Warning: Since writing this article, it has become clear that the research in question has some serious flaws that came to light after it was published and widely reported. The conclusions here should be treated with caution. UPDATE: The paper has since been retracted.
The developed world is an ageing one. In 2008, the number of pensioners in the UK exceeded the number of minors for the first time in history. Centenarians – those who’ve lived for a century or more – are our fastest-growing demographic. By 2030, ageing baby-boomers will swell the ranks of centenarians to around a million worldwide. That will have important implications, not just socially and economically, but scientifically too. The genomes of these ‘oldest old’ provide a window into the biology of ageing and the secrets to a longer (and healthier) life. It’s a window that Paola Sebastieni from Boston University School of Public Health has just peered through. By studying the genomes of over a thousand centenarians, she has developed a model that can predict a person’s odds of living into their late 90s and beyond with an accuracy of 77%. On the surface, this might seem like a very complicated piece of fortune-telling, but getting accurate predictions isn’t an end unto itself. The point of the exercise is to better understand the full complement of genetic variants that can affect our risk of living to an older age and doing so healthily.
Not Exactly Pocket Science is a set of shorter write-ups on new stories with links to more detailed takes by the world’s best journalists and bloggers. It is meant to complement the usual fare of detailed pieces that are typical for this blog.
Geneticist sequences own genome, finds genetic cause of his disease
If you’ve got an inherited disease and you want to find the genetic faults responsible, it certainly helps if you’re a prominent geneticist. James Lupski (right) from the Baylor College of Medicine suffers from an incurable condition called Charcot-Marie-Tooth (CMT) disease, which affects nerve cells and leads to muscle loss and weakness.
Lupski scoured his entire genome for the foundations of his disease. He found 3.4 million placed where his genome differed from the reference sequence by a single DNA letter (SNPs) and around 9,000 of these could actually affect the structure of a protein. Lupski narrowed down this list of candidates to two SNPs that both affect the SH3TC2 gene, which has been previously linked to CMT. One of the mutations came from his father and the other from his mother. Their unison in a single genome was the cause of not just Lipson’s disease but that of four of his siblings too.
It’s a great example of how powerful new sequencing technologies can pinpoint genetic variations that underlie diseases, which might otherwise have gone unnoticed. The entire project cost $50,000 – not exactly cheap, but far more so than the sequencing efforts of old. The time when such approaches will be affordable and commonplace is coming soon. But in this case, Lupski’s job was easier because SH3TC2 had already been linked to CMT. A second paper tells a more difficult story.
Jared Roach and David Gallas sequenced the genomes of two children who have two inherited disorders – Miller syndrome and primary ciliary dyskinesia – and their two unaffected parents. We don’t know the genetic causes of Miller syndrome and while the four family genomes narrow down the search to four possible culprits, they don’t close the case.
For great takes on these stories and their wider significance, I strongly recommend you to read Daniel Macarthur’s post on Genetic Future, Mark Henderson’s piece in the Times and Nick Wade’s take in the NYT (even if he does flub a well-known concept). Meanwhile, Ivan Oranksy has an interesting insight into the political manoeuvres that go into publicising two papers from separate journals. And check out this previous story I wrote about how genome sequencing was used to reverse the wrong diagnosis of a genetic disorder.
Male moths freeze females by mimicking bats
Flying through the night sky, a moth hears the sound of danger – the ultrasonic squeak of a hunting bat. She freezes to make herself harder to spot, as she always does when she hears these telltale calls. But the source of the squeak is not a bat at all – it’s a male moth. He is a trickster. By mimicking the sound of a bat, he fooled the female into keeping still, making her easier to mate with.
The evolutionary arms race between bats and moths has raged for millennia. Many moths have evolved to listen out for the sounds of hunting bats and some jam those calls with their own ultrasonic clicks, produced by organs called tymbals. In the armyworm moth, only the males have these organs and they never click when bats are near. Their tymbals are used for deceptive seductions, rather than defence.
Ryo Nakano found that the male’s clicks are identical to those of bats. When the males sung to females, Nakano found that virtually all of them mated successfully. If he muffled them by removing the tymbals, they only got lucky 50% of the time. And if he helped out the muted males by playing either tymbal sounds or bat calls through speakers, their success shot back up to 100%. Nakano says that this is a great example of an animal evolving a signal to exploit the sensory biases of a receiver.
More on bats vs. moths from me
Reference: Biology Letters http://dx.doi.org/10.1098/rsbl.2010.0058
Meet !Gubi, the tribal elder of a group of Bushmen (or Khoisan), one of the oldest known human lineages. He lives the life of a hunter-gatherer in the Namibian part of the Kalahari Desert. But he also has a strange connection to James Watson, the
British American scientist who helped to discover the structure of DNA. For a start, they’re both around 80 years old. But more importantly, they are two of just 11 humans to have their entire genomes sequenced.
Along with Archbishop Desmond Tutu, !Gubi is one of two southern Africans, whose full genomes have been sequenced by Stephan Schuster and an international team of scientists . Schuster’s team also analysed the genes of three other Bushmen – G/aq’o, D#kgao and !Aıˆ (see footnote for pronunciation guide) – focusing on the parts of their genome that codes for proteins. Like, !Gubi, these men are tribal elders and all are around 80 years old. Despite the fact that the four Bushmen come from neighbouring parts of the Kalahari, their genetic diversity is astounding. Pick any two and peer into their genomes and you’d see more variety than you would between a European and an Asian.
This diversity reveals just how important it is to include African people in genome sequencing projects. Until now, the nine complete human genomes have included just one African – a Yoruban man from Nigeria. The rest have hailed from Europe, America, China, Korea and, most recently, Greenland circa 4,000 years ago. This is a major oversight. Africa is the birthplace of humanity and its people are the most genetically diverse on the planet. To understand human genetics without understanding Africa is like trying to learn a language by only looking at words starting with z.
The Bushmen certainly provide a glimpse into this diversity. Desmond Tutu was also selected because his ancestry covers the two largest of southern Africa’s Bantu groups – the Tswama and the Nguni – making him an excellent representative for many southern Africans. Vanessa Hayes, who worked on the study, says, “This work is very expensive so we wanted to maximise the amount of diversity we could get in one individual.” The team had other reasons for sequencing the bishop.”He’s a voice for southern Africans and for his people. He’s a chairman of the Global Elders. He provides a genome with a lot of medical history behind it, having survived prostate cancer, polio and Tb, diseases that affect many southern Africans.” But most importantly, Hayes says, “He wanted to participate. He himself wanted to study medicine so this for him was a personal endeavour.”
The researchers hope that their new data will allow medical research to become more inclusive. Vanessa Hayes, who led the study, says that she found HIV research in South Africa to be very difficult because most genetic databases are severely Eurocentric, which rules out a lot of Africans from medical research. Without this knowledge, for example, we have no way of knowing if a drug that was developed and tested in Western patients will have the same benefits and risks in African ones.