publication . Thesis . 2017

Within genome variation of germ-line and somatic mutation

Smith, Thomas C A;
Open Access English
  • Published: 05 May 2017
  • Country: United Kingdom
Abstract
Variation in the mutation rate along the human genome, if not properly understood and accounted\ud for, has the potential to confound evolutionary studies, produce spurious driver candidates in cancer\ud studies, and hinder the diagnostics aimed at understanding the etiologies of genetic diseases.\ud \ud In this thesis I consider mutation rate variation in both the germ-line and somatic tissues, at varying\ud scales. In the germ-line, the major advance of this thesis over previous works is use of direct\ud methods to analyse the magnitude, scale and determinants of mutation rate variation. This has\ud enabled us to tease apart the evolutionary and mutational for...
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free text keywords: QH0426
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71 references, page 1 of 5

Smith, J.D. and Turner, E.H., 2012. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 485(7397), pp.246-250.

Ozeri-Galai, E., Bester, A.C. & Kerem, B., 2012. The complex basis underlying common fragile site instability in cancer. Trends in Genetics, 28(6), pp.295-302. [OpenAIRE]

Panchin, A.Y., Makeev, V.J. & Medvedeva, Y.A., 2016. Preservation of methylated CpG dinucleotides in human CpG islands. Biology direct, 11(1), p.11. [OpenAIRE]

Paten, B., Herrero, J., Beal, K., Fitzgerald, S. and Birney, E., 2008. Enredo and Pecan: genomewide mammalian consistency-based multiple alignment with paralogs. Genome research, 18(11), pp.1814-1828. [OpenAIRE]

Paten, B., Herrero, J., Beal, K. and Birney, E., 2009. Sequence progressive alignment, a framework for practical large-scale probabilistic consistency alignment. Bioinformatics, 25(3), pp.295- 301.

Petermann, E., Orta, M.L., Issaeva, N., Schultz, N. and Helleday, T., 2010. Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Molecular cell, 37(4), pp.492-502. [OpenAIRE]

Pink, C.J. & Hurst, L.D., 2010. Timing of replication is a determinant of neutral substitution rates but does not explain slow y chromosome evolution in rodents. Molecular Biology and Evolution, 27(5), pp.1077-1086.

Pinto, Y., Gabay, O., Arbiza, L., Sams, A.J., Keinan, A. and Levanon, E.Y., 2016. Clustered mutations in hominid genome evolution are consistent with APOBEC3G enzymatic activity. Genome research, 26(5), pp.579-587.

Poduri, A., Evrony, G.D., Cai, X., Elhosary, P.C., Beroukhim, R., Lehtinen, M.K., Hills, L.B., Heinzen, E.L., Hill, A., Hill, R.S. and Barry, B.J., 2012. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron, 74(1), pp.41-48.

Poduri, A., Evrony, G.D., Cai, X. and Walsh, C.A., 2013. Somatic mutation, genomic variation, and neurological disease. Science, 341(6141), p.1237758. [OpenAIRE]

Polak, P. & Arndt, P.F., 2008. Transcription induces strand-specific mutations at the 5??? end of human genes. Genome Research, 18(8), pp.1216-1223.

Polak, P., Karlić, R., Koren, A., Thurman, R., Sandstrom, R., Lawrence, M.S., Reynolds, A., Rynes, E., Vlahoviček, K., Stamatoyannopoulos, J.A. and Sunyaev, S.R., 2015. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature, 518(7539), pp.360- 364. [OpenAIRE]

Prendergast, J.G.D. et al., 2007. Chromatin structure and evolution in the human genome. BMC evolutionary biology, 7, p.72.

Price, E.A., Price, K., Kolkiewicz, K., Hack, S., Reddy, M.A., Hungerford, J.L., Kingston, J.E. and Onadim, Z., 2013. Spectrum of RB1 mutations identified in 403 retinoblastoma patients. Journal of medical genetics, pp.jmedgenet-2013. [OpenAIRE]

Quail, M.A., Kozarewa I., Smith F., Scally A., Stephens P.J., Durbin R., Swerdlow H., Turner D.J. 2008. A large genome center's improvements to the Illumina sequencing system. Nature methods 5:1005-10.

71 references, page 1 of 5
Abstract
Variation in the mutation rate along the human genome, if not properly understood and accounted\ud for, has the potential to confound evolutionary studies, produce spurious driver candidates in cancer\ud studies, and hinder the diagnostics aimed at understanding the etiologies of genetic diseases.\ud \ud In this thesis I consider mutation rate variation in both the germ-line and somatic tissues, at varying\ud scales. In the germ-line, the major advance of this thesis over previous works is use of direct\ud methods to analyse the magnitude, scale and determinants of mutation rate variation. This has\ud enabled us to tease apart the evolutionary and mutational for...
Subjects
free text keywords: QH0426
Related Organizations
Download from
71 references, page 1 of 5

Smith, J.D. and Turner, E.H., 2012. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 485(7397), pp.246-250.

Ozeri-Galai, E., Bester, A.C. & Kerem, B., 2012. The complex basis underlying common fragile site instability in cancer. Trends in Genetics, 28(6), pp.295-302. [OpenAIRE]

Panchin, A.Y., Makeev, V.J. & Medvedeva, Y.A., 2016. Preservation of methylated CpG dinucleotides in human CpG islands. Biology direct, 11(1), p.11. [OpenAIRE]

Paten, B., Herrero, J., Beal, K., Fitzgerald, S. and Birney, E., 2008. Enredo and Pecan: genomewide mammalian consistency-based multiple alignment with paralogs. Genome research, 18(11), pp.1814-1828. [OpenAIRE]

Paten, B., Herrero, J., Beal, K. and Birney, E., 2009. Sequence progressive alignment, a framework for practical large-scale probabilistic consistency alignment. Bioinformatics, 25(3), pp.295- 301.

Petermann, E., Orta, M.L., Issaeva, N., Schultz, N. and Helleday, T., 2010. Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Molecular cell, 37(4), pp.492-502. [OpenAIRE]

Pink, C.J. & Hurst, L.D., 2010. Timing of replication is a determinant of neutral substitution rates but does not explain slow y chromosome evolution in rodents. Molecular Biology and Evolution, 27(5), pp.1077-1086.

Pinto, Y., Gabay, O., Arbiza, L., Sams, A.J., Keinan, A. and Levanon, E.Y., 2016. Clustered mutations in hominid genome evolution are consistent with APOBEC3G enzymatic activity. Genome research, 26(5), pp.579-587.

Poduri, A., Evrony, G.D., Cai, X., Elhosary, P.C., Beroukhim, R., Lehtinen, M.K., Hills, L.B., Heinzen, E.L., Hill, A., Hill, R.S. and Barry, B.J., 2012. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron, 74(1), pp.41-48.

Poduri, A., Evrony, G.D., Cai, X. and Walsh, C.A., 2013. Somatic mutation, genomic variation, and neurological disease. Science, 341(6141), p.1237758. [OpenAIRE]

Polak, P. & Arndt, P.F., 2008. Transcription induces strand-specific mutations at the 5??? end of human genes. Genome Research, 18(8), pp.1216-1223.

Polak, P., Karlić, R., Koren, A., Thurman, R., Sandstrom, R., Lawrence, M.S., Reynolds, A., Rynes, E., Vlahoviček, K., Stamatoyannopoulos, J.A. and Sunyaev, S.R., 2015. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature, 518(7539), pp.360- 364. [OpenAIRE]

Prendergast, J.G.D. et al., 2007. Chromatin structure and evolution in the human genome. BMC evolutionary biology, 7, p.72.

Price, E.A., Price, K., Kolkiewicz, K., Hack, S., Reddy, M.A., Hungerford, J.L., Kingston, J.E. and Onadim, Z., 2013. Spectrum of RB1 mutations identified in 403 retinoblastoma patients. Journal of medical genetics, pp.jmedgenet-2013. [OpenAIRE]

Quail, M.A., Kozarewa I., Smith F., Scally A., Stephens P.J., Durbin R., Swerdlow H., Turner D.J. 2008. A large genome center's improvements to the Illumina sequencing system. Nature methods 5:1005-10.

71 references, page 1 of 5
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