Shastry Barkur S
Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
J Hum Genet. 2002;47(11):561-6. doi: 10.1007/s100380200086.
In two randomly selected human genomes, 99.9% of the DNA sequence is identical. The remaining 0.1% of DNA contains sequence variations. The most common type of such variation is called a single-nucleotide polymorphism, or SNP. SNPs are highly abundant, stable, and distributed throughout the genome. These variations are associated with diversity in the population, individuality, susceptibility to diseases, and individual response to medicine. Recently, it has been suggested that SNPs can be used for homogeneity testing and pharmacogenetic studies and to identify and map complex, common diseases such as high blood pressure, diabetes, and heart disease. Consistent with this proposal is the identification of the patterns of SNPs in conditions such as diabetes, schizophrenia, and blood-pressure homeostasis. Although these studies have provided insight into the nature of human sequence variation, it is not known at present whether these variations are truly significant toxicologically and pharmacologically. Moreover, it is possible that most complex, common disorders are caused by the combined effects of multigenes and nongenetic environmental factors (multifactorial). Therefore, it is likely that sequence variation alone is not sufficient to predict the risk of disease susceptibility, particularly in homeostatic organisms like humans. Nevertheless, these variants may provide a starting point for further inquiry.
在随机选取的两个人类基因组中，99.9%的DNA序列是相同的。其余0.1%的DNA包含序列变异。这类变异最常见的类型被称为单核苷酸多态性，即SNP。SNP数量众多、稳定且分布于整个基因组。这些变异与人群多样性、个体性、疾病易感性以及个体对药物的反应有关。最近，有人提出SNP可用于同质性检测和药物遗传学研究，以及识别和定位诸如高血压、糖尿病和心脏病等复杂常见疾病。与这一观点相符的是在糖尿病、精神分裂症和血压稳态等病症中对SNP模式的识别。尽管这些研究为人类序列变异的本质提供了见解，但目前尚不清楚这些变异在毒理学和药理学上是否真的具有重要意义。此外，大多数复杂常见疾病可能是由多基因和非遗传环境因素（多因素）的综合作用引起的。因此，仅序列变异可能不足以预测疾病易感性风险，尤其是在像人类这样的稳态生物体中。然而，这些变异可能为进一步探究提供一个起点。
