Plomin Robert
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
J Child Psychol Psychiatry. 2005 Oct;46(10):1030-8. doi: 10.1111/j.1469-7610.2005.01524.x.
The seven papers in this special section chart where we are in the quest for quantitative trait loci (QTLs) in key areas of child psychology and psychiatry such as reading and hyperactivity. But we are not there yet.
This commentary considers some new developments that are likely to accelerate the journey towards the identification of QTLs.
The single most important factor is the need for very large samples to attain adequate power to detect and replicate QTLs of very small effect size. Another important development is the microarray, which makes it possible to genotype hundreds of thousands of SNPs simultaneously. Using microarrays in association studies allows SNPs across the whole genome to be genotyped. Microarrays will boost power even more when they contain all functional polymorphisms in the genome, including functional non-coding DNA.
Once replicable QTLs are identified in areas such as reading and hyperactivity, the real journey will begin. Future studies will use sets of QTLs as genetic risk indicators in top-down behavioural genomic research, leading to gene-based diagnoses, gene-based treatments tailored to the individual, and early warning systems and interventions. These discoveries will eventually help to prevent or at least ameliorate childhood disorders before they cast their long shadow over development.
本专题中的七篇论文描绘了我们在儿童心理学和精神病学关键领域(如阅读和多动)寻找数量性状基因座(QTL)的进展情况。但我们尚未达成目标。
本评论探讨了一些可能加速QTL鉴定进程的新进展。
最重要的单一因素是需要非常大的样本量,以获得足够的检验效能来检测和复制效应量极小的QTL。另一个重要进展是微阵列,它使同时对数十万单核苷酸多态性(SNP)进行基因分型成为可能。在关联研究中使用微阵列可对全基因组的SNP进行基因分型。当微阵列包含基因组中的所有功能多态性,包括功能性非编码DNA时,其检验效能将进一步提高。
一旦在阅读和多动等领域鉴定出可复制的QTL,真正的征程才将开始。未来的研究将把QTL集用作自上而下的行为基因组研究中的遗传风险指标,从而实现基于基因的诊断、针对个体的基因治疗,以及早期预警系统和干预措施。这些发现最终将有助于在儿童疾病对发育造成长期影响之前预防或至少改善这些疾病。