Round-up Feb 9th – Feb 18th

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News from the AGBT Conference, Feb 10th – Feb 13th

 

Research and Reviews

Market News

 

Round-up, Feb 2nd – Feb 8th

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23andMe links being a morning person and genetics. The GWAS type analysis found 15 regions, several near known circadian rhythm genes. http://www.nature.com/ncomms/2016/160202/ncomms10448/full/ncomms10448.html

Oxford Nanopore’s MinION has been at work, producing “real time, portable sequencing for Ebola surveillance”: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature16996.html Using the MinION (which weighs less than 100g), “We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15–60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.”

Last February, the UK approved the creation of three person embryos, where the mitochondria came from a third donor. The FDA had requested an Institute of Medicine report on the technique. Published this week, the report concluded with various caveats that it could be ethical — but limited to male embryos for the moment (males do not pass on mitochondria, so the changes made would affect only the individual in question). http://www.nap.edu/catalog/21871/mitochondrial-replacement-techniques-ethical-social-and-policy-considerations. However, the latest federal budget “prevents the FDA from using funds to review applications in which a human embryo is intentionally created or modified to include” changes that could be passed down to future generations.

A link between genes near an individual’s disrupted transcription factor binding sites and their phenotype data is established in this paper, in a further foray beyond the exome: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004711. This mutational load/burden style approach used data from five individuals who have made both their whole genomes and medical histories public.

Common disease: the product of many common variants, or a few rare ones? GWAS, which only look at common variants, have not been able to explain much genetic predisposition. This study looked at both common and rare variants for AMD http://www.ncbi.nlm.nih.gov/pubmed/26691988: “Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.” Also see a writeup at MassGenomics http://massgenomics.org/2016/02/rare-variant-studies-of-common-disease.html.

Two reasons senescent cells (those that no longer undergo cell division) have been in the news.

 

In a follow on to the case of the child who was forced to leave a Palo Alto school because he was a CF carrier, the U.S. Departments of Education and Justice have filed a brief siding with the family and against Palo Alto school district, arguing that the decision violoated both his first ammendament prviacy rights and the Americans with Disabilities Act http://www.paloaltoonline.com/news/2016/02/08/feds-weigh-in-on-palo-alto-dna-privacy-case

A Nature Editorial draws attention to how hard it is to get a paper corrected or retracted, even if it is clearly wrong, and even by the authors of the study: http://www.nature.com/news/reproducibility-a-tragedy-of-errors-1.19264

 

Round-up, Jan 27th – Feb 1st

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In the biggest genetics discovery of the week, the first link between molecular processes and the onset of schizophrenia has been reported. Previously, case-control studies had pointed to the major histocompatibility complex on chromosome 6. This study pins down structurally diverse alleles of the complement component 4 genes, which are involved in tagging synapses for pruning during brain development. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature16549.html, and a NYT write-up http://www.nytimes.com/2016/01/28/health/schizophrenia-cause-synaptic-pruning-brain-psychiatry.html
A write up of a fascinating case of a boy who was removed from a Palo Alto school because he had a cystic fibrosis genetic marker: http://www.buzzfeed.com/stephaniemlee/this-boy-was-thrown-out-of-school-because-of-his-dna-parents
And while on legal matters, GINA is the legislation that protects what can be done with your genetic material, and there’s a proposal to somewhat loosen it, to better enable Affordable Care Act type wellness plans: http://www.eeoc.gov/laws/regulations/qanda-gina-wellness.cfm. The Genetic Alliance is opposing, here’s a blog post that outlines their opposition: http://www.genomicslawreport.com/index.php/2016/01/25/eeoc-tries-to-harmonize-acas-promotion-of-employer-wellness-programs-with-ginas-ban-against-employer-access-to-genetic-information-of-employees-and-employees-family-members/
A British scientist has been given the go ahead to modify human embryos using CRISPR-Cas9, in an effort to ultimately help improve IVF success rates: http://news.yahoo.com/britain-gives-scientist-ahead-genetically-modify-human-embryos-111100612.html. Queue talk of designer babies.
And on research ethics, just in case you hadn’t spotted it, this NEJM editorial about “research parasites” has been causing a twitter storm: http://www.nejm.org/doi/full/10.1056/NEJMe1516564. Research parasites are those “people who had nothing to do with the design and execution of the study but use another group’s data for their own ends, possibly stealing from the research productivity planned by the data gatherers, or even use the data to try to disprove what the original investigators had posited.”
A report of the first patient identified with three independent autosomal-recessive single-gene disorders.  “We propose that blended phenotypes resulting from several concomitant single-gene disorders in the same patient likely account for a proportion of presumed monogenic disorders of currently unknown cause and contribute to variable genotype-phenotype correlations.” http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg2015285a.html
An interesting company that takes the output of a cancer screening test as input to not only help find clinical trials, but others with the same mutation profile, and easily digestible “stories” about particular mutations: http://www.cureforward.com/#/viewstory
A study making the case for the cost effectiveness of population wide carrier screening based on NGS over SNP genotyping, or no testing at all (no prices for guessing line of business of study writers): http://onlinelibrary.wiley.com/doi/10.1002/mgg3.204/abstract
A Geisinger based team have done a literature aggregation exercise to produce a database of genes involved in neurodevelopmental disorders: http://geisingeradmi.org/care-innovation/studies/dbd-genes/

Round-up, Jan 10th – 26th

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(I know this covers more than one week… not off to a good start!)

Jan 11th-14th was the JPMorgan conference, with several announcements coming from the annual gathering of biotech top brass. 

Ilumina announced Grail, a product that will attempt to detect early stage cancer from blood. Isn’t this stepping on their customers’ toes? Their CEO Flatley on this point: “In this case, we didn’t think the market could do it fast enough, unless we destroyed our [business] by giving away sequencing. We don’t think anyone else can do it at scale. And there are millions of lives at stake.” The project will involve Clinical trails of >30,000 people; $100m investment; test available 2019. http://www.technologyreview.com/news/545326/illuminas-bid-to-beat-cancer-with-dna-tests/

Just a few days later, Obama announced his “cancer moonshot” (and was careful to avoid the word ‘cure’): Biden is in charge of “mission control”.  http://www.scientificamerican.com/article/can-we-truly-cure-cancer/

I thought this was interesting to hear from Myriad (from JPMorgan): “Capone also reiterated that 80 percent of samples the firm receives for hereditary cancer testing are now orders for its myRisk Hereditary Cancer panel, a 25-gene, next-gen sequencing-based test. And despite competitors entering the market, he said the firm hasn’t seen a lot of price erosion, which he attributed to Myriad’s lab accuracy, variant classification database, and customer support”. https://www.genomeweb.com/business-news/jp-morgan-healthcare-conference-day-one-23andme-myriad-genetics-genomic-health-alere

And while still on the subject of cancer, NCI-Match is a basket trail for precision medicine cancer therapies: you send in your sample, it assigns you to a trial based on the variants. Its been very popular, but had spectacularly low matching rates to date. Genomeweb’s piece is an interesting read: https://www.genomeweb.com/molecular-diagnostics/nci-match-sees-lots-enthusiasm-initial-months-not-many-matches. Comparison point to current start of the art: “At Mass General, where doctors routinely perform next-generation sequencing on metastatic cancer patients and have access to an extensive portfolio of studies that they could potentially place patients in, more than 40 percent of patients receive actionable results.” 

DNASimple, a Y combinator startup, is growing a database of DNA donors (rare disease, other), who they will ask for saliva samples if a research project needs them. https://www.genomeweb.com/sequencing-technology/startup-dnasimple-aims-provide-genetic-researchers-donor-samples

We’ve seen quite a lot of high-throughput experimental approaches to determine effect of unseen variants (e.g. this early study on missense variants in BRCA1: http://cancerdiscovery.aacrjournals.org/content/3/10/1142.short). Here’s a company that is doing similar things to build up a database aimed at “eliminating variants of unknown significance”: https://ranomics.com/

And my picks of interesting science:

CRSIPR-Cas9 was used in child and adult mice models of Muscular Dystrophy to restore dystrophin function, the protein that is needed for normal muscular function, with promising results — bringing gene editing cures much closer: http://www.nature.com/nature/journal/v529/n7585/full/529130b.html

A review of non-coding variants in cancer. Table 1 gives a nice summary of non-coding annotation source — ENCODE the clear leader, but plenty of others: http://www.nature.com/nrg/journal/vaop/ncurrent/full/nrg.2015.17.html

In good news for interpreting non-coding regions, high-throughput use of CRISPR-Cas9 to investigate effect of variation on regulatory regions. http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3468.html

More links reported between CNVs and autism http://www.nature.com/articles/srep19372

New sequencing technologies to keep an eye on: scientists at NIST are developing a graphene based “hybrid solid-state and biological nanopore”. http://www.nist.gov/mml/acmd/nist-simulates-fast-accurate-dna-sequencing-through-graphene-nanopore.cfm

A randomized, controlled trial to see if it is a good idea to disclose secondary findings to patients concludes “yes”: http://annals.org/article.aspx?articleid=2484285

Here’s a study that investigates over 4000 genes are only expressed on one chromosome (relevant for interpreting a heterozygous loss of function variant), which reports that these genes are subject to a lot of intra-human variation — you often see high frequency variants in these genes. http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3493.html.

Finally, do we have ten times as many bacterial cells as human cells in our bodies? No, the ratio is more like 1:1. http://biorxiv.org/content/early/2016/01/06/036103

Genomics: what’s in a name?

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Genome, derived from Gene, traces its roots via Pangen to Darwin’s controversial notion of Pangenesis.

Darwin’s decades of research on the inheritance of characteristics had left open an important question. What was the mechanism of inheritance? In 1868, nearly ten years after the publication of The Origin of Species, he framed a hypothesis, which he termed Pangenesis, from the Greek pan (a prefix meaning “whole”, “encompassing”) and genesis (“birth”). He hypothesized the existence of particles, named gemmules, which were shed by every part of the body before coming together in the sperm or egg. It allowed for the possibility of the inheritance of acquired characteristics, and was never that popular.

In 1889 a Dutch botanist called Hugo de Vries proposed his own theory of the inheritance of characteristics, also based on hypothesized particles. He called these pangenes, later shortened to genes.

But what was a gene? Biochemists had been studying the molecules on which life is based, including the cellular components termed chromosomes. In 1910, an American scientist, Thomas Hunt Morgan, was pioneering a new field of study at the intersection of genetics and biochemistry, now known as molecular biology. He was able to show, via a series of experiments on fruit flies, that genes resided on chromosomes. Genes had suddenly become physical. The term genome, introduced in 1920, is a fusion of gene and chromosome, and means the totality of an organism’s genetic material.

In 1987, a group of molecular biologists that were studying the structure, function and evolution of genomes, proposed the term genomics as the title of a new journal. The “-omics” suffix has come to imply the systematic, large-scale, data-driven study of a given domain.

It seems very fitting to have a name that incorporates three essential aspects of the field: inherited information, its physical manifestation, and methodology.