Advertisement

Genomic Imprinting and Human Psychology: Cognition, Behavior and Pathology

  • Lisa M. Goos
  • Gillian Ragsdale
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 626)

Abstract

Imprinted genes expressed in the brain are numerous and it has become clear that they play an important role in nervous system development and function. The significant influence of genomic imprinting during development sets the stage for structural and physiological variations affecting psychological function and behaviour, as well as other physiological systems mediating health and well-being. However, our understanding of the role of imprinted genes in behaviour lags far behind our understanding of their roles in perinatal growth and development. Knowledge of genomic imprinting remains limited among behavioral scientists and clinicians and research regarding the influence of imprinted genes on normal cognitive processes and the most common forms of neuropathology has been limited to date. In this chapter, we will explore how knowledge of genomic imprinting can be used to inform our study of normal human cognitive and behavioral processes as well as their disruption. Behavioural analyses of rare imprinted disorders, such as Prader-Willi and Angelman syndromes, provide insight regarding the phenotypic impact of imprinted genes in the brain, and can be used to guide the study of normal behaviour as well as more common but etiologically complex disorders such as ADHD and autism. Furthermore, hypotheses regarding the evolutionary development of imprinted genes can be used to derive predictions about their role in normal behavioural variation, such as that observed in food-related and social interactions.

Keywords

Autistic Spectrum Disorder Obsessive Compulsive Disorder Imprint Gene Turner Syndrome Angelman Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Keverne EB, Fundele R, Narasimha M et al. Genomic imprinting and the differential roles of parental genomes in brain development. Devel Brain Res 1996; 92:91–100.Google Scholar
  2. 2.
    Keverne EB. Genomic imprinting in the brain. Curr Op Neurobiol 1997; 7:463–468.PubMedGoogle Scholar
  3. 3.
    Pham NV, Nguyen MT, Hu JF et al. Dissociation of IGF2 and H19 imprinting in human brain. Brain Res 1998; 810(1–2):1–8.PubMedGoogle Scholar
  4. 4.
    Plagge A, Isles AR, Gordon E et al. Imprinted nesp55 influences behavioral reactivity to novel environments. Mol Cell Biol 2005; 25(8):3019–3026.PubMedGoogle Scholar
  5. 5.
    Polychronakos C, Kukuvitis A, Giannoukakis N et al. Parental imprinting effect at the INS-IGF2 diabetes susceptibility locus. Diabetologia 1995; 38(6):715–719.PubMedGoogle Scholar
  6. 6.
    Whittington J, Holland A, Webb T et al. Cognitive abilities and genotype in a population-based sample of people with Prader-Willi syndrome. J Intellect Disabil Res 2004; 48(Pt 2):172–187.PubMedGoogle Scholar
  7. 7.
    Flint J. Implications of genomic imprinting for psychiatric genetics. Psychol Med 1992; 22:5–10.PubMedGoogle Scholar
  8. 8.
    Davies W, Isles AR, Wilkinson LS. Imprinted genes and mental dysfunction. Ann Med 2001; 33(6):428–436.PubMedGoogle Scholar
  9. 9.
    Bassett SS, Avramopoulos D, Fallin D. Evidence for parent of origin effect in late-onset Alzheimer disease. Am J Med Genet 2002; 114(6):679–686.PubMedGoogle Scholar
  10. 10.
    Lamb JA, Barnby G, Bonora E et al. Analysis of IMGSAC autism susceptibility loci: evidence for sex limited and parent of origin specific effects. J Med Genet 2005; 42(2):132–137.PubMedGoogle Scholar
  11. 11.
    Ottman R, Annegers JF, Hauser WA et al. Higher risk of seizures in offspring of mothers than of fathers with epilepsy. Am J Hum Genet 1988; 43:257–264.PubMedGoogle Scholar
  12. 12.
    Isles AR, Wilkinson LS. Imprinted genes, cognition and behavior. Trends Cog Sci 2000; 4(8):309–318.Google Scholar
  13. 13.
    Barton SC, Ferguson-Smith AC, Fundele R et al. Influence of paternally imprinted genes on development. Development 1991; 113:679–688.PubMedGoogle Scholar
  14. 14.
    Keverne EB, Martel FL, Nevison CM. Primate brain evolution: genetic and functional considerations. Proc Roy Soc Lond, B 1996; 262:689–696.Google Scholar
  15. 15.
    Kandel ER, Schwartz JH, Jessell TM. Essentials of Neural Science and Behavior. Norwalk, Connecticut: Appleton and Lange, 1995.Google Scholar
  16. 16.
    Hole JW. Human Anatomy and Physiology. Dubuque, Iowa: Wm C Brown, 1984.Google Scholar
  17. 17.
    Ferris CF. Vasopressin/oxytocin and aggression. Novartis Found Symp 2005; 268:190–198.PubMedGoogle Scholar
  18. 18.
    Cushing BS, Kramer KM. Mechanisms underlying epigenetic effects of early social experience: the role of neuropeptides and steroids. Neurosci Biobehav Rev 2005; 29(7):1089–1105.PubMedGoogle Scholar
  19. 19.
    Fries AB, Ziegler TE, Kurian JR et al. Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. Proc Natl Acad Sci 2005; 102(47):17237–17240.PubMedGoogle Scholar
  20. 20.
    Allen ND, Logan K, Lally G et al. Distribution of parthenogenetic cells in the mouse brain and their influence on brain development and behavior. Proc Natl Acad Sci 1995; 92:10782–10786.PubMedGoogle Scholar
  21. 21.
    Keverne EB. Molecular genetic approaches to understanding brain development and behavior. Psychoneuroendocrinology 1994; 19:407–414.PubMedGoogle Scholar
  22. 22.
    Goos LM, Silverman I. The inheritance of cognitive skills. Does genomic imprinting play a role? J Neurogenet 2006; 20:19–40.PubMedGoogle Scholar
  23. 23.
    Flint J. The genetic basis of cognition. Brain Res Bull 1999; 122:2015–2031.Google Scholar
  24. 24.
    Plomin R, Hill L, Craig IW et al. A genome-wide scan of 1842 DNA markers for allelic associations with general cognitive ability: A five stage design using DNA pooling and extreme selected groups. Behav Genet 2001; 31(6):497–509.PubMedGoogle Scholar
  25. 25.
    Jensen AR. The puzzle of nongenetic variance. In: Sternberg RJ, Grigorenko EL, eds. Intelligence, Heredity and Environment. Cambridge: Cambridge University Press, 1998:42–88.Google Scholar
  26. 26.
    DeFries JC, Ashton GC, Johnson RC et al. Parent-offspring resemblance for specific cognitive abilities in two ethnic groups. Nature 1976; 261(5556):131–133.PubMedGoogle Scholar
  27. 27.
    DeFries JC, Johnson RC, Kuse AR et al. Familial resemblance for specific cognitive abilities. Behav Genet 1979; 9(1):23–43.PubMedGoogle Scholar
  28. 28.
    Loehlin JC, Sharan S, Jacoby R. In pursuit of the “spatial gene”: a family study. Behav Genet 1978; 8(1):27–41.PubMedGoogle Scholar
  29. 29.
    McGee MG. Intrafamilial correlations and heritability estimates for spatial ability in a Minnesota sample. Behav Genet 1978; 8(1):77–80.PubMedGoogle Scholar
  30. 30.
    Park J, Johnson RC, DeFries JC et al. Parent-offspring resemblance for specific cognitive abilities in Korea. Behav Genet 1978; 8(1):43–52.PubMedGoogle Scholar
  31. 31.
    Spuhler KP, Vandenberg SG. Comparison of parent-offspring resemblance for specific cognitive abilities. Behav Genet 1980; 10(4):413–418.PubMedGoogle Scholar
  32. 32.
    Spencer HG. The correlation between relatives on the supposition of genomic imprinting. Genetics 2002; 161:411–417.PubMedGoogle Scholar
  33. 33.
    Crow TJ. Introduction. In The Speciation of Modern Homo sapiens. Proc Br Acad 2002; 106:1–20.Google Scholar
  34. 34.
    Hughes C. Executive function in preschoolers: links with theory of mind and verbal ability. Brit J Dev Psychol 1998; 16:233–253.Google Scholar
  35. 35.
    Welsh M, Pennington B, Groisser D. A normative-developmental study of executive function. Devel Neuropsych 1991; 7:131–149.Google Scholar
  36. 36.
    Premack D, Woodruff G. Does the chimpanzee have a theory of mind? Behav Brain Sci 1978; 1:515–526.Google Scholar
  37. 37.
    Dunbar RIM. On the origin of the human mind. In: Caruthers P, Chamberlain A, eds. Evolution and the Human Mind: Modularity, Language and Meta-Cognition. Cambridge: Cambridge University Press, 2000:238–253.Google Scholar
  38. 38.
    Preston SD, de Waal FB. Empathy: Its ultimate and proximate bases. Behav Brain Sci 2002; 25(1):1–20.PubMedGoogle Scholar
  39. 39.
    Perry RJ, Rosen HR, Kramer JH et al. Hemispheric dominance for emotions, empathy and social behavior: evidence from right and left handers with frontotemporal dementia. Neurocase 2001; 7(2):145–160.PubMedGoogle Scholar
  40. 40.
    Shallice T. ‘Theory of mind’ and the prefrontal cortex. Brain 2001; 124(Pt 2):247–248.PubMedGoogle Scholar
  41. 41.
    Keysers C, Wicker B, Gazzola V et al. A touching sight: SII/PV activation during the observation and experience of touch. Neuron 2004; 42(2):335–346.PubMedGoogle Scholar
  42. 42.
    Dunbar RIM. The social brain hypothesis. Evol Anth 1998; 6:178–190.Google Scholar
  43. 43.
    Steffenburg S, Gillberg C, Hellgren L et al. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychi 1989; 30(3):405–416.Google Scholar
  44. 44.
    Auranen M, Vanhala R, Varilo T et al. A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25-27. Am J Hum Genet 2002; 71(4):777–790.PubMedGoogle Scholar
  45. 45.
    Buxbaum JD, Silverman JM, Smith CJ et al. Evidence for a susceptibility gene for autism on chromosome 2 and for genetic hetero geneity. Am J Hum Genet 2001; 68:1514–1520.PubMedGoogle Scholar
  46. 46.
    Collaborative Linkage Study of Autism (CLSA). An autosomal genomic screen for autism. Am J Med Genet (Neuropsychiatric Genetics) 1999; 88:609–615.Google Scholar
  47. 47.
    International Molecular Genetic Study of Autism Consortium (IMGSAC). A full genome screen for autism with evidence for linkage to a region on chromosome 7a. Hum Mol Genet 1998; 7:571–578.Google Scholar
  48. 48.
    International Molecular Genetic Study of Autism Consortium (IMGSAC). A genomewide screen for autism: strong evidence for linkage to chromosomes 2q, 7q and 16p. Am J Hum Genet 2001; 69:570–581.PubMedGoogle Scholar
  49. 49.
    Liu J, Nyholt DR, Magnussen P et al. A genomewide screen for autism susceptibility loci. Am J Hum Genet 2001; 69(2):327–340.PubMedGoogle Scholar
  50. 50.
    Philippe A, Martinez M, Guilloud-Bataille M et al. Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Hum Mol Genet 1999; 8(5):805–812.PubMedGoogle Scholar
  51. 51.
    Risch N, Spiker D, Lotspeich L et al. A genomic screen of autism: evidence for a multilocus etiology. Am J Hum Genet 1999; 65(2):493–507.PubMedGoogle Scholar
  52. 52.
    Yonan AL, Alarcon M, Cheng R et al. A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet 2003; 73(4):886–897.PubMedGoogle Scholar
  53. 53.
    Alarcon M, Yonan AL, Gilliam TC et al. Quantitative genome scan and Ordered-Subsets Analysis of autism endophenotypes support language QTLs. Mol Psychiatry, 2005.Google Scholar
  54. 54.
    Cantor RM, Kono N, Duvall JA et al. Replication of Autism Linkage: Fine-Mapping Peak at 17q21. Am J Hum Genet 2005; 76(6).Google Scholar
  55. 55.
    Vorstman JA, Staal WG, van Daalen E et al. Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism. Mol Psychiatry 2006; 11(1):1,18–28.Google Scholar
  56. 56.
    Badcock C, Crespi B. Imbalanced genomic imprinting in brain development: an evolutionary basis for the aetiology of autism. J Evol Biol 2006; 19(4):1007–1032.PubMedGoogle Scholar
  57. 57.
    Cook Jr EH, Lindgren V, Leventhal BL et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 1997; 60(4):928–934.PubMedGoogle Scholar
  58. 58.
    Schroer RJ, Phelan MC, Michaelis RC et al. Autism and maternally derived aberrations of chromosome 15q. Am J Med Genet 1998; 76(4):327–336.PubMedGoogle Scholar
  59. 59.
    Repetto GM, White LM, Bader PJ et al. Interstitial duplications of chromosome region 15q11q13: clinical and molecular characterization. Am J Med Genet 1998; 79(2):82–89.PubMedGoogle Scholar
  60. 60.
    Nurmi EL, Dowd M, Tadevosyan-Leyfer O et al. Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13. J Am Acad Child Adolesc Psychiatry 2003; 42(7):856–863.PubMedGoogle Scholar
  61. 61.
    Bittel DC, Kibiryeva N, Talebizadeh Z et al. Microarray analysis of gene/transcript expression in Angelman syndrome: deletion versus UPD. Genomics 2005; 85(1):85–91.PubMedGoogle Scholar
  62. 62.
    Ashley-Koch A, Wolpert CM, Menold MM et al. Genetic studies of autistic disorder and chromosome 7. Genomics 1999; 61(3):227–236.PubMedGoogle Scholar
  63. 63.
    Donnelly SL, Wolpert CM, Menold MM et al. Female with autistic disorder and monosomy X (Turner syndrome): parent-of-origin effect of the X chromosome. Am J Med Genet 2000; 96(3):312–316.PubMedGoogle Scholar
  64. 64.
    Ronald A, Happe F, Plomin R. The genetic relationship between individual differences in social and nonsocial behaviors characteristic of autism. Dev Sci 2005; 8(5):444–458.PubMedGoogle Scholar
  65. 65.
    Ronald A, Happe F, Bolton P et al. Genetic heterogeneity between the three components of the autism spectrum: a twin study. J Am Child Adolesc Psychiatry 2006; 45(6):691–699.Google Scholar
  66. 66.
    Creswell CS, Skuse DH. Autism in association with Turner syndrome: genetic implications for male vulnerability to passive developmental disorders. Neurocase 1999; 5:101–108.Google Scholar
  67. 67.
    Good CD, Lawrence K, Thomas NS et al. Dosage-sensitive X-linked locus influences the development of amygdala and orbitofrontal cortex and fear recognition in humans. Brain 126(Pt 11):2431–2446.Google Scholar
  68. 68.
    Elgar K, Campbell R, Skuse D. Are you looking at me? Accuracy in processing line-of-sight in Turner syndrome. Proc R Soc Lond B Biol Sci 2002; 269(1508):2415–2422.Google Scholar
  69. 69.
    Wicker B, Perrett DI, Baron-Cohen S et al. Being the target of another’s emotion: a PET study. Neuropsychologia 2003; 41(2):139–146.PubMedGoogle Scholar
  70. 70.
    Kesler SR, Blasey CM, Brown WE et al. Effects of X-monosomy and X-linked imprinting on superior temporal gyrus morphology in Turner syndrome. Biol Psychiatry 2003; 54(6):636–646.PubMedGoogle Scholar
  71. 71.
    Baron-Cohen S. Mindblindness: An essay on autism and theory of mind. Cambridge, Mass: MIT Press/Bradford Books, 1995.Google Scholar
  72. 72.
    Skuse DH, James RS, Bishop DV et al. Evidence from Turner’s syndrome of an imprinted X-linked locus affecting cognitive function. Nature 1997; 387(6634):705–708.PubMedGoogle Scholar
  73. 73.
    Skuse DH. Imprinting, the X-chromosome and the male brain: explaining sex differences in the liability to autism. Pediatr Res 2000; 47(1):9–16.PubMedGoogle Scholar
  74. 74.
    Zechner U, Wilda M, Kehrer-Sawatzki H et al. A high density of X-linked genes for general cognitive ability: a run-away process shaping human evolution? Trends Genet 2001; 17(12):697–701.PubMedGoogle Scholar
  75. 75.
    Raefski AS, O’Neill MJ. Identification of a cluster of X-linked imprinted genes in mice. Nat Genet 2005; 37(6):620–624.PubMedGoogle Scholar
  76. 76.
    Davies W, Isles A, Smith R et al. Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice. Nat Genet 2005; 37(6):625–629.PubMedGoogle Scholar
  77. 77.
    Haig D, Westoby M. Parent specific gene expression and the triploid endosperm. Am Nat 1989; 134:147–155.Google Scholar
  78. 78.
    Haig D. Genomic Imprinting and Kinship. New Brunswick, NJ: Rutgers University Press, 2002.Google Scholar
  79. 79.
    Canteras NS, Chiavegatto S, Valle LE et al. Severe reduction of rat defensive behavior to a predator by discrete hypothalamic chemical lesions. Brain Res Bull 1997; 44(3):297–305.PubMedGoogle Scholar
  80. 80.
    Risold PY, Thompson RH, Swanson LW. The structural organization of connections between hypothalamus and cerebral cortex. Brain Res Rev 1997; 24:197–254.PubMedGoogle Scholar
  81. 81.
    Smuts B. Social relationships and life history of primates. In: Galloway A, Zihlman AL eds. The Evolving Female: A Life-History Perspective. Princeton, NJ: Princeton University Press, 1997:60–68.Google Scholar
  82. 82.
    Cheney D, Seyfarth R, Smuts B. Social relationships and social cognition in nonhuman primates. Science 1986; 234(4782):1361–1366.PubMedGoogle Scholar
  83. 83.
    Shallice T. Specific impairments of planning. Philos Trans R Soc Lond B Biol Sci 1982; 298(1089): 199–209.PubMedGoogle Scholar
  84. 84.
    Dunbar RIM. Neocortex size as a constraint on group size in primates. J Hum Evol 1992; 20:469–493.Google Scholar
  85. 85.
    Joffe TH, Dunbar RI. Visual and socio-cognitive information processing in primate brain evolution. Proc Biol Sci 1997; 264(1386):1303–1307.PubMedGoogle Scholar
  86. 86.
    Seyfarth RM, Cheney DL. What are big brains for? Proc Natl Acad Sci 2002; 99(7):4141–4142.PubMedGoogle Scholar
  87. 87.
    Lefebvre L, Viville S, Barton SC et al. Abnormal maternal behavior and growth retardation associated with loss of the imprinted gene Mest. Nat Genet 1998; 20:163–169.PubMedGoogle Scholar
  88. 88.
    Welch MG, Ruggiero DA. Predicted role of secretin and oxytocin in the treatment of behavioral and developmental disorders: implications for autism. Int Rev Neurobiol 2005; 71:273–315.PubMedGoogle Scholar
  89. 89.
    Wu S, Jia M, Ruan Y et al. Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry 2005; 58(1):74–77.PubMedGoogle Scholar
  90. 90.
    Green L, Fein D, Modahl C et al. Oxytocin and autistic disorder: alterations in peptide forms. Biol Psychiatry 2001; 50(8):609–613.PubMedGoogle Scholar
  91. 91.
    Insel TR, O’Brien DJ, Leckman JF. Oxytocin, vasopressin and autism: is there a connection? Biol Psychiatry 1999; 45(2):145–157.PubMedGoogle Scholar
  92. 92.
    Kennedy DP, Redcay E, Courchesne E. Failing to deactivate: resting functional abnormalities in autism. Proc Natl Acad Sci 2006; 103(21):8275–8280.PubMedGoogle Scholar
  93. 93.
    Belmonte MK, Carper RA. Monozygotic twins with Asperger syndrome: differences in behavior reflect variations in brain structure and function. Brain Cogn 2006; 61(1):110–121.PubMedGoogle Scholar
  94. 94.
    Chandana SR, Behen ME, Juhasz C et al. Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism. Int J Dev Neurosci 2005; 23(2–3):171–182PubMedGoogle Scholar
  95. 95.
    Baron-Cohen S. The essential difference: men, women and the extreme male brain. London: Allen Lane Penguin Books, 2003.Google Scholar
  96. 96.
    Mental Illness. What does it mean? In: Great Britain Department of Health Great Britain Department of Health Social Services Inspectorate, ed. Health of the Nation. London, UK: HMSO, 1991.Google Scholar
  97. 97.
    Baron-Cohen S. Two new theories of autism: hyper-systemising and assortative mating. Arch Dis Child 2006; 91(1):2–5.PubMedGoogle Scholar
  98. 98.
    Finkel D, McGue M. Sex differences and non-additivity in heritability of the Multidimensional Personality Questionnaire Scales. J Pers Soc Psychol 1997; 72(4):929–938.PubMedGoogle Scholar
  99. 99.
    Cassidy SB, Morris CA. Behavioral phenotypes in genetic syndromes: genetic clues to human behavior. Adv Pediatr 2002; 49:59–86.PubMedGoogle Scholar
  100. 100.
    Skuse DH. Behavioral phenotypes: what do they teach us? Arch Dis Child 2000; 82(3):222–225.PubMedGoogle Scholar
  101. 101.
    Butler M. Prader-Willi Syndrome: Current understanding of cause and diagnosis. Am J Med Genet 1990; 35:319–332.PubMedGoogle Scholar
  102. 102.
    Moore T, Haig D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet 1991; 7(2):45–49.PubMedGoogle Scholar
  103. 103.
    Friend WC. Psychopathology and nonmendelian inheritance. In: M.V. Seeman, ed(s). Gender and Psychopathology. Washington, DC: American Psychiatric Press, 1995:41–61.Google Scholar
  104. 104.
    Rankinen T, Zuberi A, Chagnon YC et al. The human obesity gene map: the 2005 update. Obesity (Silver Springs) 2006; 14(4):529–644.Google Scholar
  105. 105.
    Dong C, Li WD, Geller F et al. Possible genomic imprinting of three human obesity-related genetic loci. Am J Hum Genet 2005; 76(3):427–437.PubMedGoogle Scholar
  106. 106.
    Lindsay RS, Kobes S, Knowler WC et al. Genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of type 2 diabetes and BMI in Pima Indians. Diabetes 2001; 50(12):2850–2857.PubMedGoogle Scholar
  107. 107.
    Parkinson WL, Weingarten HP. Dissociative analysis of ventromedial hypothalamic obesity syndrome. Am J Physiol 1990; 259(4 Pt 2):R829–835.PubMedGoogle Scholar
  108. 108.
    Tecott LH, Sun LM, Akana SF et al. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 1995; 374(6522):542–546.PubMedGoogle Scholar
  109. 109.
    Halford JC, Blundell JE. Separate systems for serotonin and leptin in appetite control. Ann Med 2000; 32(3):222–232.PubMedGoogle Scholar
  110. 110.
    Haig D, Wharton R. Prader-Willi syndrome and the evolution of human childhood. Am J Hum Biol 2003; 15(3):320–329.PubMedGoogle Scholar
  111. 111.
    Bruning JC, Gautam D, Burks DJ et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000; 289(5487):2122–2125.PubMedGoogle Scholar
  112. 112.
    Bennett ST, Wilson AJ, Esposito L et al. Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group. Nat Genet 1997; 17(3):350–352.PubMedGoogle Scholar
  113. 113.
    Le Stunff C, Fallin D, Bougneres P. Paternal transmission of the very common class I INS VNTR alleles predisposes to childhood obesity. Nat Genet 2001; 29(1):96–99.PubMedGoogle Scholar
  114. 114.
    Ong KK, Petry CJ, Barratt BJ et al. Maternal-fetal interactions and birth order influence insulin variable number of tandem repeats allele class associations with head size at birth and childhood weight gain. Diabetes 2004; 53(4):1128–1133.PubMedGoogle Scholar
  115. 115.
    Morison IM, Reeve AE. A catalogue of imprinted genes and parent-of-origin effects in humans and animals. Hum Mol Genet 1998; 7(10):1599–1609.PubMedGoogle Scholar
  116. 116.
    Moore GE, Abu-Amero SN, Bell G et al. Evidence that insulin is imprinted in the human yolk sac. Diabetes 2001; 50(1):199–203.PubMedGoogle Scholar
  117. 117.
    Giddings SJ, King CD, Harman KW et al. Allele specific inactivation of insulin 1 and 2, in the mouse yolk sac, indicates imprinting. Nat Genet 1994; 6(3):310–313.PubMedGoogle Scholar
  118. 118.
    DeChiara TM, Robertson EJ, Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 1991; 64(4):849–859.PubMedGoogle Scholar
  119. 119.
    Barlow DP, Stoger R, Herrmann BG et al. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 1991; 349(6304):84–87.PubMedGoogle Scholar
  120. 120.
    Bartolomei MS, Zemel S, Tilghman SM. Parental imprinting of the mouse H19 gene. Nature 1991; 351(6322):153–155.PubMedGoogle Scholar
  121. 121.
    Bachner-Melman R, Zohar AH, Nemanov L et al. Association between the insulin-like growth factor 2 gene (IGF2) and scores on the Eating Attitudes Test in nonclinical subjects: a family-based study. Am J Psychiatry 2005; 162(12):2256–2262.PubMedGoogle Scholar
  122. 122.
    Cripps RL, Martin-Gronert MS, Ozanne SE. Fetal and perinatal programming of appetite. Clin Sci (Lond) 2005; 109(1):1–11.Google Scholar
  123. 123.
    Isse N, Ogawa Y, Tamura N et al. Structural organization and chromosomal assignment of the human obese gene. J Biol Chem 1995; 270(46):27728–27733.PubMedGoogle Scholar
  124. 124.
    Waterland RA. Do maternal methyl supplements in mice affect DNA methylation of offspring? J Nutr 2003; 133(1):238; author reply 239.PubMedGoogle Scholar
  125. 125.
    Waterland RA, Lin JR, Smith CA et al. Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum Mol Genet 2006; 15(5):705–716.PubMedGoogle Scholar
  126. 126.
    Gardner DK, Lane M. Ex vivo early embryo development and effects on gene expression and imprinting. Reprod Fertil Dev 2005; 17(3):361–370.PubMedGoogle Scholar
  127. 127.
    Ravelli AC, van Der Meulen JH, Osmond C et al. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 1999; 70(5):811–816.PubMedGoogle Scholar
  128. 128.
    Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992; 35(7):595–601.PubMedGoogle Scholar
  129. 129.
    Junien C, Gallou-Kabani C, Vige A et al. Nutritionnal epigenomics: consequences of unbalanced diets on epigenetics processes of programming during lifespan and between generations. Ann Endocrinol (Paris) 2005; 66(2 Pt 3):2S19–2S28.Google Scholar
  130. 130.
    Karno M, Golding JM, Sorenson SB et al. The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry 1988; 45(12):1094–1099.PubMedGoogle Scholar
  131. 131.
    Alsobrook 2nd JP, Zohar AH, Leboyer M et al. Association between the COMT locus and obsessive-compulsive disorder in females but not males. Am J Med Genet 2002; 114(1):116–120.PubMedGoogle Scholar
  132. 132.
    State MW, Dykens EM, Rosner B et al. Obsessive-compulsive symptoms in Prader-Willi and “Prader-Willi-Like” patients. J Am Acad Child Adolesc Psychiatry 1999; 38(3):329–334.PubMedGoogle Scholar
  133. 133.
    Martin A, State M Anderson GM et al. Cerebrospinal fluid levels of oxytocin in Prader-Willi syndrome: a preliminary report. Biol Psychiatry 1998; 44(12):1349–1352.PubMedGoogle Scholar
  134. 134.
    Leckman JF, Goodman WK, North WG et al. Elevated cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder. Comparison with Tourette’s syndrome and healthy controls. Arch Gen Psychiatry 1994; 51(10):782–792.PubMedGoogle Scholar
  135. 135.
    Walitza S, Wewetzer C, Warnke A et al. 5-HT2A promoter polymorphism-1438G/A in children and adolescents with obsessive-compulsive disorders. Mol Psychiatry 2002; 7(10):1054–1057.PubMedGoogle Scholar
  136. 136.
    Ozaki N, Goldman D, Kaye WH et al. Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry 2003; 8(11):895, 933–6.Google Scholar
  137. 137.
    Joel D. Current animal models of obsessive compulsive disorder: A critical review. Prog Neuropsychopharmacol Biol Psychiatry, 2006.Google Scholar
  138. 138.
    Cavaillé J, Buiting K, Kiefmann M et al. Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc Natl Acad Sci 2000; 97(26): 14311–14316.PubMedGoogle Scholar
  139. 139.
    Filipowicz W. Imprinted expression of small nucleolar RNAs in brain: Time for RNomics. Proc Natl Acad Sci 2000; 97(26):14035–14037.PubMedGoogle Scholar
  140. 140.
    de los Santos T, Schweizer J, Rees CA et al. Small evolutionarily conserved RNA, resembling C/D box small nucleolar RNA, is transcribed from pwcrl, a novel imprinted gene in the Prader-Willi deletion region, which Is highly expressed in brain. Am J Hum Genet 2000; 67(5):1067–1082.PubMedGoogle Scholar
  141. 141.
    Swanson JM, Sergeant JA, Taylor E et al. Attention-deficit hyperactivity disorder and hyperkinetic disorder. Lancet 1998; 351(9100):429–433.PubMedGoogle Scholar
  142. 142.
    APA. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Association, 1994.Google Scholar
  143. 143.
    Leo D, Sorrentino E, Volpicelli F et al. Altered midbrain dopaminergic neurotransmission during development in an animal model of ADHD. Neurosci Biobehav Rev 2003; 27(7):661–669.PubMedGoogle Scholar
  144. 144.
    Burke JD, Loeber R, Lahey BB et al. Developmental transitions among affective and behavioral disorders in adolescent boys. J Child Psychol Psychiatry 2005; 46(11):1200–1210.PubMedGoogle Scholar
  145. 145.
    Volk HE, Neuman RJ, Todd RD. A systematic evaluation of ADHD and comorbid psychopathology in a population-based twin sample. J Am Acad Child Adolesc Psychiatry 2005; 44(8):768–775.PubMedGoogle Scholar
  146. 146.
    Dick DM, Viken RJ, Kaprio J et al. Understanding the covariation among childhood externalizing symptoms: genetic and environmental influences on conduct disorder, attention deficit hyperactivity disorder and oppositional defiant disorder symptoms. J Abnorm Child Psychol 2005; 33(2):219–229.PubMedGoogle Scholar
  147. 147.
    Willcutt EG, Pennington BF, Chhabildas NA et al. Psychiatric comorbidity associated with DSM-IV ADHD in a nonreferred sample of twins. J Am Acad Child Adolesc Psychiatry 1999; 38(11): 1355–1362.PubMedGoogle Scholar
  148. 148.
    Thapar A, Harrington R, McGuffin P. Examining the comorbidity of ADHD-related behaviors and conduct problems using a twin study design. Br J Psychiatry 2001; 179:224–229.PubMedGoogle Scholar
  149. 149.
    Faraone SV, Biederman J. Do attention deficit hyperactivity disorder and major depression share familial risk factors? J Nerv Ment Dis 1997; 185(9):533–541.PubMedGoogle Scholar
  150. 150.
    Tsai SJ, Cheng CY, Yu YW et al. Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology and antidepressant response. Am J Med Genet B Neuropsychiatr Genet 2003; 123(1):19–22.Google Scholar
  151. 151.
    Blackman GL, Ostrander R, Herman KC. Children with ADHD and depression: a multisource, multimethod assessment of clinical, social and academic functioning. J Atten Disord 2005; 8(4):195–207.PubMedGoogle Scholar
  152. 152.
    LeBlanc N, Morin D. Depressive symptoms and associated factors in children with attention deficit hyperactivity disorder. J Child Adol Psychiatric Nurs 2004; 17(2):49–55.Google Scholar
  153. 153.
    Mick E, Biederman J, Santangelo S et al. The influence of gender in the familial association between ADHD and major depression. J Nerv Ment Dis 2003; 191(11):699–705.PubMedGoogle Scholar
  154. 154.
    Faraone SV, Biederman J, Mennin D et al. Attention-deficit hyperactivity disorder with bipolar disorder: a familial subtype? J Am Acad Child Adolesc Psychiatry 1997; 36(10):1378–1387.PubMedGoogle Scholar
  155. 155.
    Biederman J, Faraone SV, Keenan K et al. Evidence of familial association between attention deficit disorder and major affective disorders. Arch Gen Psychiatry 1991; 48(7):633–642.PubMedGoogle Scholar
  156. 156.
    Faraone SV, Biederman J, Mennin D et al. Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness. Am J Med Genet 1998; 81(1):108–116.PubMedGoogle Scholar
  157. 157.
    Banaschewski T, Brandeis D, Heinrich H et al. Association of ADHD and conduct disorder—brain electrical evidence for the existence of a distinct subtype. J Child Psychol Psychiatry 2003; 44(3): 356–376.PubMedGoogle Scholar
  158. 158.
    Doyle AE, Faraone SV. Familial links between attention deficit hyperactivity disorder, conduct disorder and bipolar disorder. Curr Psychiatry Rep 2002; 4(2):146–152.PubMedGoogle Scholar
  159. 159.
    Smalley SL, McGough JJ, Del’Homme M et al. Familial clustering of symptoms and disruptive behaviors in multiplex families with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2000; 39(9):1135–1143.PubMedGoogle Scholar
  160. 160.
    Faraone SV, Biederman J, Monuteaux MC. Attention-deficit disorder and conduct disorder in girls: evidence for a familial subtype. Biol Psychiatry 2000; 48(1):21–29.PubMedGoogle Scholar
  161. 161.
    Wigren M, Hansen S. ADHD symptoms and insistence on sameness in Prader-Willi syndrome. J Intellect Disabil Res 2005; 49 (Pt 6):449–456.PubMedGoogle Scholar
  162. 162.
    Couper R. Prader-Willi syndrome. J Paediatr Child Health 1999; 35(4):331–334.PubMedGoogle Scholar
  163. 163.
    Watanabe H, Ohmori O, Abe K. Recurrent brief depression in Prader-Willi syndrome: a case report. Psychiatr Genet 1997; 7(1):41–44.PubMedGoogle Scholar
  164. 164.
    Dykens EM, Cassidy SB. Correlates of maladaptive behavior in children and adults with Prader-Willi syndrome. Am J Med Genet 1995; 60(6):546–549.PubMedGoogle Scholar
  165. 165.
    Swaab DF. Neuropeptides in hypothalamic neuronal disorders. Int Rev Cytol 2004; 240:305–375.PubMedGoogle Scholar
  166. 166.
    Mao R, Jalal SM, Snow K et al. Characteristics of two cases with dup(15)(q11.2-q12): one of maternal and one of paternal origin. Genet Med 2000; 2(2):131–135.PubMedGoogle Scholar
  167. 167.
    Cattanach BM, Kirk M. Differential activity of maternally and paternally derived chromosome regions in mice. Nature 1985; 315(6019):496–498.PubMedGoogle Scholar
  168. 168.
    Lichter DG, Jackson LA, Schachter M. Clinical evidence of genomic imprinting in Tourette’s Syndrome. Neurology 1995; 45:924–928.PubMedGoogle Scholar
  169. 169.
    McMahon FJ, Stine OC, Meyers DA et al. Patterns of maternal transmission in bipolar affective disorder. Am J Hum Genet 1995; 56:1277–1286.PubMedGoogle Scholar
  170. 170.
    Borglum AD, Kirov G, Craddock N et al. Possible parent-of-origin effect of Dopa decarboxylase in susceptibility to bipolar affective disorder. Am J Med Genet, B: Neuropsychiatr Genet 2003; 117(1):18–22.Google Scholar
  171. 171.
    Hawi Z, Dring M, Kirley A et al. Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample. Mol Psychiatry 2002; 7(7):718–725.PubMedGoogle Scholar
  172. 172.
    Sheehan K, Lowe N, Kirley A et al. Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Mol Psychiatry 2005; 10(10):944–949.PubMedGoogle Scholar
  173. 173.
    Curran S, Purcell S, Craig I et al. The serotonin transporter gene as a QTL for ADHD. Am J Med Genet B Neuropsychiatr Genet 2005; 134(1):42–47.Google Scholar
  174. 174.
    Stoltenberg SF, Glass JM, Chermack ST et al. Possible association between response inhibition and a variant in the brain-expressed tryptophan hydroxylase-2 gene. Psychiatr Genet 2006; 16(1):35–38.PubMedGoogle Scholar
  175. 175.
    Zill P, Baghai TC, Zwanzger P et al. SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression. Mol Psychiatry 2004; 9(11):1030–1036.PubMedGoogle Scholar
  176. 176.
    Zill P, Buttner A, Eisenmenger W et al. Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene in suicide victims. Biol Psychiatry 2004; 56(8):581–586.PubMedGoogle Scholar
  177. 177.
    Koponen E, Rantamaki T, Voikar V et al. Enhanced BDNF signaling is associated with an antidepressant-like behavioral response and changes in brain monoamines. Cell Mol Neurobiol 2005; 25(6):973–980.PubMedGoogle Scholar
  178. 178.
    Mattson MP, Maudsley S, Martin B. BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 2004; 27(10):589–594.PubMedGoogle Scholar
  179. 179.
    Kent L, Green E, Hawi Z et al. Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD. Mol Psychiatry 2005; 10(10):939–943.PubMedGoogle Scholar
  180. 180.
    Goos LM, Ezzatian P, Schachar R. Parent-of-origin effects in Attention Deficit Hyperactivity Disorder (ADHD). Psychiatry Res in press.Google Scholar
  181. 181.
    Marmorstein NR, Iacono WG. Major depression and conduct disorder in youth: associations with parental psychopathology and parent-child conflict. J Child Psychol Psychiatry 2004; 45(2):377–386.PubMedGoogle Scholar
  182. 182.
    Marmorstein NR, Malone SM, Iacono WG. Psychiatric disorders among offspring of depressed mothers: associations with paternal psychopathology. Am J Psychiatry 2004; 161(9):1588–1594.PubMedGoogle Scholar
  183. 183.
    Hicks BM, Krueger RF, Iacono WG et al. Family transmission and heritability of externalizing disorders: a twin-family study. Arch Gen Psychiatry 2004; 61(9):922–928.PubMedGoogle Scholar
  184. 184.
    Pfiffner LJ, McBurnett K, Rathouz PJ et al. Family correlates of oppositional and conduct disorders in children with attention deficit/hyperactivity disorder. J Abnorm Child Psychol 2005; 33(5):551–563.PubMedGoogle Scholar
  185. 185.
    Haber JR, Jacob T, Heath AC. Paternal alcoholism and offspring conduct disorder: evidence for the ‘common genes’ hypothesis. Twin Res Hum Genet 2005; 8(2):120–131.PubMedGoogle Scholar
  186. 186.
    Comings DE, Gade-Andavolu R, Gonzalez N et al. Comparison of the role of dopamine, serotonin and noradrenaline genes in ADHD, ODD and conduct disorder: multivariate regression analysis of 20 genes. Clin Genet 2000; 57(3):178–196.PubMedGoogle Scholar
  187. 187.
    Castellanos FX, Tannock R. Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 2002; 3(8):617–628.PubMedGoogle Scholar
  188. 188.
    Crosbie J, Schachar R. Deficient inhibition as a marker for familial ADHD. Am J Psychiatry 2001; 158:1884–1890.PubMedGoogle Scholar
  189. 189.
    Schachar R, Mota VL, Logan GD et al. Confirmation of an inhibitory control deficit in attention-deficit/ hyperactivity disorder. J Abnorm Child Psychol 2000; 28(3):227–235.PubMedGoogle Scholar
  190. 190.
    Kruglyak L, Lander ES. High-resolution genetic mapping of complex traits. Am J Hum Genet 1995; 56(5):1212–1223.PubMedGoogle Scholar
  191. 191.
    Gershon ES, Badner JA, Detera-Wadleigh SD et al. Maternal inheritance and chromosome 18 allele sharing in unilineal bipolar illness pedigrees. Am J Med Genet 1996; 67(2):202–207.PubMedGoogle Scholar
  192. 192.
    Biederman J, Newcorn J, Sprich S. Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety and other disorders. Am J Psychiatry 1991; 148(5):564–577.PubMedGoogle Scholar
  193. 193.
    Faraone SV, Biederman J, Keenan K et al. A family-genetic study of girls with DSM-III attention deficit disorder. Am J Psychiatr 1991; 148(1):112–117.PubMedGoogle Scholar
  194. 194.
    Schmitz M, Cadore L, Paczko M et al. Neuropsychological performance in DSM-IV ADHD subtypes: an exploratory study with untreated adolescents. Can J Psychiatr 2002; 47(9):863–869.Google Scholar
  195. 195.
    Murphy KR, Barkley RA, Bush T. Young adults with attention deficit hyperactivity disorder: subtype differences in comorbidity, educational and clinical history. J Nerv Ment Dis 2002; 190(3):147–157.PubMedGoogle Scholar
  196. 196.
    Chhabildas N, Pennington BF, Willcutt EG. A comparison of the neuropsychological profiles of the DSM-IV subtypes of ADHD. J Abn Child Psychol 2001; 29(6):529–540.Google Scholar
  197. 197.
    Faraone SV, Biederman J, Mick E et al. A family study of psychiatric comorbidity in girls and boys with attention-deficit/hyperactivity disorder. Biol Psychiatry 2001; 50(8):586–592.PubMedGoogle Scholar
  198. 198.
    Biederman J, Mick E, Faraone SV et al. Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric clinic. Am J Psychiatr 2002; 159(1):36–42.PubMedGoogle Scholar
  199. 199.
    Graetz BW, Sawyer MG, Baghurst P. Gender differences among children with DSM-IV ADHD in Australia. J Am Acad Child Adolesc Psychiatry 2005; 44(2):159–168.PubMedGoogle Scholar
  200. 200.
    Dykens EM, Hodapp RM. Research in mental retardation: toward an etiologic approach. J Child Psychol Psychiatry 2001; 42(1):49–71.PubMedGoogle Scholar
  201. 201.
    Abdolmaleky HM, Thiagalingam S, Wilcox M. Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements, applications and future scope. Am J Pharmacogenomics 2005; 5(3):149–160.PubMedGoogle Scholar
  202. 202.
    Koenig K, Klin A, Schultz R. Deficits in social attribution ability in Prader—Willi Syndrome. J Autism Dev Disord 2004; 34(5).Google Scholar
  203. 203.
    Dick DM, Edenberg HJ, Xuei X et al. Association of GABRG3 with alcohol dependence. Alcohol Clin Exp Res 2004; 28(1):4–9.PubMedGoogle Scholar
  204. 204.
    Cookson WO, Moffatt MF. Genetics of asthma and allergic disease. Hum Mol Genet 2000; 9(16): 2359–2364.PubMedGoogle Scholar
  205. 205.
    Cookson WO, Young RP, Sandford AJ et al. Maternal inheritance of atopic IgE responsiveness on chromosome 11q. Lancet 1992; 340(8816):381–384.PubMedGoogle Scholar
  206. 206.
    McCann JA, Xu YQ, Frechette R et al. The insulin-like growth factor-II receptor gene is associated with type 1 diabetes: evidence of a maternal effect. J Clin Endocrinol Metab 2004; 89(11):5700–5706.PubMedGoogle Scholar
  207. 207.
    Polychronakos C, Kukuvitis A. Parental genomic imprinting in endocrinopathies. Eur J Endocrinol 2002; 147(5):561–569.PubMedGoogle Scholar
  208. 208.
    Li Q, Athan ES, Wei M et al. TP73 allelic expression in human brain and allele frequencies in Alzheimer’s disease. BMC Med Genet 2004; 5:14.PubMedGoogle Scholar
  209. 209.
    Steen E, Terry BM, Rivera EJ et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—is this type 3 diabetes? J Alzheimers Dis 2005; 7(1):63–80.PubMedGoogle Scholar
  210. 210.
    de la Monte SM, Wands JR. Review of insulin and insulin-like growth factor expression, signaling and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimers Dis 2005; 7(1):45–61.PubMedGoogle Scholar
  211. 211.
    Huxtable SJ, Saker PJ, Haddad L et al. Analysis of parent-offspring trios provides evidence for linkage and association between the insulin gene and type 2 diabetes mediated exclusively through paternally transmitted class III variable number tandem repeat alleles. Diabetes 2000; 49(1):126–130.PubMedGoogle Scholar
  212. 212.
    Sakatani T, Wei M, Katoh M et al. Epigenetic heterogeneity at imprinted loci in normal populations. Biochem Biophys Res Commun 2001; 283(5):1124–1130.PubMedGoogle Scholar
  213. 213.
    Chen M, Gavrilova O, Liu J et al. Alternative Gnas gene products have opposite effects on glucose and lipid metabolism. Proc Natl Acad Sci 2005; 102(20):7386–7391.PubMedGoogle Scholar
  214. 214.
    Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab 2004; 89(6): 2526–2539.PubMedGoogle Scholar
  215. 215.
    Rodriguez S, Gaunt TR, O’Dell SD et al. Haplotypic analyses of the IGF2-INS-TH gene cluster in relation to cardiovascular risk traits. Hum Mol Genet 2004; 13(7):715–725.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  1. 1.Department of Psychiatry Research The Hospital for Sick ChildrenThe University of TorontoTorontoCanada
  2. 2.Leverhulme Centre for Human Evolutionary StudiesCambridgeUK

Personalised recommendations