The news this week has been dominated by Trump’s plans to cut the NIH budget by 20%. We’re also bracing for the coming storm of announcements/reported results expected from the American College of Medical Genetics conference, which starts in Phoenix, Arizona, tomorrow.

In the nature-nurture debate, twin studies have played a decisive role in helping tease apart the relative contributions of genetics and environment. A meta-analysis of twin studies covers ~18,000 traits and ~15 million pairs of twins, shows an average heritability of 49% across all traits.

Oxford Nanopore have announced the launch of a new desktop product, the GridION X5. It is five of its MinIONs plus a lot of compute in a box, and much smaller than the PromethION. Written up my Omics! Omics!.

Applications

• A “good news” variant in PCSK9 is associated with lower levels of LDL cholesterol and lower chance of heart disease. A large scale clinical trial of a drug that targets PCSK9reported today that it did work, but not as much as analysts had been hoping for, and perhaps not enough to justify the $14,000 price tag.
• More tumors than previously thoughtmay be BRCA1/BRCA2 deficient, meaning that more patients could potentially benefit from PARP inhibitors.
• eGenesis, a spinout of George Church’s lab, has raised $38m in Series A financing. They aim to make pig organs transplantable into humans, using genetic modification to combat organ rejection.
• A clinic in the UK has been the first to be given the go aheadto make three person babies. The UK recently made the procedure legal.
• HudsonAlpha is offering an “elective genome”at $7000. 7 of the first 24 patients had actionable information reported. The focus is on rare disease, one only those genes associated to conditions that the patient has a personal or family history of. The test is in large part being offered because patients ask for it — but this isn’t necessarily good reason to offer a test.
• A number of companies are trying to use DNA as a tracer molecule– an alternative to dyes or radioactive materials.
• Making the case for building the infrastructure to report on protective variants.

New methods

• Apaper showing that an antibiotic compound allows some cells to “read through” premature stop codons, giving hope to those who suffer from rare disease caused by such mutations.
• A group has reported single cell level structural maps of the mammalian genome, at a resolution of less than 100kb. Some things are constant between cells (A and B compartments, lamina-associated domains and active enhancers and promoters), while some vary (individual topological-associated domains and loops).
• Some tumors can be attacked by a combo of drugs that act synergistically. A CRISPR-based double knockout (CDKO) system, designed for high-throughput detection of which pairs of genes give a phenotype when knocked out, allowing synergistic drug target combinations to be identified. Another study of 142k gene-interaction testsreplicated combinatorial drugs at 75% precision.

New genetic associations

• Dan Koboldt has a nice summary of 6 studiesthat pin down genes behind rare disease – an interesting illustration of the diverse set of ways hard-to-solve cases are currently being cracked.
• New genes linked to dilated cardiomyopathy, in a whole exome array based association study of ~3000 cases and ~7000 controls.
• Some variants affecting resistance to anti-depressants.
• Some variants affecting whether your brain will age badlyafter the age of 65
• Another “good news” variant has come to light: a premature stop codon in IL-33 (frequency ~0.65%) has been shown to reduce the risk of asthmain the Icelandic population.
• A study showing that opiate users have excessive histone acetylation, an epigenetic process that regulates gene expression in their brains. The team have already tried a compound designed to limit acetylation in a rat model.