Diehl S R, White P S
Craniofacial Epidemiology and Genetics Branch, NIDCR, NIH, Natcher Building Rm 4AS-43G, 45 Center Drive, Bethesda, MD 20892-6401, USA.
Pharmacogenomics. 2001 Feb;2(1):79-84. doi: 10.1517/14622416.2.1.79.
A major goal of pharmacogenomics is to identify the human genetic variation that influences susceptibility to complex diseases. Recently, theoretical statistical analyses have suggested that genes for complex diseases may be found by linkage disequilibrium (i.e., association). Single nucleotide polymorphism (SNP) susceptibility alleles for common diseases can occur at high frequencies in various populations and, thus, have a major impact on morbidity and mortality. To be successful, SNP mapping studies require successful teamwork, integrating clinicians, epidemiologists, molecular genetics experts, laboratory automation engineers, bioinformatics and database experts. New statistical methods are also developing rapidly and promise to further increase the power of these studies. A recent conference on human genetic variation provided an opportunity for experts in all of these disciplines to exchange ideas. At present, great technological challenges need to be overcome in order to increase the throughput greatly while lowering cost and still maintaining high accuracy for SNP genotyping. Although this approach is relatively new (at least on the scale now being contemplated), the large payoffs anticipated to accrue from the successful mapping of SNPs in disease genes has led the area to be very strongly supported by both public and private funding sources. The potential payoff for improving disease diagnosis and therapeutic efficacy, with better avoidance of adverse events based on SNP associations, is providing a tremendous incentive to move this effort forward at an ever-accelerating pace.
药物基因组学的一个主要目标是确定影响复杂疾病易感性的人类基因变异。最近，理论统计分析表明，可以通过连锁不平衡（即关联）来发现复杂疾病的基因。常见疾病的单核苷酸多态性（SNP）易感等位基因在不同人群中可能以高频率出现，因此对发病率和死亡率有重大影响。要取得成功，SNP定位研究需要临床医生、流行病学家、分子遗传学专家、实验室自动化工程师、生物信息学和数据库专家的成功协作。新的统计方法也在迅速发展，并有望进一步提高这些研究的效能。最近召开的一次关于人类基因变异的会议为所有这些学科的专家提供了交流思想的机会。目前，为了大幅提高通量、降低成本并同时保持SNP基因分型的高精度，还需要克服巨大的技术挑战。尽管这种方法相对较新（至少在目前所设想的规模上），但成功定位疾病基因中的SNP有望带来巨大回报，这使得该领域得到了公共和私人资金来源的大力支持。基于SNP关联更好地避免不良事件，从而改善疾病诊断和治疗效果，其潜在回报为以不断加快的速度推进这项工作提供了巨大动力。
