二十世纪的遗传学很难解释神经精神疾病的不规则行为。自闭症和精神分裂症无视自然选择的原则;它们具有高度遗传性,但生殖成功率较低。然而,他们坚持。这种条件的遗传起源被变量表达的问题所混淆,也就是说,当给定的遗传畸变可以导致几种不同疾病中的任何一种。此外,自闭症和精神分裂症发生在一系列严重程度上,从轻度和亚临床病例到公开和致残。这种不规则性反映了遗传性缺失的问题;尽管数百个基因可能与自闭症或精神分裂症有关,他们总共只占一小部分。更高分辨率的技术,全基因组分析已经开始阐明人类基因组的不规则和不可预测的行为。因此,特别是神经精神疾病和一般复杂疾病的起源已经被阐明。人类基因组的特征是高度的结构和行为变异性:DNA含量变异,上位性,基因表达的随机性,和表观遗传变化。随着进化缩放系统发育树,这些元素变得更加复杂。它们与大脑发育和功能特别相关。基因组变异是复杂疾病起源的窗口,神经精神疾病,特别是神经发育障碍。基因组变异性,碰巧的是,也是进化的燃料。在自闭症和精神分裂症患者中,主持灵长类动物和人类谱系进化的基因组事件过多。以及智力残疾和癫痫。推动进化的人类基因组的特殊品质可能,在某种程度上,有助于神经精神疾病是一个不小的兴趣。
Twentieth-century genetics was hard put to explain the irregular behavior of neuropsychiatric disorders. Autism and schizophrenia defy a principle of natural selection; they are highly heritable but associated with low reproductive success. Nevertheless, they persist. The genetic origins of such conditions are confounded by the problem of variable expression, that is, when a given genetic aberration can lead to any one of several distinct disorders. Also, autism and schizophrenia occur on a spectrum of severity, from mild and subclinical cases to the overt and disabling. Such irregularities reflect the problem of missing heritability; although hundreds of genes may be associated with autism or schizophrenia, together they account for only a small proportion of cases. Techniques for higher resolution, genomewide analysis have begun to illuminate the irregular and unpredictable behavior of the human genome. Thus, the origins of neuropsychiatric disorders in particular and complex disease in general have been illuminated. The human genome is characterized by a high degree of structural and behavioral variability: DNA content variation, epistasis, stochasticity in gene expression, and epigenetic changes. These elements have grown more complex as evolution scaled the phylogenetic tree. They are especially pertinent to brain development and function. Genomic variability is a window on the origins of complex disease, neuropsychiatric disorders, and neurodevelopmental disorders in particular. Genomic variability, as it happens, is also the fuel of evolvability. The genomic events that presided over the evolution of the primate and hominid lineages are over-represented in patients with autism and schizophrenia, as well as intellectual disability and epilepsy. That the special qualities of the human genome that drove evolution might, in some way, contribute to neuropsychiatric disorders is a matter of no little interest.