Genome sequencing for sale on the NHS

NHS to sell DNA tests to healthy people in push to find new treatments

Service will be free for patients with serious genetic conditions as health service in England aims to recruit 5 million volunteers

“Major advances have been made in the field of genomics in recent years. We are now able to sequence the entire genome. Rapid advances in genetic technologies have led to greater availability, and at lower costs, of all forms of genetic tests, ranging from online direct to consumer DNA test kits to clinical whole genome sequencing of all 20 000 human genes.

England’s health secretary, Matt Hancock, recently announced plans to offer healthy people the option to have their whole genome sequenced by the NHS for an as yet undisclosed fee (thought to be a few hundred pounds). These “genomics volunteers” would receive a personalised health report indicating genetic risks of various diseases including cancer, dementia, and cardiovascular disease. These extensive personal genomic data will be shared with researchers to provide opportunities to improve our understanding of human diseases.

This proposal raises several important clinical, logistic, social, and ethical issues, …”

Continue reading Think again, Mr Hancock, on The BMJ, 25 February 2019.

Genomic imprinting disorders

Lessons on how genome, epigenome and environment interact

2019 Study Abstract

Genomic imprinting, the monoallelic and parent-of-origin-dependent expression of a subset of genes, is required for normal development, and its disruption leads to human disease.

Imprinting defects can involve isolated or multilocus epigenetic changes that may have no evident genetic cause, or imprinting disruption can be traced back to alterations of cis-acting elements or trans-acting factors that control the establishment, maintenance and erasure of germline epigenetic imprints.

Recent insights into the dynamics of the epigenome, including the effect of environmental factors, suggest that the developmental outcomes and heritability of imprinting disorders are influenced by interactions between the genome, the epigenome and the environment in germ cells and early embryos.

This review focuses on imprints that effect essentially permanent and ubiquitous changes on gene expression potential at affected loci, as opposed to tissue-specific or transient changes.

DES and the GENES

High genetic correlations found between six psychiatric disorders

Personality Traits and Psychiatric Disorders Linked to Specific Genomic Locations

A meta-analysis of genome-wide association studies (GWAS) has identified six loci or regions of the human genome that are significantly linked to personality traits, report researchers at University of California San Diego School of Medicine in this week’s advance online publication of Nature Genetics. The findings also show correlations with six psychiatric disorders.


Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown.

We identified six genetic loci, including five novel loci2, 3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genome-wide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759).

Some genetic variants linked to extraversion and neuroticism personality traits have been identified.

The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit–hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety).

In addition, there were high genetic correlations between extraversion and attention deficit hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. Neuroticism was genetically correlated with internalized psychopathologies, such as depression and anxiety.

Study and Press Release

Should doctors ever be allowed to modify the human species?

Genome editing: ethical considerations

Nuffield Council on Bioethics report – Genome editing: an ethical review – found materials to perform basic experiments are now available to ‘garage scientists.

“… genetic technology has become so powerful that nations need to decide whether or not doctors should ever be allowed to modify the human species.

While the creation of GM humans is not on the horizon yet, the risks and benefits of modifying a person’s genome – and having those changes pass on to future generations – are so complex that they demand urgent ethical scrutiny, …

Read Experts warn home ‘gene editing’ kits pose risk to society, the guardian, 30 September 2016. Download the ethical review short guide.

Identification of candidate anti-cancer molecular mechanisms of compound kushen injection using functional genomics

Study shows how Chinese medicine kills cancer cells

Australian researchers at the University of Adelaide, Department of Genetics and Evolution, School of Biological Sciences, have shown how a complex mix of plant compounds derived from ancient clinical practice in China – a traditional Chinese medicine – works to kill cancer cells.


Compound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours. However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion.

Identification of candidate anti-cancer molecular mechanisms of compound kushen injection using functional genomics, Impact Journals, September 1, 2016.

Red leaves by by wallygrom.

We have used the MCF-7 human breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression. Cells were treated with CKI for 24 and 48 hours at two concentrations (1 and 2 mg/mL total alkaloids), and the effect of CKI on cell proliferation and apoptosis were measured using XTT and Annexin V/Propidium Iodide staining assays respectively. Transcriptome data of cells treated with CKI or 5-Fluorouracil (5-FU) for 24 and 48 hours were subsequently acquired using high-throughput Illumina RNA-seq technology. In this report we show that CKI inhibited MCF-7 cell proliferation and induced apoptosis in a dose-dependent fashion.

We integrated and applied a series of transcriptome analysis methods, including gene differential expression analysis, pathway over-representation analysis, de novo identification of long non-coding RNAs (lncRNA) as well as co-expression network reconstruction, to identify candidate anti-cancer molecular mechanisms of CKI. Multiple pathways were perturbed and the cell cycle was identified as the potential primary target pathway of CKI in MCF-7 cells. CKI may also induce apoptosis in MCF-7 cells via a p53 independent mechanism. In addition, we identified novel lncRNAs and showed that many of them might be expressed as a response to CKI treatment.

HGP-Write: Testing Large Synthetic Genomes in Cells

Scientists want to synthesize the human genome. What does that mean?

Scientists Talk Privately About Creating a Synthetic Human Genome, nytimes, MAY 13, 2016.

Scientists met at Harvard University recently to discuss the fabrication of a human genome, meaning they would use chemicals to manufacture all the DNA contained in human chromosomes.

The project, called HGP-Write, is spurring both intrigue and concern in the scientific communities because it may become possible, such as through cloning, to use a synthetic genome to create human beings without biological parents.

Scientists Want To Synthesize The Human Genome. What Does That Mean?, newsy, May 15, 2016.

Image James King-Holmes/Science Source.

The Human Genome Project was aimed at reading the sequence of the three billion chemical letters in the DNA blueprint of human life. The new HGP-Write project would involve writing the human genome – synthesizing all the three billion units data from chemicals – and could have a big “scientific payoff“…

Genes associated with Breast Cancer and mutational signatures that influence tumour development

Personalized Breast Cancer Treatment Gets Closer to Reality

Five new breast cancer genes and range of mutations pave way for personalized treatment, eurekalert, 2 MAY-2016.

The largest-ever study to sequence the whole genomes of breast cancers has uncovered five new genes associated with the disease and 13 new mutational signatures that influence tumour development. The results of two papers published in Nature and Nature Communications also reveal what genetic variations exist in breast cancers and where they occur in the genome.


Landscape of somatic mutations in 560 breast cancer whole-genome sequences, nature, 02 May 2016.

We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

Genome Sequencing Study of Autism

Frequency and Complexity of De Novo Structural Mutation in Autism


Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches.

By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes.

Frequency and Complexity of De Novo Structural Mutation in Autism, The American Journal of Human Genetics,, March 24, 2016.

We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement.

Investigating Causes of Epigenomic and Genomic Errors

Germline Exposures March3, 2016 Webinar


Upcoming webinar, March 3, 2016, 1-3pm EST: “Environmental Exposures and the Germline: Investigating Causes of Epigenomic and Genomic ErrorsRegister here.

As evidence mounts that some forms of autism are driven by “de novo” errors in the germline (genomic glitches not present in either parent), the question arises: what environmental factors might contribute to this phenomenon? Leading researchers will delve into questions of germline plasticity, genotoxic exposures, and molecular events that affect DNA.


  • Dana Dolinoy, PhD, University of Michigan
    “Heritable epigenetic effects of germline exposure to toxicants”
    • Watch webinar with Dr. Dolinoy on Epigenie
  • Carole Yauk, PhD, Health Canada
    “Analysis of chemical exposures and life stage factors that contribute to genetic disease”. Read Yauk et al: “Approaches for Indentifying Germ Cell Mutagens
  • With commentary by: Cathrine Hoyo, PhD, UNC, and Lisa Chadwick, PhD, NIEHS

This 2-hour webinar, open to researchers and the public, is free, but you must pre-register. Spaces are limited. Register here.

Sources Germline Exposures.

U.K. researcher receives approval to genetically modify human embryos

HFEA approval for new “gene editing” techniques

Scientists in Britain have been give the go-ahead to edit the genes of human embryos for research purposes, using a technique that some say could eventually be used to create “designer babies”.

The Human Fertilisation and Embryology Authority (HFEA) has approved a research application from the Francis Crick Institute to use new “gene editing” techniques on human embryos (see Licence Committee – minutes).

The aim of the research, led by Dr Kathy Niakan, a group leader at the Crick, is to understand the genes human embryos need to develop successfully.

The work carried out at the Crick will be for research purposes and will look at the first seven days of a fertilised egg’s development (from a single cell to around 250 cells).

The knowledge acquired from the research will be important for understanding how a healthy human embryo develops.

This knowledge may improve embryo development after in vitro fertilisation (IVF) and might provide better clinical treatments for infertility, using conventional medical methods.

Paul Nurse, director of the Crick, said:

“I am delighted that the HFEA has approved Dr Niakan’s application. Dr Niakan’s proposed research is important for understanding how a healthy human embryo develops and will enhance our understanding of IVF success rates, by looking at the very earliest stage of human development – one to seven days.”

In line with HFEA regulations, any donated embryos will be used for research purposes only and cannot be used in treatment. These embryos will be donated by patients who have given their informed consent to the donation of embryos which are surplus to their IVF treatment.

The genome editing research now needs to gain ethical approval and, subject to that approval, the research programme will begin within the next few months.

Press releases

  • Britain gives scientist go-ahead to genetically modify human embryos, reuters, Feb 1, 2016.
  • CRISPR Editing of Human Embryos Approved in the U.K., genengnews, Feb 1, 2016.
  • In a world first, UK scientists just got approval to edit human embryos, vox, February 1, 2016.
  • U.K. Approves First Studies of New Gene Editing Technique CRISPR on Human Embryos, time, Feb 1, 2016.
  • UK researcher gets go-ahead to create embryos using CRISPR, siliconrepublic, Feb 1, 2016.