Some genes. Genes and language, Part VI: Dan Dediu. Dan Dediu

Transcription

1 Genes and language, Part VI: Some genes DGFS Summer School 2013 Berlin 26th 30th of August, 2013 Language and Genetics Max Planck Institute for Psycholinguistics Nijmegen The Netherlands 1

2 Overview Part VI Hearing loss (TECTA, 12S rrna, GJB2 and GJB6, MYO15A) Stuttering (GNPTAB, GNPTG, NAGPA) Dyslexia (ROBO1, KIAA0319) Brain growth & development/microcephaly (ASPM, MCPH1) So, how do genes influence language? Overview 12

3 Genetic mechanisms in hearing loss Many types of hearing loss Drugs Infections Aging Acquired Head injury Noise Hearing loss Congenital Prenatal infections Genetic mechanisms in hearing loss Genetics 13

4 Genetic mechanisms in hearing loss Many types of hearing loss genetic role Drugs Infections Aging Acquired Head injury Noise Hearing loss Congenital Prenatal infections Genetic mechanisms in hearing loss Genetics 14

5 Some examples: TECTA hearing loss 15

6 Some examples: TECTA Tectorial membrane: collagen hearing loss 16

7 Some examples: TECTA Tectorial membrane: collagen non-collagenous proteins α-tectorin TECTA gene (11q23.3) hearing loss 17

8 Some examples: TECTA Tectorial membrane: collagen non-collagenous proteins mu tat ion s α-tectorin TECTA gene (11q23.3) hearing loss 18

9 Some examples: TECTA Tectorial membrane: collagen non-collagenous proteins α-tectorin DFNA12 - dominant TECTA gene hearing loss 19

10 Some examples: TECTA Tectorial membrane: collagen non-collagenous proteins α-tectorin DFNA12 - dominant DFNB21 - recessive TECTA gene hearing loss 1

11 Some examples: mitochondrial 12S rrna hearing loss 1

12 Some examples: mitochondrial 12S rrna hearing loss 1

13 Some examples: mitochondrial 12S rrna Own genetic code own translation machinery own ribosomes Sm rib all s oso ub ma uni lr t NA hearing loss 1

14 Some examples: mitochondrial 12S rrna Mitochondria ancient bacteria (endosymbiotic theory) hearing loss 1

15 Some examples: mitochondrial 12S rrna Mitochondria ancient bacteria (endosymbiotic theory) mitochondrial ribosomes are very similar to bacterial ribosomes Mutations (e.g. A1555G) even more similar modifiers hearing loss 1

16 Congenital non-syndromic deafness Many loci (e.g., Autosomal dominant: DFNAnn (~25) 0% 100% hearing loss 50% 75% 100% 100% 1

17 Congenital non-syndromic deafness Many loci (e.g., Autosomal dominant: DFNAnn, recessive: DFNBnn (~40) hearing loss 0% 0% 25% 0% 50% 100% 1

18 DFNB1A/B (GJB2 and GJB6) Autosomal recessive 13q12.11 GJB2 (Gap junction beta-2; Connexin 26) and GJB6 (Gap junction beta-6; Connexin 30) hearing loss 1

19 DFNB1A/B (GJB2 and GJB6) Autosomal recessive 13q12.11 GJB2 (Gap junction beta-2; Connexin 26) and GJB6 (Gap junction beta-6; Connexin 30) GJB2: ~90 mutations non-syndromic deafness other mutations: syndromes (skin + deafness) GJB6: some mutations non-syndromic deafness other mutations: skin disorders potassium levels in the inner ear? hearing loss 1

20 DFNB3 (MYO15A) Autosomal recessive 17p11.2 MYO15A (unconventional myosin-15; myosin XVa) sterocilia hearing loss 12

21 DFNB3 (MYO15A) Autosomal recessive 17p11.2 MYO15A (unconventional myosin-15; myosin XVa) hearing loss EPS8 transport sterocilia interaction 12

22 Some examples: stuttering Digestive enzymes stuttering 12

23 Some examples: stuttering GNPTG (chr 16) GNPT 3 subunits (α, β, and γ) GNPTAB (chr 12) Genome-wide linkage in many Pakistani families mutation in GNPTAB + stuttering identification of mutations in GNPTG and NAGPA 12

24 Some examples: dyslexia Linkage in a Finnish family with severe dyslexia + Non-related patient dyslexia 12

25 Some examples: dyslexia Linkage in a Finnish family with severe dyslexia + Non-related patient ROBO1 gene on chromosome 3 dyslexia 12

26 Some examples: dyslexia Linkage in a Finnish family with severe dyslexia + Non-related patient ROBO1 gene on chromosome 3 Association with NWR in normal population dyslexia 12

27 Some examples: dyslexia Linkage in a Finnish family with severe dyslexia + Non-related patient ROBO1 gene on chromosome 3 Association with NWR in normal population Interaural interaction auditory pathways in dyslexic subjects More ROBO1 expression dyslexia 12

28 Some examples: dyslexia Linkage in a Finnish family with severe dyslexia + Non-related patient ROBO1 gene on chromosome 3 Association with NWR in normal population Interaural interaction auditory pathways in dyslexic subjects ROBO1: axonal midline crossing dyslexia 12

29 Some examples: KIAA0319 Susceptibility gene for dyslexia (association) Neuronal migration/cell adhesion Cortex Time dyslexia 12

30 Brain growth & development: ASPM & MCP1 Neurogenesis and migration dyslexia 13

31 Brain growth & development: ASPM & MCP1 Neurogenesis and migration NPC (neural progenitor cells) symmetric & asymmetric divisions ASPM & MCPH1 number of symmetric divisions DN Ad ama ge r e pair Orientation of division plane dyslexia 13

32 Brain growth & development: ASPM & MCP1 Neurogenesis and migration NPC (neural progenitor cells) symmetric & asymmetric divisions ASPM & MCPH1 number of symmetric divisions brain size microcephaly (abnormal variation) cranial volume (normal variation, sex-specific) area-specific cortical area (normal variation, sex-specific) dyslexia 13

33 So, how do genes influence language? In some sense, genes have a fundamental influence on language But this is not a simple matter a rewiring of the brain took place in some individual, call him Prometheus, yielding the operation of unbounded Merge, applying to concepts with intricate (and little understood) properties (Chomsky, 2010) How dodediu genes influence language? Dan 13

34 So, how do genes influence language? Genes do not directly do anything to language & speech DNA How dodediu genes influence language? Dan Language 13

35 So, how do genes influence language? Genes do not directly do anything to language & speech There are long, complex and bidirectional pathways linking the two DNA Gene networks How dodediu genes influence language? Dan Brains, vocal Cells & tissues tracts, ears Communities Language 13

36 So, how do genes influence language? Genes do not directly do anything to language & speech There are long, complex and bidirectional pathways linking the two Multiple timescales: milliseconds years DNA Gene networks How dodediu genes influence language? Dan Brains, vocal Cells & tissues tracts, ears Communities Language 13

37 So, how do genes influence language? Genes do not directly do anything to language & speech There are long, complex and bidirectional pathways linking the two Lots of genes of small effect, massive pleiotropy, and higher-order epistasis How dodediu genes influence language? Dan 13

38 So, how do genes influence language? Genes do not directly do anything to language & speech There are long, complex and bidirectional pathways linking the two Lots of genes of small effect, massive pleiotropy, and higher-order epistasis How dodediu genes influence language? Dan 13

39 So, how do genes influence language? Genes do not directly do anything to language & speech There are long, complex and bidirectional pathways linking the two Lots of genes of small effect, massive pleiotropy, and higher-order epistasis How dodediu genes influence language? Dan 13

40 So, how do genes influence language? Genes do not directly do anything to language & speech There are long, complex and bidirectional pathways linking the two Lots of genes of small effect, massive pleiotropy, and higher-order epistasis Gene environment interactions (epigenetics, developmental plasticity,...) (Transgenerational) phenotypic differences DNA methylation, etc. Parent of origin effects How dodediu genes influence language? Dan 14

41 Conclusions Just at the beginning Already some genes known complex, fascinating and non-intuitive mechanisms molecular windows into the genetic architecture Complex chain from genes. language and speech Environment is essential Most probably no language gene, no simplistic story Thanks to: Sarah Graham, Sonja Vernes, Simon Fisher Funding: Netherlands Organisation for Scientific Research ( Conclusions ) Vidi grant

42 Suggested reading General books: Jones, Steve (2000). The language of the genes. London: Flamingo. Ridley, M. (2004). Nature via nurture: genes, experience and what makes us human. London: Harper Perennial. Introductions to genetics: Snustad, D. P., & Simmons, M. J. (2010). Principles of genetics. John Wiley & Sons, Inc. Krebs, J. E., Kilpatrick, S. T., & Goldstein, E. S. (2013). Lewin s Genes XI. Jones and Bartlett Publishers, Inc. Suggested readings 14

43 Suggested reading Genetics of language: Graham, S. A., & Fisher, S. E. (2013). Decoding the genetics of speech and language. Current Opinion in Neurobiology 23: doi: /j.conb Kang, C., & Drayna, D. (2011). Genetics of speech and language disorders. Ann rev genomics hum genet 12: doi: /annurev-genom Smith, S. D., Grigorenko, E., Willcutt, E., Pennington, B. F., Olson, R. K., & DeFries, J. C. (2010). Etiologies and molecular mechanisms of communication disorders. Journal of developmental and behavioral pediatrics 31, doi: /dbp.0b013e3181ee3d9e Bishop, D. V. M. (2009). Genes, cognition, and communication: insights from neurodevelopmental disorders. Ann N Y Acad Sci 1156:1 18. doi: /j x Fisher, S. E. (2006). Tangled webs: tracing the connections between genes and cognition. Cognition 101: doi: /j.cognition Suggested readings 14