Use of somatic mutations to quantify random contributions to mouse development

Zhou, Wenyu; Tan, Yunbing; Anderson, Donovan J.; Crist, Eva; Ruohola‐Baker, Hannele; Salipante, Stephen J.; Horwitz, Marshall S.

doi:10.1186/1471-2164-14-39

Cited by 13 publications

(9 citation statements)

References 64 publications

(73 reference statements)

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“…This may be a reasonable assumption, although somatic mutations have been demonstrated in genome-wide surveys and are known to accumulate with age in mammals [328][329][330], but it is unclear how much they may contribute to normal phenotypic variation. For plants, where ample opportunity for somatic mutation exists and extensive research on genetic mosaicism has been conducted, Herrera [262] reviewed the available evidence and concluded that such genetic variation is only rarely responsible for appreciable portion of within-individual variation.…”

Section: The Central Argument: Fluctuating Asymmetry As a Measure Of mentioning

confidence: 99%

Analyzing Fluctuating Asymmetry with Geometric Morphometrics: Concepts, Methods, and Applications

2015

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Approximately two decades after the first pioneering analyses, the study of shape asymmetry with the methods of geometric morphometrics has matured and is a burgeoning field. New technology for data collection and new methods and software for analysis are widely available and have led to numerous applications in plants and animals, including humans. This review summarizes the concepts and morphometric methods for studying asymmetry of shape and size. After a summary of mathematical and biological concepts of symmetry and asymmetry, a section follows that explains the methods of geometric morphometrics and how they can be used to analyze asymmetry of biological structures. Geometric morphometric analyses not only tell how much asymmetry there is, but also provide information about the patterns of covariation in the structure under study. Such patterns of covariation in fluctuating asymmetry can provide valuable insight about the developmental basis of morphological integration, and have become important tools for evolutionary developmental biology. The genetic basis of fluctuating asymmetry has been studied from empirical and theoretical viewpoints, but serious challenges remain in this area. There are many promising areas for further research that are only little explored at present.

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Section: The Central Argument: Fluctuating Asymmetry As a Measure Of mentioning

confidence: 99%

Analyzing Fluctuating Asymmetry with Geometric Morphometrics: Concepts, Methods, and Applications

2015

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“…Somatic mutations in normal cells from multicellular organisms can provide insights into the origins and past experiences of each cell 4 . The developmental lineages of individual cells may be reconstructed, as previously explored in studies using insertion/deletion mutations at short tandem repeats 1,5-11 (Supplementary Discussion A). Complete reconstruction of the bifurcating cell division tree requires at least one somatic mutation in the two daughter cells arising from each cell division.…”

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confidence: 99%

Genome sequencing of normal cells reveals developmental lineages and mutational processes

Behjati

Huch

Boxtel

et al. 2014

Nature

334

263

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The somatic mutations present in the genome of a cell have been accumulated over the lifetime of a multicellular organism. These mutations can provide insights into the developmental lineage tree 1 , the number of divisions each cell has undergone and the mutational processes that have been operative 2 . Here, we conducted whole genome sequencing of clonal lines 3 derived from multiple tissues of healthy mice. Using somatic base substitutions, we reconstructed the early cell divisions of each animal demonstrating the contributions of embryonic cells to adult tissues. Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible.

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“…Analysis of poly-G repeats has successfully been used to study phylogenetic relationships between single cells in mouse development (22)(23)(24) and has been adapted for detecting preneoplastic clonal expansions in ulcerative colitis patients (25).…”

mentioning

confidence: 99%

Hypermutable DNA chronicles the evolution of human colon cancer

Naxerova

Brachtel

Salk

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Intratumor genetic heterogeneity reflects the evolutionary history of a cancer and is thought to influence treatment outcomes. Here we report that a simple PCR-based assay interrogating somatic variation in hypermutable polyguanine (poly-G) repeats can provide a rapid and reliable assessment of mitotic history and clonal architecture in human cancer. We use poly-G repeat genotyping to study the evolution of colon carcinoma. In a cohort of 22 patients, we detect poly-G variants in 91% of tumors. Patient age is positively correlated with somatic mutation frequency, suggesting that some poly-G variants accumulate before the onset of carcinogenesis during normal division in colonic stem cells. Poorly differentiated tumors have fewer mutations than well-differentiated tumors, possibly indicating a shorter mitotic history of the founder cell in these cancers. We generate poly-G mutation profiles of spatially separated samples from primary carcinomas and matched metastases to build well-supported phylogenetic trees that illuminate individual patients' path of metastatic progression. Our results show varying degrees of intratumor heterogeneity among patients. Finally, we show that poly-G mutations can be found in other cancers than colon carcinoma. Our approach can generate reliable maps of intratumor heterogeneity in large numbers of patients with minimal time and cost expenditure.lineage tracing | microsatellites | tumor phylogenetics H uman cancers are composed of a continually evolving population of genetically and phenotypically divergent cells (1). This reservoir of diversity feeds the natural selection process that fundamentally drives disease progression through acquisition of metastatic properties and emergence of therapy-resistant clones (2-4). In recent years, characterization of intratumor heterogeneity has received increased attention as advanced sequencing technologies have enabled more detailed analysis of tumor cell populations (5-8).Depending on the context, the term "intratumor heterogeneity" refers either to differences between cells that coexist in one localized tumor region or to variation in clonal composition between spatially separated parts, most notably between a primary tumor and its metastases (in the latter case, "intracancer heterogeneity" is a more appropriate terminology). The extent of genetic divergence between primary and metastatic tumors (and the history of dissemination encoded therein) is beginning to be investigated, but relatively few patient data are currently available. The canonical "linear progression" model of metastasis states that a genetically advanced cell metastasizes late in primary tumor development (9-11). This aggressive clone generates new metastases in a so-called "metastasis shower" (12). Linear progression predicts that metastases will be genetically similar to the primary tumor and to each other. The alternative "parallel progression" model (9) posits that metastasis occurs early in tumor evolution and consequently expects metastases to be substantially differe...

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Use of somatic mutations to quantify random contributions to mouse development

Cited by 13 publications

References 64 publications

Analyzing Fluctuating Asymmetry with Geometric Morphometrics: Concepts, Methods, and Applications

Analyzing Fluctuating Asymmetry with Geometric Morphometrics: Concepts, Methods, and Applications

Genome sequencing of normal cells reveals developmental lineages and mutational processes

Hypermutable DNA chronicles the evolution of human colon cancer

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