Drosophila melanogaster genome was the first metazoan genome to have been sequenced by the whole-genome shotgun (WGS) method. Two issues relating to this achievement were widely debated in the genomics community: how correct is the sequence with respect to base-pair (bp) accuracy and frequency of assembly errors? And, how difficult is it to bring a WGS sequence to the accepted standard for finished sequence? We are now in a position to answer these questions. RESULTS: Our finishing process was designed to close gaps, improve sequence quality and validate the assembly. Sequence traces derived from the WGS and draft sequencing of individual bacterial artificial chromosomes (BACs) were assembled into BAC-sized segments. These segments were brought to high quality, and then joined to constitute the sequence of each chromosome arm. Overall assembly was verified by comparison to a physical map of fingerprinted BAC clones. In the current version of the 116.9 Mb euchromatic genome, called Release 3, the six euchromatic chromosome arms are represented by 13 scaffolds with a total of 37 sequence gaps. We compared Release 3 to Release 2; in autosomal regions of unique sequence, the error rate of Release 2 was one in 20,000 bp. CONCLUSIONS: The WGS strategy can efficiently produce a high-quality sequence of a metazoan genome while generating the reagents required for sequence finishing. However, the initial method of repeat assembly was flawed. The sequence we report here, Release 3, is a reliable resource for molecular genetic experimentation and computational analysis.

Animals↗

PubMed2002

Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome.

BACKGROUND: It is widely accepted that comparative sequence data can aid the functional annotation of genome sequences; however, the most informative species and features of genome evolution for comparison remain to be determined. RESULTS: We analyzed conservation in eight genomic regions (apterous, even-skipped, fushi tarazu, twist, and Rhodopsins 1, 2, 3 and 4) from four Drosophila species (D. erecta, D. pseudoobscura, D. willistoni, and D. littoralis) covering more than 500 kb of the D. melanogaster genome. All D. melanogaster genes (and 78-82% of coding exons) identified in divergent species such as D. pseudoobscura show evidence of functional constraint. Addition of a third species can reveal functional constraint in otherwise non-significant pairwise exon comparisons. Microsynteny is largely conserved, with rearrangement breakpoints, novel transposable element insertions, and gene transpositions occurring in similar numbers. Rates of amino-acid substitution are higher in uncharacterized genes relative to genes that have previously been studied. Conserved non-coding sequences (CNCSs) tend to be spatially clustered with conserved spacing between CNCSs, and clusters of CNCSs can be used to predict enhancer sequences. CONCLUSIONS: Our results provide the basis for choosing species whose genome sequences would be most useful in aiding the functional annotation of coding and cis-regulatory sequences in Drosophila. Furthermore, this work shows how decoding the spatial organization of conserved sequences, such as the clustering of CNCSs, can complement efforts to annotate eukaryotic genomes on the basis of sequence conservation alone.

Animals↗

PubMed2003

Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence.

BACKGROUND: Previous studies have suggested that recent segmental duplications, which are often involved in chromosome rearrangements underlying genomic disease, account for some 5% of the human genome. We have developed rapid computational heuristics based on BLAST analysis to detect segmental duplications, as well as regions containing potential sequence misassignments in the human genome assemblies. RESULTS: Our analysis of the June 2002 public human genome assembly revealed that 107.4 of 3,043.1 megabases (Mb) (3.53%) of sequence contained segmental duplications, each with size equal or more than 5 kb and 90% identity. We have also detected that 38.9 Mb (1.28%) of sequence within this assembly is likely to be involved in sequence misassignment errors. Furthermore, we have identified a significant subset (199,965 of 2,327,473 or 8.6%) of single-nucleotide polymorphisms (SNPs) in the public databases that are not true SNPs but are potential paralogous sequence variants. CONCLUSION: Using two distinct computational approaches, we have identified most of the sequences in the human genome that have undergone recent segmental duplications. Near-identical segmental duplications present a major challenge to the completion of the human genome sequence. Potential sequence misassignments detected in this study would require additional efforts to resolve.

Artifacts↗

PubMed2006

Detecting copy number variation in the human genome using comparative genomic hybridization.

Among human beings, it was once estimated that our genomes were 99.9% genetically identical. While this high level of genetic similarity helps to define us as a species, it is our genetic variation that contributes to our phenotypic diversity. As genomic technologies evolve to provide genome-wide analyses at higher resolution, we are beginning to appreciate that the human genome has a lot more variation than was once thought. Array-based comparative genomic hybridization (CGH) is one of these technologies that has recently revealed a newly appreciated type of genetic variation: copy number variation, in which thousands of regions of the human genome are now known to be variable in number between individuals. Some of these copy number variable regions have already been shown to predispose to certain common diseases, and others may ultimately have a significant impact on how each of us reacts to certain foods (e.g., allergic reactions), medications (e.g., pharmacogenomics), microscopic infections (i.e., immunity), and other aspects of our ever-changing environment.

Gene Dosage↗