A whole-genome scan and fine-mapping linkage study of auditory-visual synesthesia reveals rvidence of linkage to chromosomes 2q24, 5q33, 6p12, and 12p12

American Journal of Human Genetics

Volumn 84, Issue 2, 2008, Pages 279-285

  Asher, Julian E ^a,b   Lamb, Janine A ^c   Brocklebank, Denise ^a   Cazier, Jean Baptiste ^a   Maestrini, Elena ^d   Addis, Laura ^a   Sen, Mallika ^a   Baron Cohen, Simon ^b   Monaco, Anthony P ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

^d UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; AUDITORY VISUAL SYNESTHESIA; CELL HETEROGENEITY; CHROMOSOME 12P; CHROMOSOME 2Q; CHROMOSOME 5Q; CHROMOSOME 6P; CHROMOSOME IDENTIFICATION; GENE FUNCTION; GENE LOCATION; GENE MAPPING; GENETIC ASSOCIATION; GENETIC LINKAGE; GENOME ANALYSIS; HUMAN; INHERITANCE; MAJOR CLINICAL STUDY; MALE; MICROSATELLITE MARKER; NONPARAMETRIC TEST; PRIORITY JOURNAL; SENSORY DYSFUNCTION; SEX DIFFERENCE; X CHROMOSOME; CHROMOSOME 12; CHROMOSOME 2; CHROMOSOME 5; CHROMOSOME 6; CHROMOSOME MAP; FEMALE; GENETIC MARKER; GENETIC PREDISPOSITION; GENETICS; HALLUCINATION; HUMAN GENOME; METHODOLOGY; SEXUAL DEVELOPMENT;

CHROMOSOME MAPPING; CHROMOSOMES, HUMAN, PAIR 12; CHROMOSOMES, HUMAN, PAIR 2; CHROMOSOMES, HUMAN, PAIR 5; CHROMOSOMES, HUMAN, PAIR 6; FEMALE; GENETIC MARKERS; GENETIC PREDISPOSITION TO DISEASE; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; HALLUCINATIONS; HUMANS; MALE; SEX CHARACTERISTICS;

EID: 62649125833     PISSN: 00029297     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ajhg.2009.01.012     Document Type: Article

References (66)

1. Barnett, K., Newell, F., Finucane, C., Asher, J., Corvin, A., and Mitchell, K. (2008). Familial patterns and the origins of individual differences in synaesthesia. Cortex 106, 871-893.
2. Baron-Cohen, S., Burt, L., Smith-Laittan, F., Harrison, J., and Bolton, P. (1996). Synaesthesia: Prevalence and familiality. Perception 25 1073-1079.
3. Simner, J.,Mulvenna, C., Sagiv, N., Tsakanikos, E.,Witherby, S.A., Fraser, C., Scott, K., andWard, J. (2006). Synaesthesia: The prevalence of atypical cross-modal experiences. Perception 35, 1024-1033.
4. Baron-Cohen, S., Wyke, M.A., and Binnie, C. (1987). Hearing words and seeing colours: An experimental investigation of a case of synaesthesia. Perception 16, 761-767.
5. Ward, J., Huckstep, B., and Tsakanikos, E. (2006). Soundcolour synaesthesia: To what extent does it use cross-modal mechanisms common to us all? Cortex 42, 264-280.
6. Mattingley, J.B., Rich, A.N., Yelland, G., and Bradshaw, J.L. (2001). Unconscious priming eliminates automatic binding of colour and alphanumeric form in synaesthesia. Nature 410, 580-582.
7. Ramachandran, V.S., and Hubbard, E.M. (2001). Psychophysical investigations into the neural basis of synaesthesia. Proc. R. Soc. Lond. B. Biol. Sci. 268, 979-983.
8. Green, J.A., and Goswami, U. (2007). Synesthesia and number cognition in children. Cognition 106, 463-473.
9. Luria, A. (1968). The Mind of a Mnemonist (Cambridge, Massachusetts: Harvard University Press).
10. Smilek, D., Dixon, M.J., Cudahy, C., and Merikle, P.M. (2002). Synesthetic color experiences influence memory. Psychol. Sci. 13, 548-552.
11. Yaro, C., and Ward, J. (2007). Searching for Shereshevskii: What is superior about the memory of synaesthetes? Q. J. Exp. Psychol. 60, 681-695.
12. Rizzo, M., and Eslinger, P.J. (1989). Colored hearing synesthesia: An investigation of neural factors. Neurology 39, 781-784.
13. Glicksohn, J., Steinbach, I., and Elimalach-Malmilyan, S. (1999). Cognitive dedifferentiation in eidetics and synaesthesia: Hunting for the ghost once more. Perception 28, 109-120.
14. Nunn, J.A., Gregory, L.J., Brammer, M., Williams, S.C., Parslow, D.M., Morgan, M.J., Morris, R.G., Bullmore, E.T., Baron-Cohen, S., and Gray, J.A. (2002). Functional magnetic resonance imaging of synesthesia: Activation of V4/V8 by spoken words. Nat. Neurosci. 5, 371-375.
15. Rouw, R., and Scholte, H.S. (2007). Increased structural connectivity in grapheme-color synesthesia. Nat. Neurosci. 10, 792-797.
16. Galton, F. (1883). Inquiries into Human Faculty and its Development (London: Macmillan).
17. Bailey, M., and Johnson, K. (1997). Synaesthesia: Is a genetic analysis feasible? In Synaesthesia: Classic and Contemporary Readings, S. Baron-Cohen and J. Harrison, eds. (Oxford: Blackwell), pp. 182-207.
18. Ward, J., and Simner, J. (2005). Is synaesthesia an X-linked dominant trait with lethality in males? Perception 34, 611-623.
19. Asher, J.E., Aitken, M.R., Farooqi, N., Kurmani, S., and Baron-Cohen, S. (2006). Diagnosing and phenotyping visual synaesthesia: A preliminary evaluation of the revised test of genuineness (TOG-R). Cortex 42, 137-146.
20. Weeks, D., Ott, J., and Lathrop, G. (1990). SLINK: A general simulation program for linkage analysis. Am. J. Hum. Genet. 47, A204.
21. Rozen, S., and Skaletsky, H. (2000). Primer3 on the WWW for general users and for biologist programmers. Methods and Protocols: Methods in Molecular Biology (Totowa, NJ: Humana Press), pp. 365-386.
22. Young, A. (1995) Genetic Analysis System, version 1.4. Internet: ftpwelloxacuk.
23. O'Connell, J.R., andWeeks, D.E. (1998). PedCheck: A program for identification of genotype incompatibilities in linkage analysis. Am. J. Hum. Genet. 63, 259-266.
24. Kong, A., and Cox, N.J. (1997). Allele-sharing models: LOD scores and accurate linkage tests. Am. J. Hum. Genet. 61, 1179-1188.
25. Abecasis, G.R., Cherny, S.S., Cookson,W.O., and Cardon, L.R. (2002). Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30, 97-101.
26. Whittemore, A.S., and Halpern, J. (1994). A class of tests for linkage using affected pedigree members. Biometrics 50, 118-127.
27. Lander, E., and Kruglyak, L. (1995). Genetic dissection of complex traits: Guidelines for interpreting and reporting linkage results. Nat. Genet. 11, 241-247.
28. Paracchini, S., Scerri, T., and Monaco, A.P. (2007). The genetic lexicon of dyslexia. Annu. Rev. Genomics Hum. Genet. 8, 57-79.
29. Newbury, D.F., Bishop, D.V., and Monaco, A.P. (2005). Genetic influences on language impairment and phonological shortterm memory. Trends Cogn. Sci. 9, 528-534.
30. Fisher, S.E., Vargha-Khadem, F., Watkins, K.E., Monaco, A.P., and Pembrey, M.E. (1998). Localisation of a gene implicated in a severe speech and language disorder. Nat. Genet. 18, 168-170.
31. Martin, C.L., and Ledbetter, D.H. (2007). Autism and cytogenetic abnormalities: Solving autism one chromosome at a time. Curr. Psychiatry Rep. 9, 141-147.
32. IMGSAC. (2001). A genomewide screen for autism: Strong evidence for linkage to chromosomes 2q, 7q, and 16p. Am. J. Hum. Genet. 69, 570-581.
33. Harrison, J., and Hare, D.J. (2004). Brief report: Assessment of sensory abnormalities in people with autistic spectrum disorders. J. Autism Dev. Disord. 34, 727-730.
34. Ashwin, E., Ashwin, C., Rhydderch, D., Howells, J., and Baron-Cohen, S. (2008). Eagle-Eyed Visual Acuity: An experimental investigation of enhanced perception in autism. Biol. Psychiatry 65, 17-21.
35. Belmonte, M.K., Allen, G., Beckel-Mitchener, A., Boulanger, L.M., Carper, R.A., and Webb, S.J. (2004). Autism and abnormal development of brain connectivity. J. Neurosci. 24, 9228-9231.
36. Kemner, C., Verbaten, M.N., Cuperus, J.M., Camfferman, G., and van Engeland, H. (1995). Auditory event-related brain potentials in autistic children and three different control groups. Biol. Psychiatry 38, 150-165.
37. Courchesne, E., Redcay, E., Morgan, J.T., and Kennedy, D.P. (2005). Autism at the beginning: Microstructural and growth abnormalities underlying the cognitive and behavioral phenotype of autism. Dev. Psychopathol. 17, 577-597.
38. Baron-Cohen, S., Bor, D., Billington, J., Asher, J., Wheelwright, S., and Ashwin, C. (2007). Savant memory in a man with colour form-number synaesthesia and Asperger Syndrome. J. Conscious. Stud. 14, 237-252.
39. Bulfone, A., Smiga, S.M., Shimamura, K., Peterson, A., Puelles, L., and Rubenstein, J.L. (1995). T-brain-1: A homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex. Neuron 15, 63-78.
40. Hsueh, Y.P., Wang, T.F., Yang, F.C., and Sheng, M. (2000). Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature 404, 298-302.
41. Hevner, R.F., Miyashita-Lin, E., and Rubenstein, J.L. (2002). Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant mice: Evidence that cortical and thalamic axons interact and guide each other. J. Comp. Neurol. 447, 8-17.
42. Hevner, R.F., Shi, L., Justice, N., Hsueh, Y., Sheng, M., Smiga, S., Bulfone, A., Goffinet, A.M., Campagnoni, A.T., and Rubenstein, J.L. (2001). Tbr1 regulates differentiation of the preplate and layer 6. Neuron 29, 353-366.
43. Whitaker,W.R., Clare, J.J., Powell, A.J., Chen, Y.H., Faull, R.L., and Emson, P.C. (2000). Distribution of voltage-gated sodium channel alpha-subunit and beta-subunit mRNAs in human hippocampal formation, cortex, and cerebellum. J. Comp. Neurol. 422, 123-139.
44. Whitaker, W.R., Faull, R.L., Waldvogel, H.J., Plumpton, C.J., Emson, P.C., and Clare, J.J. (2001). Comparative distribution of voltage-gated sodium channel proteins in human brain. Brain Res. Mol. Brain Res. 88 37-53.
45. Escayg, A., MacDonald, B.T., Meisler, M.H., Baulac, S., Huberfeld, G., An-Gourfinkel, I., Brice, A., LeGuern, E., Moulard, B., Chaigne, D., et al. (2000). Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nat. Genet. 24, 343-345.
46. Wallace,R.H., Scheffer, I.E.,Barnett, S., Richards,M., Dibbens, L., Desai, R.R., Lerman-Sagie,T., Lev, D.,Mazarib,A.,Brand,N., et al. (2001). Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet. 68, 859-865.
47. Berkovic, S.F.,Heron, S.E., Giordano, L., Marini, C., Guerrini, R., Kaplan, R.E., Gambardella, A., Steinlein, O.K., Grinton, B.E., Dean, J.T., et al. (2004). Benign familial neonatal-infantile seizures: Characterization of a new sodium channelopathy. Ann. Neurol. 55, 550-557.
48. Herlenius, E., Heron, S.E., Grinton, B.E., Keay, D., Scheffer, I.E., Mulley, J.C., and Berkovic, S.F. (2007). SCN2A mutations and benign familial neonatal-infantile seizures: The phenotypic spectrum. Epilepsia 48, 1138-1142.
49. McCormick, D.A., and Contreras, D. (2001). On the cellular and network bases of epileptic seizures. Annu. Rev. Physiol. 63, 815-846.
50. Bacchelli, E., Blasi, F., Biondolillo, M., Lamb, J.A., Bonora, E., Barnby, G., Parr, J., Beyer, K.S., Klauck, S.M., Poustka, A., et al. (2003). Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene. Mol. Psychiatry 8, 916-924.
51. Weiss, L.A., Escayg, A.,Kearney, J.A., Trudeau, M., MacDonald, B.T., Mori, M., Reichert, J., Buxbaum, J.D., and Meisler, M.H. (2003). Sodium channels SCN1A, SCN2A and SCN3A in familial autism. Mol. Psychiatry 8 186-194.
52. Zhang, Y., Iwasaki, H., Wang, H., Kudo, T., Kalka, T.B., Hennet, T., Kubota, T., Cheng, L., Inaba, N., Gotoh, M., et al. (2003). Cloning and characterization of a new human UDP-N-acetyl-alpha-D-galactosamine:pOlypeptide N-acetylgalactosaminyltransferase, designated pp-GalNAc-T13, that is specifically expressed in neurons and synthesizes GalNAc alpha-serine/ threonine antigen. J. Biol. Chem. 278, 573-584.
53. Brockschnieder, D., Sabanay, H., Riethmacher, D., and Peles, E. (2006). Ermin, a myelinating oligodendrocyte-specific protein that regulates cell morphology. J. Neurosci. 26, 757-762.
54. Fisher, S.E., Francks, C., Marlow, A.J., MacPhie, I.L., Newbury, D.F., Cardon, L.R., Ishikawa-Brush, Y., Richardson, A.J., Talcott, J.B., Gayan, J., et al. (2002). Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. Nat. Genet. 30, 86-91.
55. Kaplan, D.E., Gayan, J., Ahn, J., Won, T.W., Pauls, D., Olson, R.K., DeFries, J.C., Wood, F., Pennington, B.F., Page, G.P., et al. (2002). Evidence for linkage and association with reading disability on 6p21.3-22. Am. J. Hum. Genet. 70, 1287-1298.
56. Paracchini, S., Thomas, A., Castro, S., Lai, C., Paramasivam, M., Wang, Y., Keating, B.J., Taylor, J.M., Hacking, D.F., Scerri, T., et al. (2006). The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration. Hum. Mol. Genet. 15, 1659-1666.
57. Meng, H., Smith, S.D., Hager, K., Held, M., Liu, J., Olson, R.K., Pennington, B.F., DeFries, J.C., Gelernter, J., O'Reilly-Pol, T., et al. (2005). DCDC2 is associated with reading disability and modulates neuronal development in the brain. Proc. Natl. Acad. Sci. USA 102, 17053-17058.
58. Suzuki, T., Delgado-Escueta, A.V., Aguan, K., Alonso, M.E., Shi, J., Hara, Y., Nishida, M., Numata, T., Medina, M.T., Takeuchi, T., et al. (2004). Mutations in EFHC1 cause juvenile myoclonic epilepsy. Nat. Genet. 36, 842-849.
59. Shimizu, E., Tang, Y.P., Rampon, C., and Tsien, J.Z. (2000). NMDAreceptor-dependent synaptic reinforcement as a crucial process for memory consolidation. Science 290, 1170-1174.
60. Tang,Y.P., Shimizu, E., Dube, G.R.,Rampon,C., Kerchner, G.A., Zhuo, M., Liu, G., and Tsien, J.Z. (1999). Genetic enhancement of learning and memory in mice. Nature 401, 63-69.
61. McCauley, J.L., Li, C., Jiang, L., Olson, L.M., Crockett, G., Gainer, K., Folstein, S.E., Haines, J.L., and Sutcliffe, J.S. (2005). Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates. BMC Med. Genet. 6, 1.
62. Quinn, C.C., Gray, G.E., and Hockfield, S. (1999). A family of proteins implicated in axon guidance and outgrowth. J. Neurobiol. 41, 158-164.
63. Choi, Y.L., Kim, C.J., Matsuo, T., Gaetano, C., Falconi, R., Suh, Y.L., Kim, S.H., Shin, Y.K., Park, S.H., Chi, J.G., et al. (2005). HUlip, a human homologue of unc-33-like phosphoprotein of Caenorhabditis elegans; Immunohistochemical localization in the developing human brain and patterns of expression in nervous system tumors. J. Neurooncol. 73 19-27.
64. Levitin, D.J., Cole, K., Lincoln, A., and Bellugi, U. (2005). Aversion, awareness, and attraction: Investigating claims of hyperacusis in the Williams syndrome phenotype. J. Child Psychol. Psychiatry 46, 514-523.
65. Simner, J., Ward, J., Lanz, M., Ashok, J., Noona, K., Glover, L., and Oakley, D. (2005). Non-random associations of graphemes to colours in synaesthetic and normal populations. Cogn. Neuropsychol. 22, 1069-1085.
66. Gray, J., Chopping, S., Nunn, J., Parslow, D., Gregory, L., Williams, S., Brammer, M., and Baron-Cohen, S. (2002). Implications of synaesthesia for functionalism. J. Conscious. Stud. 9, 5-31.