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The genetics of synaesthesia
Po sted by Mo o n February 5, 20 0 9

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When Sir Francis Galton f irst described the peculiar habit of mind we now call synaesthesia, he noted that it of ten runs in f amilies. Modern techniques have conf irmed that the condition does indeed have a strong genetic component more than 40% of synaesthetes have a f irst-degree relative a parent, sibling or of f spring who also has synaesthesia, and f amilies of ten contain multiple synaesthetes. Synaesthesia is known to af f ect f emales more than males, and although the f emale predominance of the condition is now known to have been exaggerated, the condition is presumed to be linked to the X chromosome. A number of genetic studies also support the theory that a single gene is responsible f or synaesthesia, and that it is inherited in a

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dominant manner (in other words, just one copy of the gene, inherited f rom either parent, is suf f icient to cause it). Researchers f rom the University of Oxf ord have now conducted the f irst genome-wide search f or genes linked to the condition. In the American Journal of Human Genetics , they report the identif ication of a number of genes that are likely to be involved in auditory-visual synaesthesia, in which sounds are perceived as colours. T he study reveals probably that of other f orms is f ar more complex than previously thought. A group led by Julian Asher of the Wellcome Trust Centre f or Human Genetics, in collaboration with Simon Baron-Cohens group at Cambridge, studied 43 large f amilies, all of which include multiple members with auditory-visual synaesthesia. T hey recruited a total of 196 individuals, of which 121 were synaesthetes as conf irmed by a questionnaire designed to test f or the intensity and genuinesness of the synaesthetic experience.
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T he researchers obtained DNA samples f rom each participant, and analysed more than 400 microsatellites dispersed across all the chromosomes. Microsatellites consist of very short sequences which are repeated multiple times; each allele, or variant, of a given gene contains a unique number of repeats, and this number of ten varies between individuals. T hese sequences are theref ore of ten used to identif y genetic variation in humans, as dif f erent alleles of the same gene can be distinguished f rom one another. In this case, however, the researchers searched f or evidence of genetic linkage. By comparing the DNA samples f rom dif f erent generations of synaesthetes f rom the same f amily, they identif ied the microsatellites which are inherited together. Rather than identif ying specif ic genes, this analysis identif ied f our distinct chromosomal regions located on three dif f erent chromosomes, all containing genes of interest. T hese regions are known to contain genes associated with a variety of disorders, including autism, dyslexia and epilepsy. One of the candidate genes encodes the transcription f actor TBR1, which regulates the activity of a number of other genes, including reelin, a signalling protein that is critical f or the pro per development of the cerebral cortex; another plays a role in several dif f erent

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developmental processes, including axon guidance, the process by which extending neuronal processes f ind their correct destination; and a third candidate, a sodium channel protein called SCN2A, is involved in regulating the electrical actvity of nerve cells and has been implicated in epilepsy. T he region with the strongest linkage, which located on chromosome 2, is known to contain a gene associated with autism. Like synaesthesia, autism involves sensory and perceptual abnormalities, and autistics symptoms. Neuroimaging shows that the connections between the brains sensory pathways are both denser and more active in synaesthetes than in non-synaesthetes. T he condition is now viewed as being developmental in origin, and it is thought that newly-established connections, which would otherwise be pruned during development, remain in place, and perhaps become overactive. T he results of the new study theref ore f it nicely with current thinking about the neural bases of synaesthesia. Specif ic combinations of alleles of the identif ied candidate genes could f easibly lead to subtle changes in developmental processes which ultimately result in alterations in neural architecture and activity thought to be involved in the condition. As well as revealing the complexity of the genetics of synaesthesia, this study also shows that it can be inherited in a number of dif f erent ways (that is, by inheriting dif f erent combinations of alleles). T he eventual identif ication and proper classif ication of all the candidate genes will inevitably lead to a better understanding not only of synaesthesia and the other conditions with which they are associated, but also of their roles in cognition more generally. T he authors also suggest that advances in our knowledge of synaesthetic perceptions may even shed light on the neural basis of consciousness. Related: The neuropsychology of synaesthesia Tactile-emotion synaesthesia The sound of dots moving: A new form of synaesthesia Asher, J. E. et al (2009). A Whole-Genome Scan and Fine-Mapping Linkage Study of Auditoryof ten report synaesthesia-like

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Visual Synesthesia Reveals Evidence of Linkage to Chromosomes 2q24, 5q33, 6p12, and 12p12. Am. J. Hum. Genet. DOI: 10.1016/j.ajhg.2009.01.012.

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Karyn Romeis February 6, 2009

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#1

Im probably not qualified to make observations on this topic, but I persist in reading about it because I think I might be synaesthetic myself (Im not sure how one would go about being definitively diagnosed). Reading through your post, I get the distinct impression that we may all be synaesthetic at birth, but that the connections atrophy over time as only those correlations that fit with our cultural mores are encouraged and reinforced in much the same way as we teach our children manners by reward reinforcement of acceptable behaviours and active discouragement of the unacceptable. Before a child is able to verbalise their correlations between sounds and colours, the parents may inadvertently have begun the process of diminishing those connections just in the way they teach their children the vocabulary associated with shapes, numbers, sounds and colours. But lets say that the connections persist in sufficient strength until the child is able to move dreamily to a piece of music and say Blue! or clamp his hands over his ears and say Thorny! Unless synaesthesia is on the parents radar, they are likely to correct the childs pronouncement, because thats what good parents do. No dear. This is music, it doesnt have colours. Not thorny, dear. Loud. When I was a child, I didnt eat any cabbage- related vegetables because they all tasted greyish. I imagine when I said, I dont like this, its grey, I caused offence to whoever had cooked the vegetables! As I grew up, the nuanced shades of flavours became more defined and I realised that Brussels sprouts actually taste olive green, which I now enjoy. White cabbage still tastes grey, but it is a light grey, with a hint of light green about it and not unpleasant at all. Green cabbage tastes a deeper green with a hint of softening grey about it.

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However, most foods taste of colours for which I have no name because the texture and reflectiveness of the colour are as much a component of its definition as the colour itself.

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#2

This article interested me because I come from a family where many of us are both dyslexic and have varying forms of synaesthesia, and problems with language development. My daughter- in- law has none of these, so she recorded the colours we used for numbers up to ten and the days of the week for two generations. About three years later she repeated this and found that, not only had the colours not changed, but each person usually used the same phrases to describe the colours e.g. 3 is yellow, the colour of primroses whilst 6 is the yellow of daffodils. This result would make sense if the colours are hard- wired during development, and explain why siblings (including my twins) have different colours for the same numbers even though they used the same books etc as children?

night hawk808 February 6, 2009

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#3

I came across this post via genomewebs Daily Scan, and there synesthesia (the Americaniz ed spelling of it) was referred to as a disease. My response to this was the following: Synesthesia is a disease? Since when? Frankly, I would let someone cure me of my synesthesia about as quickly as Id let them cure me of my ability to taste sweetness or smell a rose blossom. I feel sorry for people who ARENT synesthetic, because they dont know what theyre missing. Really, if synesthesia is a disease just because it means I can do something most of the world cant, then as far as Im concerned, anyone who can play the piano or fix a jet engine is diseased, because I cant do either of those.

Dave Sherry February 9, 2009

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#4

The potential linkage of synesthesia to regulation of the reelin gene and other genes related to autism and epilepsy is extremely interesting. Reelin in particular not only regulates development of cerebral cortex but has key roles in the development and function of other regions of the brain including hippocampus and cerebellum. There is compelling evidence that Reelin can regulate the growth of neuronal processes and synapses in addition to its better known role in neuronal migration. One can imagine that interactions amongst a variety of genes could lead to localiz ed dysregulation of reelin and other genes involved in brain development in such a way as to establish novel circuits that would allow mixing and matching of sensory modalities. If reelin is a player in synesthesia a localiz ed change in its function might be expected since mutations that cause the global loss of reelin function in the developing brain cause Lissencephaly with Cerebellar Hypoplasia, a disastrous condition. This will be an interesting to story to follow as it develops. Im very glad I stumbled across this. Ill try to stumble back here more often. Thank you.

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Jude April 17, 2009

#5

So far as I know, Im the only one in the nuclear family I was born into that has it, and of my three children, only one has it and we disagree violently about what color something is. Ive always viewed it as yet another sign of my weirdness, but I have two friends at the moment (one an artist) who are fascinated by it. Until their fascination, I hadnt thought about it muchits just your worldview, part of who you are, so why analyz e it? But I suppose it is nice to learn at age 54 that others exist who are potentially as weird as I am.

Sylvia Lanz a May 6, 2009

#6

My sister and I as children both experienced words as having colors. We used to have discussions about what colors the words were, and we differed. We never thought there was something wrong with us, and I was happy to learn in the 1970s that there was a name for this. My mother had perfect pitch, and I am wondering if this could be a related mental phenomenon. For me, over the years, (I am now 70) the color association has faded somewhat, but I
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am so happy that I have had this multimedia experience. Im only sorry that I didnt have other synesthetic effects, such as musical notes associated with words.

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