Friday, February 20, 2009

[Yasmin_discussions] synaesthesia and genes

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By Alla Katsnelson
The genes that turn 'three' red
The first-ever genome-wide scan of synesthesia may illuminate how
genetics drives complex cognitive traits

[Published @ SCIENTIST on 5th February 2009 05:02 PM GMT]

Researchers have completed the first-ever genome-wide scan of
synesthesia, a condition in which sensory stimuli cross wires and
combine such that people "see" sounds or "taste" shapes, according to
a study published online today in the American Journal of Human Genetics.
Investigators at the Wellcome Trust Centre for Human Genetics at the
University of Oxford pinpointed four areas of the genome associated
with the disorder. Those regions contain genes that have been
associated with autism and dyslexia, as well as genes involved in
different aspects of brain development, and further analysis could
illuminate how genetics drives complex cognitive traits, the authors say.

"It's exciting that we have a study about the genetic basis of
synesthesia -- finally," said Noam Sagiv, a cognitive neuroscientist
at Brunel University in the UK, who was not involved in the research.
Until now "we've just been guessing," he said, by "using data based on
prevalence estimates."

Francis Galton, best known as one of the founders of eugenics, first
pointed out in the 19th century that synesthesia runs in families,
suggesting it has a genetic component. "Based on pedigree analysis,
many people thought that [synesthesia] was a simple Mendelian
disorder," said Julian Asher, now at Imperial College, London, the
study's lead author and himself a synesthete. The study, however,
demonstrated that the condition is multigenic. Which makes sense,
Asher noted: "The clinical phenotype is so complex, it's hard to
believe all of that can be caused by a single gene."

Consequently, "now we're looking at gene-gene interactions, with
multiple genes contributing," Asher said.

The condition comes in several forms, but Asher and his colleagues
conducted their genetic analysis on individuals with what's known as
known as auditory-visual synesthesia -- the classical form, in which
individuals strongly associate sounds with specific colors.

The region of the genome most strongly linked to synesthesia was on
chromosome 2, and has also been strongly linked to autism. That
doesn't mean that the two conditions are related, per se, explained Ed
Hubbard, a cognitive neuroscientist at Vanderbilt University in
Tennessee who was not involved in the study. Instead, the common gene
or genes are likely "more generally involved in how the brain gets built."

The study also pulled out a region on chromosome 6 that contains genes
linked to dyslexia -- especially interesting, "seeing as phonemes [the
units of sound in language] and letters are two of the strongest
synesthetic triggers," Asher said. One possibility, he said, is that
mutations in those genes lead people to process those stimuli
differently. "Maybe some people [with those mutations] end up with
dyslexia, and some with synesthesia."

The genetic analysis also dispelled the long-held assumption that
synesthesia was an X-linked disorder, an idea that stemmed from the
fact that researchers had never before seen synesthetic fathers who
had synesthetic sons. In their subject pool, the researchers
identified two cases of such male-to-male transmission, demonstrating
that the condition is almost certainly autosomal.

Asher and his colleagues are following up their study with
higher-density screening, to narrow down their list of candidate
genes. "Next, we want to home in on what these genes are and what they
do," he said.

At least two other labs, one at Baylor College of Medicine in Houston,
and the other Trinity College, Dublin, have been working on similar
genetic studies, but the subject database of those groups differs from
that used in the current study, said Hubbard. The Irish group includes
fewer families, but with more individuals from each family, and the
Houston group focuses on people with a form of the condition called
sequence-to-color synesthesia.

The differences in the populations "could make a huge difference,"
said Sagiv. Asher and his colleagues were wise to choose a very
specific population of synesthetes for the field's first genetic
study, he said, but broadening the inclusion criteria to different
forms of the disorder may identify additional genes.

Hubbard agreed that the results of all three genetic studies together
will further flesh out the picture. "Once we start to identify genes
that are involved, we can start to look at what function they play in
a mouse or monkey brain," he said, and then "come up with ways of
studying what they do experimentally" in animal models.

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