Decoding the genes of cognition
Interview: Dr Silvia Paracchini (University of St Andrews)…
Decoding the genes of cognition
Dr Silvia Paracchini has been a Royal Society University Research Fellow at the University of St Andrews since 2011. Her research group at the School of Medicine investigates the genetic components of behavioural traits such as handedness and common neurodevelopmental disorders such as dyslexia, to understand the mechanisms underlying human cognition. She graduated in Biological Sciences from the University of Pavia in 1998 and gained her DPhil in Human Genetics from Oxford University in 2003.
What’s the connection between dyslexia, left-handedness, schizophrenia and ADHD? According to Dr Silvia Paracchini of the University of St Andrews, it is probably something to do with the genes. And when we solve the biological puzzle of these common cognitive traits and disorders, we will also be closer to knowing how the human brain develops and how it evolved.
Following a recent trip to Hong Kong and Japan, supported by the Scottish Funding Council, Paracchini has also embarked on a journey to understand the cultural factors involved in the development of certain conditions, as well as understand the fundamental biology. In Japan, for example, the incidence of dyslexia is well below the global average of 5 – 10%, and awareness of dyslexia is relatively low. In Hong Kong and many other countries, there is still a stigma attached to left-handedness, and these cultural characteristics may disguise the true incidence of such common traits. By analysing the clinical data as well as studying the genes involved, a more accurate picture should therefore emerge, which can then be compared to the data already collected in other countries.
Genetic screening so far has only covered white European populations, and Paracchini's new project will extend this analysis to Asia, taking into account the fact that different languages (as well as different alphabets or character sets) have a major influence on the development of dyslexia; for example, there are also different patterns in the incidence of dyslexia between English and Italian speakers, even though they use the same alphabet. Part of the project, which is also supported by a Great Britain Sasakawa Foundation grant, will include setting up a network of clinicians, psychologists and epidemiologist, to collect behavioural and genetic data in Asia.
It is clear that many risk factors, both genetic and environmental, are involved in the development of dyslexia. Paracchini says that most of them (about 70%) are expected to be in our genes, and her research group has identified a handful of candidate genes. One of the most interesting features of these genes is that they seem to control the early phases of brain development through biological processes also involved in establishing our left and right asymmetries; so by studying these genes in detail, the researchers hope to understand better how the brain works and how it develops. Dyslexia provides us with a window into brain development in general,” Paracchini explains.
Left-handedness is one of the more curious topics being investigated by Paracchini, and one of the breakthroughs in this research happened “by accident,” when a new PhD student revisited clinical data left lying around in a drawer and discovered a link between dyslexia and left-handedness. There had been anecdotal evidence of links between left-handedness and dyslexia in families, but the new evidence seemed to confirm this. “The link, however, is more complex than expected,” says Paracchini.“While left-handedness does not have a higher incidence in people with dyslexia the genetic association with handedness appear to be specific to dyslexia. This association with handedness also points to the biological pathway involved in establishing our left/right body asymmetries (e.g., heart on the left and liver on the right).”
Paracchini has spent the last 14 years studying dyslexia. After graduating in Italy, she studied for her PhD in Human Genetics at Oxford, focusing on the development of genotyping methods and screening of large cohorts of data for genetic associations with prostate cancer and male infertility. This led to her research in dyslexia, mapping the first candidate gene in 2004, followed by the publication of a paper in 2006 which established the molecular mechanisms by which genetic variants in this gene could influence dyslexia. This research also found that the same genetic variants associated with dyslexia influence reading abilities in the general population.
“By using living models (human cells and zebrafish) to test the function of the genes identified from genetic screenings, we can understand what they are doing at molecular level,” says Paracchini. “Hopefully, by studying gene function, we can understand the connection between dyslexia and handedness. The genes we have identified so far have relatively small effects, so we still need to identify more candidate genes. That is why we are conducting larger genetic screenings. Ultimately, we hope this will lead to understanding the biological mechanisms behind different traits and disorders.”
To explore the phenomena further, Paracchini is also planning new research into the relationship between dyslexia and the arts, working with an artist based in Northern Ireland. There are also interesting links between brain symmetry, dyslexia and specific language impairment (SLI), as well as an apparent connection between left-handednness and the ability to recover from strokes – all of which will need to be investigated further.
Further progress, Paracchini explains, will depend on the technologies used to generate and analyse the genetic data, given the very large volumes involved and the challenge of making sense out of the data. This is a problem for human genetics in general, but dyslexia research presents additional caveats. “The diagnosis of dyslexia is not an exact science,” she says. “It also covers a spectrum, like autism. Dyslexia can be considered as the end of the scale of reading abilities observed across people, but it can be an arbitrary decision where to draw the line to decide who has dyslexia and who hasn’t.”
In the past, researchers focused on people with dyslexia only and excluded from their studies individuals with ADHD or language impairment, which often “co-occur” with dyslexia. “The rationale was to have a ‘pure’ population that would help to identify which genes contribute to dyslexia specifically. But this was probably a mistake,” says Paracchini.
There are clearly very interesting connections between all these different conditions, and understanding the connections between them will help reveal the inner secrets of the brain; thanks to genetic research and more in-depth analysis of clinical data. “We do not expect to identify genes which contribute to dyslexia, SLI or ADHD specifically, but rather to understand the role of genes during neurodevelopment,” Paracchini explains. “Not surprisingly, we are now observing that genes identified while studying one particular disorder quite often contribute to another condition.”
More “happy accidents” may also help in the search, as the history of science through the centuries has shown, but Paracchini will rely on purely scientific methods to make her next breakthrough.