Well, an embarrassing amount of time has passed since I posted last. I am on the road in South America, but was feeling increasingly angsty about being behind on genomics happenings. So I have spent the last three days catching up. Here is my pick of the most interesting developments:
Close to society
- The Golden State Killer left DNA behind at many of his crime scenes from 1974-86. The DNA did not lead to any suspect until April of this year, when an officer uploaded the killer’s genetic profile to an open source genetic database designed to help people find relatives. They got a partial hit to a family member, and used this to identify a suspect subsequently found to be a match to the killer. The same technique has been used for other cases. I will write much more extensively about this case separately.
- A good investigational piece, using data from a new database, that shows that pharma contributions to patient advocacy groups dwarf their spend on lobbying.
- The All of Us program has officially launched (formerly the Precision Medicine Initiative). The project aims to enroll 1 million US residents, and anyone over the age of 18 can sign up. The first interview question Scientific American asked the program’s director Eric Dishman was about the golden state killer case, the response was that law forbids one federal agency sharing data from the program with another, even if subpoenaed. A moving story from WIRED about some of the individuals behind the diversity programs for the project.
- Dubai Health Authority (DHA) is planning to map the genomes of all of its residents. It aims to “issue reports that support research, forecast future disorders and epidemics, and plan preventive measures.”
- In the wake of the separation of families by US border control, 23andMe offered its tests to hep reunite the families. Many were swift to point out that genetics in the hands of US border control is a scary prospect.
- The biohacker scene has been in the spotlight thanks in particular to the combination of some headline grabbing antics (e.g. live self injection with gene therapies) and prominent voices raising concern (see e.g. here). The recent death of one of the leading activists, Aaron Traywick, has given the nascent field pause for reflection.
- African scientists have formalized a voluntary framework aimed to prevent foreign researchers from using African genetic data without involving African scientists (“helicopter science”).
- In a startling combination of buzz words, there is a plan to publish the cannabis genome to a blockchain, as a challenge to the conventional scientific publishing market. The idea is that this model will give a permanent, transparent record of a scientific advance, preventing corporations from laying claim to certain advances.
- The EarthBioGenome project (EBP), which aims to sequence the ~1.5 million known eukaryotic species in the next 10 years, is facing up to some of its challenges, including finding funding for the endeavor, which has an estimated price tag of ~$5b.
Close(r) to the clinic
- Liquid biopsy — a major early player is withdrawing, and ASCO/CAP have said that they don’t see a role for the tests outside of clinical trials.
- Geisinger’s whole exome efforts are moving beyond research. Long at the forefront og genomic medicine, they are piloting a clinical whole exome, with a view to sequence every one of its patients at birth.
- It has long been argued whether knowing information about genetic risk actually improves health outcomes by altering behavior. A new study using risk score for cardiac health risks did find changes in behavior.
- Taking the precision medicine approach to arthritis
- A prospective study of a polygenic risk score, this one for Atrial Fibrillation, showed reasonable prognostic abilities.
- Proof of concept for nanopore sequencing for Pre-implatation Genetic Screening – quicker, and potentially cheaper.
- Researchers have shows that they can use circulating placental DNA in the mother’s blood to predict the due date of the baby as reliably (and hopefully cheaper) as first trimester ultrasounds, and can also discriminate those at risk of a pre-term birth.
- Color genomics in spearheading the route of self-insured employers, who offer tests as benefits, to bring genomics to a wider audience, as a way to make a case for population based breast cancer risk screening.
New science
- The interstitium, a fascinating story of how a quirk of technology lead to us overlooking what is now classified as our largest organ.
- More on the somatic genome: we all have pieces of circular DNA, formed from breakpoints.
- In a new chapter for how nurture can shape nature, the not so static genome: How attentive a mother is to her babes correlates with how many copies of the jumping gene L1 the babies have.
- In another contribution to the nature-nurture debate, genetic risk for schizophrenia is modulated by the placental environment – schizophrenia patients who had these early life complications (ELCs) had higher polygenic risk scores, and the genetic scores better predicted schizophrenia presence in individuals with ELCs. The genes involved are expressed in the placenta during complicated pregnancies, signalling a placenta under stress.
- A large study (265,218 patients and 784,643 controls) found that whereas the underlying genetic risk for each neurological disorder tends to be distinct, there is a lot of overlap for psychiatric conditions, adding evidence that “current clinical boundaries do not reflect distinct underlying pathogenic processes” for psychiatric conditions.
- Transposons make up half the mammalian genome, and have long been thought to be functionally inert. A study shows that one transposon is necessary for normal embryo development.
- A role for pericentromic Satellite DNA, part of the non-coding DNA previously without a known function, has been shown to be vital in holding the genome together in the nucleus, through a protein called D1 that binds to it and helps hold chromosomes together.
- A good news genetic variant protects against liver disease.
- And more work that highlights the role of rare variants, from a study that uses a large cohort of de-identified EHR data and genetic data to identify patients who have symptoms associated with rare genetic diseases, to try and identify those who may have an identified genetic condition, and then looking for common underlying genetics of those identified.
- Advances in DNA computing.
Genetic modification
- The FDA put the brakes on the first US based CRISPR clinical trial, for unspecified reasons.
- “Genome surgery is coming”, says the team that reports the first successful results of find-and-replace CRISPRing of a heterozygous mutation causing in a retinal disease. The challenge in these autosomal conditions is to just target the faulty version.
- CRISPRing cells can activate the cell’s DNA repair mechanism pathways, specifically that involving p53. This can cause a selective advantage for cells that have a compromised p53 pathway, i.e. CRISPR can lead to a selective advantage for cancerous cells. The conclusion “p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9”.
- The US Department of agriculture announced that it will not regulate genetically edited plants, on the basis that they could have been produced by classical breeding techniques.
- The Association for Responsible Research and Innovation in Genome Editing (ARRIGE) has been formed
- The scientists that published the widely cited study that CRISPRing cells led to many off target effects have been unable to replicate their results.
- Epigenetic version of CRISPR shown to work in vitro.
Spotlight on genetics and intelligence
Pedigree-based analysis, in particular twin based studies, give us estimates that variance in intelligence is about 50-80% inherited. Previous work in genetics had not identified much of this variance (for intelligence and all other complex traits), leading to a “heritability gap”. A study of over 20,000 individuals, many from the same families, who had been SNP genotyped at 700,000 locations claims it can explain about 54% of the variance in general intelligence with genetics, substantially closing the heritability gap. They were able to close the gap through assessing the contribution of rarer variants, finding that variants with a frequency less than 1% contribute 23% of the variance. It looks like prior genotype based work missed causal variants in low linkage disequilibrium with genotyped SNPs — variants they were able to find because of the related individuals in their dataset.
One might wonder, why bother studying the genetics of intelligence? The justification given by these papers is through the fact that intelligence correlates with health outcomes, and so a better understanding could lead to better health outcomes.
Another study presents data showing that “genetic and exam differences between school types are primarily due to the heritable characteristics involved in pupil admission”
Spotlight on genetics and race
And finally, an op-ed by Harvard geneticist David Reich titled “How Genetics Is Changing Our Understanding of ‘Race’” has stirred up an old can of worms, by claiming that political correctness is stifling science by refusing to acknowledge genetic differences between the “races”. The likes of Sam Harris have jumped on the bandwagon. The sentence “But as a geneticist I also know that it is simply no longer possible to ignore average genetic differences among ‘races.’” is the most controversial (in the book that the op-ed is mostly taken from, the same sentence uses the term “populations”). Here is an extract from an open letter that drives home the difference between races and populations: “In short, there is a difference between finding genetic differences between individuals and constructing genetic differences across groups by making conscious choices about which types of group matter for your purposes. These sorts of groups do not exist “in nature.” They are made by human choice. This is not to say that such groups have no biological attributes in common. Rather, it is to say that the meaning and significance of the groups is produced through social interventions.” Its clear how socially constructed of a term “race” has been, particularly in the US, where e.g. a single black ancestor would make you “black” under the one-drop rule. Many of Reich’s points would stand if he stuck to the terms “ancestry” or “population”. Possibly even the point that the proximity between ancestral populations and race makes some scientists timid in their explorations and communications.
(The whole debate reminds me that race, when gathered in scientific studies, is always self-reported, and hence any links to biology are very suspect. This point has been made by bioethicists in connection with the FDA’s approval of the drug BiDil just for those who identify as black.)
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