Genetics of synesthesia

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The genetic mechanism of synesthesia has long been debated, with researchers previously claiming it was a single X-linked trait due to seemingly higher prevalence in women and no evidence of male-male transmission [1] This is where the only synesthetic parent is male and the male child has synesthesia, [2] [3] meaning that the trait cannot be solely linked to the X chromosome.

The Mendelian nature of the trait was further disproven when case studies showed that the Phenotype of synesthesia could be differentially expressed in monozygotic (genotypically identical) twins [4] While both twins had the same genome with the potential for phenotypic expression of synesthesia, only one had documented synesthesia. Therefore, the condition is now thought to be oligogenic, with Locus heterogeneity and multiple forms of inheritance, and expression, [5] implying that synesthesia is determined by more than one gene, more than one location in those genes, and a complex mode of inheritance. Several full genome linkage scans have shown particular areas of the genome whose inheritance seem to correlate with the inheritance of synesthesia.

Using the LOD score which describes the likelihood that two genes are near each other on a chromosome, and thus will be inherited together, areas of strong or suggestive linkage with inheritance of synesthesia were found. [6] The area with the highest LOD score in the genome of an individual with auditory-visual synesthesia has been shown to be linked with autism as well, [7] another disorder with sensory and perceptual abnormalities. Other regions of linkage include genes that are related to the development of the cerebral cortex (TBR1), dyslexia, and apoptosis (EFHC1), [8] the last of which could be potentially related to the retention of the neonatal synesthetic pathways in the universal synesthesia/pruning hypothesis. This hypothesis posits that every person is born a synesthete and the ‘extra’ connections are pruned during normal neurodevelopment in non-synesthetes, and not pruned in synesthetes. [9]

More potential support for that hypothesis comes from another region identified with strong linkage, which contains a gene (DPYSL3) which is involved in axonal growth, neuroplasticity, and neuronal differentiation. [10] Additionally, this gene is not expressed in the adult brain but is highly expressed in the late-fetal and early post-natal brain and spinal cord, providing more support for a universal “neonatal synesthesia” that is pruned away through natural development. [11]

Another genome scan [12] revealed a different area of linkage for an individual with colored sequence synesthesia: one which associates days of the week with colors. In that individual, the linked region contained genes that produces proteins important for intercellular communication (GABARAPL2), genes that are involved in brain development (NDRG4), genes linked to neuron myelination (PLLP), genes that produce enzymes involved in neuronal pruning (KATNB1), genes that produce Apoptosis inhibitors expressed in fetal brains (CIAPIN1), and genes that produce proteins that have differential expression in individuals with schizophrenia (GNAO1).

Due to the prevalence of synesthesia among the first-degree relatives of synesthetes, [13] there is evidence that synesthesia might have a genetic basis, however the monozygotic twins case studies indicate there is an epigenetic component. Synesthesia might also be an oligogenic condition, with Locus heterogeneity, multiple forms of inheritance (including Mendelian in some cases), and continuous variation in gene expression.

See also

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Genetics Science of genes, heredity, and variation in living organisms

Genetics is a branch of biology concerned with the study of genes, genetic variation, and heredity in organisms.

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In biology, epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic basis for inheritance. Epigenetics most often involves changes that affect gene activity and expression, but the term can also be used to describe any heritable phenotypic change. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors, or be part of normal development. The standard definition of epigenetics requires these alterations to be heritable in the progeny of either cells or organisms.

Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. In other words, the nearer two genes are on a chromosome, the lower the chance of recombination between them, and the more likely they are to be inherited together. Markers on different chromosomes are perfectly unlinked.

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Human genetics

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Synesthesia is a neurological condition in which two or more bodily senses are coupled. For example, in a form of synesthesia known as Grapheme → color synesthesia, letters or numbers may be perceived as inherently colored. In another, called number → form synesthesia, numbers are automatically and consistently associated with locations in space. In yet another form of synesthesia, called ordinal linguistic personification, either numbers, days of the week, or months of the year evoke personalities. In other forms of synesthesia, music and other sounds may be perceived as colored or having particular shapes. Recent research has begun to explore the neural basis of these experiences, drawing both on neuroscientific principles and on functional neuroimaging data.

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Chromesthesia Sound to color synesthesia

Chromesthesia or sound-to-color synesthesia is a type of synesthesia in which sound involuntarily evokes an experience of color, shape, and movement. Individuals with sound-color synesthesia are consciously aware of their synesthetic color associations/perceptions in daily life. Synesthetes that perceive color while listening to music, experience the colors in addition to the normal auditory sensations. The synesthetic color experience supplements, but does not obscure real, modality-specific perceptions. As with other forms of synesthesia, individuals with sound-color synesthesia perceive it spontaneously, without effort, and as their normal realm of experience. Chromesthesia can be induced by different auditory experiences, such as music, phonemes, speech, and/or everyday sounds.

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Synesthesia Neurological condition involving the crossing of senses

Synesthesia or synaesthesia is a perceptual phenomenon in which stimulation of one sensory or cognitive pathway leads to involuntary experiences in a second sensory or cognitive pathway. People who report a lifelong history of such experiences are known as synesthetes (sin-es-the-t). Awareness of synesthetic perceptions varies from person to person. In one common form of synesthesia, known as grapheme–color synesthesia or color–graphemic synesthesia, letters or numbers are perceived as inherently colored. In spatial-sequence, or number form synesthesia, numbers, months of the year, or days of the week elicit precise locations in space, or may appear as a three-dimensional map. Synesthetic associations can occur in any combination and any number of senses or cognitive pathways.

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References

  1. ↑ Smilek, Daniel; Moffat, Barbara A; Pasternak, J; White, B.N.; Dixon, M.J.; Merikle, P.M. (October 1, 2002). "Synaesthesia: a case study of discordant monozygotic twins". Neurocase. 8 (4): 338–342. doi:10.1076/neur.8.3.338.16194. PMID   12221147.
  2. ↑ Ward, Jamie; Simner, Julia (May 2005). "Is synaesthesia an X-linked dominant trait with lethality in males?" (PDF). Perception. 34 (5): 611–623. doi:10.1068/p5250. PMID   15991697.
  3. ↑ Simner, Julia; Carmichael, Duncan A. (2015). "Is synaesthesia a dominantly female trait?". Cognitive Neuroscience. 6 (2–3): 68–76. doi:10.1080/17588928.2015.1019441. PMC   4566887 . PMID   25732702.
  4. ↑ Smilek, Daniel; Moffat, Barbara A; Pasternak, J; White, B.N.; Dixon, M.J.; Merikle, P.M. (October 1, 2002). "Synaesthesia: a case study of discordant monozygotic twins". Neurocase. 8 (4): 338–342. doi:10.1076/neur.8.3.338.16194. PMID   12221147.
  5. ↑ Asher, Julian E.; Lamb, Janine A.; Brocklebank, Denise; Cazier, Jean-Baptiste; Maestrini, Elena; Addis, Laura; Sen, Mallika; Baron-Cohen, Simon; Monaco, Anthony P. (13 February 2009). "A Whole-Genome Scan and Fine-Mapping Linkage Study of Auditory-Visual Synesthesia Reveals Evidence of Linkage to Chromosomes 2q24, 5q33, 6p12, and 12p12". The American Journal of Human Genetics. 84 (2): 279–285. doi:10.1016/j.ajhg.2009.01.012. PMC   2668015 . PMID   19200526.
  6. ↑ Asher, Julian E.; Lamb, Janine A.; Brocklebank, Denise; Cazier, Jean-Baptiste; Maestrini, Elena; Addis, Laura; Sen, Mallika; Baron-Cohen, Simon; Monaco, Anthony P. (13 February 2009). "A Whole-Genome Scan and Fine-Mapping Linkage Study of Auditory-Visual Synesthesia Reveals Evidence of Linkage to Chromosomes 2q24, 5q33, 6p12, and 12p12". The American Journal of Human Genetics. 84 (2): 279–285. doi:10.1016/j.ajhg.2009.01.012. PMC   2668015 . PMID   19200526.
  7. ↑ Palferman, Sarah; Matthews, Nicola; Turner, Michelle; Moore, J.; Hervas, Amaia; Aubin, Ann (September 2001). "A genomewide screen for autism: strong evidence for linkage to chromosomes 2q, 7q, and 16p". The American Journal of Human Genetics. 69 (3): 570–581. doi:10.1086/323264. PMC   1235486 . PMID   11481586.
  8. ↑ Asher, Julian E.; Lamb, Janine A.; Brocklebank, Denise; Cazier, Jean-Baptiste; Maestrini, Elena; Addis, Laura; Sen, Mallika; Baron-Cohen, Simon; Monaco, Anthony P. (13 February 2009). "A Whole-Genome Scan and Fine-Mapping Linkage Study of Auditory-Visual Synesthesia Reveals Evidence of Linkage to Chromosomes 2q24, 5q33, 6p12, and 12p12". The American Journal of Human Genetics. 84 (2): 279–285. doi:10.1016/j.ajhg.2009.01.012. PMC   2668015 . PMID   19200526.
  9. ↑ Kadosh, Roi Cohen; Avishai, Henik; Walsh, Vincent (5 February 2009). "Synaesthesia: learned or lost?". Developmental Science. 12 (3): 484–491. doi:10.1111/j.1467-7687.2008.00798.x. PMID   19371373.
  10. ↑ Quinn, Christopher C.; Gray, Grace E.; Hockfield, Susan (October 1999). "A family of proteins implicated in axon guidance and outgrowth". Journal of Neurobiology. 41 (1): 158–64. doi:10.1002/(SICI)1097-4695(199910)41:1<158::AID-NEU19>3.0.CO;2-0. PMID   10504203.
  11. ↑ Kadosh, Roi Cohen; Avishai, Henik; Walsh, Vincent (5 February 2009). "Synaesthesia: learned or lost?". Developmental Science. 12 (3): 484–491. doi:10.1111/j.1467-7687.2008.00798.x. PMID   19371373.
  12. ↑ Tomson, Steffie N.; Avidan, Nili; Lee, Kwanghyuk; Sarma, Anand K.; Tushe, Rejnal; Milewicz, Dianna M.; Bray, Molly; Leal, Suzanne M.; Eagleman, David M. (8 April 2011). "The genetics of colored sequence synesthesia: Suggestive evidence of linkage to 16q and genetic heterogeneity for the condition". Behavioural Brain Research. 223 (1): 48–52. doi:10.1016/j.bbr.2011.03.071. PMC   4075137 . PMID   21504763.
  13. ↑ Baron-Cohen, Simon; Burt, Lucy; Smith-Laittan, Fiona; Harrison, John; Bolton, Patrick (1 September 1996). "Synaesthesia: prevalence and familiality". Perception. 25 (9): 1073–1079. doi:10.1068/p251073. PMID   8983047.
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