Genomic and Ancestry
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Researchers develop powerful single-cell epigenetic methylation mapping to study environmental effects on DNA

Researchers develop powerful single-cell epigenetic methylation mapping to study environmental effects on DNA | Genomic and Ancestry | Scoop.it

Researchers at the BBSRC-funded Babraham Institute, in collaboration with the Wellcome Trust Sanger Institute Single Cell Genomics Centre, have developed a powerful new single-cell technique to help investigate how the environment affects our development and the traits we inherit from our parents. The technique can be used to map all of the ‘epigenetic marks’ on the DNA within a single cell.  This single-cell approach will boost understanding of embryonic development, could enhance clinical applications like cancer therapy and fertility treatments, and has the potential to reduce the number of mice currently needed for this research.

 

‘Epigenetic marks’ are chemical tags or proteins that mark DNA and act as a kind of cellular memory. They do not change the DNA sequence but record a cell’s experiences onto the DNA, which allows cells to remember an experience long after it has faded. Placing these tags is part of normal development; they tell genes whether to be switched on or off and so can determine how the cell develops. Different sets of active genes make a skin cell different from a brain cell, for example. However, environmental cues such as diet can also alter where epigenetic tags are laid down on DNA and influence an organism’s long-term health.

 

Dr Gavin Kelsey, from the Babraham Institute, said: “The ability to capture the full map of these epigenetic marks from individual cells will be critical for a full understanding of early embryonic development, cancer progression and aid the development of stem cell therapies.

 

“Epigenetics research has mostly been reliant on using the mouse as a model organism to study early development. Our new single-cell method gives us an unprecedented ability to study epigenetic processes in human early embryonic development, which has been restricted by the very limited amount of tissue available for analysis.”

 

The new research, published in Nature Methods, offers a new single-cell technique capable of analysing DNA methylation – one of the key epigenetic marks – across the whole genome. The method treats the cellular DNA with a chemical called bisulphite. Treated DNA is then amplified and read on high-throughput sequencing machines to show up the location of methylation marks and the genes being affected.

 

These analyses will help to define how epigenetic changes in individual cells during early development drive cell fate. Current methods observe epigenetic marks in multiple, pooled cells. This can obscure modifications taking place in individual cells at a time in development when each cell has the potential to form in a unique way. The new method has already revealed that many of the methylation marks that differ between individual cells are precisely located in sites that control gene activity.


Via Dr. Stefan Gruenwald
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Frontiers | A simulation study of gene-by-environment interactions in GWAS implies ample hidden effects | Evolutionary and Population Genetics

The switch to a modern lifestyle in recent decades has coincided with a rapid increase in prevalence of obesity and other diseases. These shifts in prevalence could be explained by the release of g...
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Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer | Genomic and Ancestry | Scoop.it

Evidence from twin and family studies suggests an inherited genetic component to epithelial ovarian cancer (EOC) risk. Rare, high-penetrance alleles of genes such as BRCA1 and BRCA2 account for about 40% of excess familial risk, and GWAS have recently identified common risk alleles at 9p22, 8q24, 2q31 and 19p13, with two additional loci at 3q25 and 17q21 that approached genome-wide significance. However these alleles only explain 4% of excess familial risk, and more risk loci probably exist.

 

A study group therefore recently pooled the data from two GWAS to inform the selection of SNPs for a large-scale replication. The North American study comprised 4 independent case-control studies that included 1,952 cases and 2,052 controls. The second study was a 2-phase multicenter GWAS that included 1,817 cases and 2,354 controls in the first phase and 4,162 cases and 4,810 controls in the second phase.

 

The researchers carried out a fixed-effects meta-analysis from the two GWAS for ~2.5 million genotyped or imputed SNPs. They selected 24,551 SNPs associated with the risk of either all-histology (11,647 SNPs) or serous (12,904 SNPs) ovarian cancer on the basis of ranked P values. They designed assays for 23,239 SNPs and included them on a custom Illumina Infinium iSelect array (iCOGS) comprising 211,155 SNPs designed by the Collaborative Oncological Gene-environment Study (COGS) to evaluate genetic variants for association with risk of breast, ovarian and prostate cancers. They then genotyped these SNPs in cases and controls from 43 individual studies from the Ovarian Cancer Association Consortium (OCAC) that were grouped into 34 case-control strata. These included most of the samples genotyped in the initial GWAS. An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.  


Via Dr. Stefan Gruenwald
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Dmitry Alexeev's curator insight, June 27, 2013 1:23 AM

is that a new method, Vova)?

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Back to Basics: Using GWAS to Drive Discovery for Complex Diseases

Genome-wide association studies (GWAS) have been providing valuable insight to the genetics of common and complex diseases for nearly 10 years. Despite some ...
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GWAS study shows that human intelligence is highly heritable and polygenic

GWAS study shows that human intelligence is highly heritable and polygenic | Genomic and Ancestry | Scoop.it

Individual differences in intelligence are strongly associated with many important life outcomes, including educational and occupational attainments, income, health and lifespan. Data from twin and family studies are consistent with a high heritability of intelligence, but this inference has been controversial. We conducted a genome-wide analysis of 3511 unrelated adults with data on 549 692 single nucleotide polymorphisms (SNPs) and detailed phenotypes on cognitive traits. http://tinyurl.com/6p9lp3h


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Genetic Recombination and Gene Mapping

In this video Paul Andersen explains how the frequency of recombination between linked genes can be used to determine the relative location of genes on a chr...
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