Somatic point mutations occurring early in development: a monozygotic twin study

  title={Somatic point mutations occurring early in development: a monozygotic twin study},
  author={Rui Li and Alexandre Montpetit and Maryl{\`e}ne Rousseau and Si-Yu Wu and Celia M. T. Greenwood and Tim D. Spector and Michael N. Pollak and Constantin Polychronakos and J. Brent Richards},
  journal={Journal of Medical Genetics},
  pages={28 - 34}
The identification of somatic driver mutations in cancer has enabled therapeutic advances by identifying drug targets critical to disease causation. However, such genomic discoveries in oncology have not translated into advances for non-cancerous disease since point mutations in a single cell would be unlikely to cause non-malignant disease. An exception to this would occur if the mutation happened early enough in development to be present in a large percentage of a tissue's cellular population… 

Deep sequencing reveals variations in somatic cell mosaic mutations between monozygotic twins with discordant psychiatric disease

The results suggest that deep sequencing analysis would be an adequate method to detect discordant mutations in candidate genes responsible for heritable diseases.

A characterization of postzygotic mutations identified in monozygotic twins

This research shows that somatic mosaicism can be detected in monozygotic twin pairs by using allelic ratios calculated from DNA sequence data and that the mutations which are found by this approach are not randomly distributed throughout the genome.

Copy Number Variants and Exome Sequencing Analysis in Six Pairs of Chinese Monozygotic Twins Discordant for Congenital Heart Disease

This study confirms that chromosomal structure or genetic mutation differences do not seem to play a role in the MZ twins discordant for CHD.

Detecting somatic mosaicism: considerations and clinical implications

Somatic mosaicism is defined with a brief overview of its main mechanisms in concrete clinical examples, the impact of next‐generation sequencing technologies in its detection is discussed, and the clinical implications associated with a discovery in the clinic are expanded.

Somatic Mutations Are Not Observed by Exome Sequencing of Lymphocyte DNA from Monozygotic Twins Discordant for Congenital Hypothyroidism due to Thyroid Dysgenesis

Either somatic mutations are not significant for the etiology of CH or else such mutations lie outside regions of the genome accessible by exome sequencing technology.

The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts

It is shown here that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts, and the spectra and correlation of base substitutions with epigenomic features resemble many cancers.

VarScan2 analysis of de novo variants in monozygotic twins discordant for schizophrenia

The results support the polygenic nature of schizophrenia and the threshold model for its development and show the effectiveness of VarScan2 to identify ‘the needle in the hay stack’ that may cause schizophrenia, specifically in the two patients.

MosaicHunter: accurate detection of postzygotic single-nucleotide mosaicism through next-generation sequencing of unpaired, trio, and paired samples

MosaicHunter is presented, a bioinformatics tool that can identify SNMs in whole-genome and whole-exome sequencing data of unpaired samples without matched controls using Bayesian genotypers and has improved performance compared with other somatic mutation callers.

Somatic mutation load and spectra: A record of DNA damage and repair in healthy human cells

This review focuses on the current methodologies to measure mutation loads and to determine mutation signatures for evaluating the environmental and endogenous sources of DNA damage in human somatic cells.

Whole-Exome Sequencing of Discordant Monozygotic Twin Families for Identification of Candidate Genes for Microtia-Atresia

Objective We used data from twins and their families to probe the genetic factors contributing to microtia-atresia, in particular, early post-twinning variations that potentially account for the



Somatic evolutionary genomics: Mutations during development cause highly variable genetic mosaicism with risk of cancer and neurodegeneration

  • S. Frank
  • Biology
    Proceedings of the National Academy of Sciences
  • 2010
It is suggested that certain types of neurodegeneration, such as amyotrophic lateral sclerosis (ALS), may derive from a small focus of genetically altered cells, and the risk of ALS would be influenced by developmental mutations and the consequent variation in genetic mosaicism.

Somatic APC mosaicism: a frequent cause of familial adenomatous polyposis (FAP)

SNaPshot analysis was proven to be an easy, rapid, and reliable method of confirming low‐level mutations and evaluating the degree of mosaicism and in a fraction of FAP patients the causative APC mutation may not be detected due to weak signals or somatic mosaicism that is restricted to tissues other than blood.

The mutation spectrum revealed by paired genome sequences from a lung cancer patient

A comprehensive view of somatic alterations in a single lung tumour is presented, and the first evidence, to the authors' knowledge, of distinct selective pressures present within the tumour environment is provided.

Somatic mosaicism for chromosome X and Y aneuploidies in monozygotic twins heterozygous for sickle cell disease mutation

The analysis of a pair of generally healthy female MZ twins, discordant for somatic mosaicism for aneuploidy of chromosomes X and Y, illustrates the plasticity of the human genome for tolerating large copy number changes in healthy subjects and shows the sensitivity of the Illumina platform for detection of aberrations that are present in a minority of the studied cells.

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

This study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.

Somatic APC mosaicism: an underestimated cause of polyposis coli

Clinically, the severity of manifestations in offspring and the recurrence risk for siblings of apparently sporadic polyposis patients may be underestimated due to parental APC mosaicism.

Somatic mutations affect key pathways in lung adenocarcinoma

Somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B are found.

Detectable clonal mosaicism from birth to old age and its relationship to cancer

Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) is detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies to identify common deleted regions with genes previously associated with hematological cancers.

Age-related somatic structural changes in the nuclear genome of human blood cells.