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- Hooper, Sean D, et al.
(author)
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Detection of genes with atypical nucleotide sequence in microbial genomes
- 2002
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In: Journal of Molecular Evolution. - : Springer Science and Business Media LLC. - 0022-2844 .- 1432-1432. ; 54:3, s. 365-375
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Journal article (peer-reviewed)abstract
- Along the gene, nucleotides in various codon positions tend to exert a slight but observable influence on the nucleotide choice at neighboring positions. Such context biases are different in different organisms and can be used as genomic signatures. In this paper, we will focus specifically on the dinucleotide composed of a third codon position nucleotide and its succeeding first position nucleotide. Using the 16 possible dinucleotide combinations, we calculate how well individual genes conform to the observed mean dinucleotide frequencies of an entire genome, forming a distance measure for each gene. It is found that genes from different genomes can be separated with a high degree of accuracy, according to these distance values. In particular, we address the problem of recent horizontal gene transfer, and how imported genes may be evaluated by their poor assimilation to the host's context biases. By concentrating on the third- and succeeding first position nucleotides, we eliminate most spurious contributions from codon usage and amino-acid requirements, focusing mainly on mutational effects. Since imported genes are expected to converge only gradually to genomic signatures, it is possible to question whether a gene present in only one of two closely related organisms has been imported into one organism or deleted in the other. Striking correlations between the proposed distance measure and poor homology are observed when Escherichia coli genes are compared to Salmonella typhi, indicating that sets of outlier genes in E. coli may contain a high number of genes that have been imported into E. coli, and not deleted in S. typhi.
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| 4. |
- Hooper, Sean D, et al.
(author)
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Gene Import or Deletion : A Study of the Different Genes in Escherichia coli Strains K12 and O157:H7
- 2002
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In: Journal of Molecular Evolution. - : Springer Science and Business Media LLC. - 0022-2844 .- 1432-1432. ; 55:6, s. 734-744
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Journal article (peer-reviewed)abstract
- By comparing two strains of Escherichia coli (K12 and O157:H7) with an outgroup of Salmonella and Klebsiella species and analyzing the sets of genes which are present or absent in either of the three groups, we study the gene history of K12, in particular, since the respective divergences of these bacteria. Furthermore, by using a compositional method based on context bias, we evaluate not only recently imported genes but also deleted genes. In addition, we examine recent gene duplications in the two E. coli strains. It is found that turnover of DNA is high in E. coli and, more importantly, that turnover is highest for genes of low GC content. Although levels of import are high, most of the imported genes seem to be "junk" or have poorly understood functions. Nevertheless, selected genes do persist, and may even define some E. coli strains as pathogenic. Our results support the conclusion that some of the pathogenic islands in O157:H7 are likely to have been imported in recent time.
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| 5. |
- Hooper, Sean D., et al.
(author)
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Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder
- 2012
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13, s. 123-
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Journal article (peer-reviewed)abstract
- Background: Tourette Syndrome (TS) is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood. Methods: Using cytogenetics and FISH analysis, we identified an apparently balanced t(6,22)(q16.2;p13) in a male patient with TS and obsessive-compulsive disorder (OCD). In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband. Results: Sequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32) and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband's mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome. Conclusions: We conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.
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| 6. |
- Hooper, Sean D, et al.
(author)
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Gradients in nucleotide and codon usage along Escherichia coli genes
- 2000
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 28:18, s. 3517-3523
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Journal article (peer-reviewed)abstract
- The usage of codons and nucleotide combinations varies along genes and systematic variation causes gradients in usage. We have studied such gradients of nucleotides and nucleotide combinations and their immediate context in Escherichia coli. To distinguish mutational and selectional effects, the genes were subdivided into three groups with different codon usage bias and the gradients of nucleotide usage were studied in each group. Some combinations that can be associated with a propensity for processivity errors show strong negative gradients that become weaker in genes with low codon bias, consistent with a selection on translational efficiency. One of the strongest gradients is for third position G, which shows a pervasive positive gradient in usage in most contexts of surrounding bases.
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| 9. |
- Jiao, Xiang, et al.
(author)
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Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing
- 2013
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 14
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Journal article (peer-reviewed)abstract
- Background: Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. Results: We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. Conclusions: Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.
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| 10. |
- Jiao, Xiang, et al.
(author)
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Structural Alterations from Multiple Displacement Amplification of a Human Genome Revealed by Mate-Pair Sequencing
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7, s. e22250-
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Journal article (peer-reviewed)abstract
- Comprehensive identification of the acquired mutations that cause common cancers will require genomic analyses of large sets of tumor samples. Typically, the tissue material available from tumor specimens is limited, which creates a demand for accurate template amplification. We therefore evaluated whether phi29-mediated whole genome amplification introduces false positive structural mutations by massive mate-pair sequencing of a normal human genome before and after such amplification. Multiple displacement amplification led to a decrease in clone coverage and an increase by two orders of magnitude in the prevalence of inversions, but did not increase the prevalence of translocations. While multiple strand displacement amplification may find uses in translocation analyses, it is likely that alternative amplification strategies need to be developed to meet the demands of cancer genomics.
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