Cook E H
Departments of Psychiatry and Pediatrics, Committees of Genetics and Clinical Pharmacology, University of Chicago, Chicago, Illinois, USA.
Child Adolesc Psychiatr Clin N Am. 2001 Apr;10(2):333-50.
In summary, autism genetics has moved from a time of identification of heritability and determination of risk of "lesser variants" or the "broader phenotype" in relatives to a phase where some cases of autism have a definite basis such as maternally inherited duplications of 15q11-q13, identification of mutations causing AS, Rett syndrome, and FRAXA. The first phase of genome-wide screens has not revealed definitive linkage, but as samples are enlarged and meta-analyses performed, the strongest linkage findings are likely to yield susceptibility variants once fine mapping proceeds. Recent statistical and molecular genetic analysis methods make the additional work feasible. However, frustrating it may be to be in this phase of the research, it is an essential part of the process of moving from identification of heritability in autism to understanding of the disorder in a way that may permit improved treatment in the future. If there is an advantage to autism being a complex rather than monogenic disorder, it is that the nature of multiplicative or interacting genetic risk is that prevention or treatment directed to any of the identified genetic risks may be sufficient to break a chain of pathophysiology. More genes increase the chance that one or more will have implications for treatment development sooner.
总之，自闭症遗传学已从确定遗传力以及确定亲属中“较小变异”或“更广泛表型”风险的阶段，进入到一个新阶段，即某些自闭症病例有明确的病因，如母系遗传的15q11 - q13重复、导致阿斯伯格综合征、雷特综合征和脆性X综合征A的突变的鉴定。全基因组筛查的第一阶段尚未发现明确的连锁关系，但随着样本量的扩大和荟萃分析的开展，一旦精细定位得以推进，最强的连锁发现可能会产生易感性变异。近期的统计和分子遗传学分析方法使进一步的研究工作可行。然而，处于这一研究阶段可能令人沮丧，但它是从确定自闭症遗传力到以一种可能在未来实现更好治疗的方式理解该疾病这一过程的重要组成部分。如果说自闭症是一种复杂而非单基因疾病有什么优势的话，那就是多重或相互作用的遗传风险性质在于，针对任何已确定的遗传风险进行预防或治疗可能足以打破病理生理链。更多的基因增加了这样一种可能性，即其中一个或多个基因将更快地对治疗开发产生影响。
