Lazarus Ross, Vercelli Donata, Palmer Lyle J, Klimecki Walt J, Silverman Edwin K, Richter Brent, Riva Alberto, Ramoni Marco, Martinez Fernando D, Weiss Scott T, Kwiatkowski David J
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Immunol Rev. 2002 Dec;190:9-25. doi: 10.1034/j.1600-065x.2002.19002.x.
Under selective pressure from infectious microorganisms, multicellular organisms have evolved immunological defense mechanisms, broadly categorized as innate or adaptive. Recent insights into the complex mechanisms of human innate immunity suggest that genetic variability in genes encoding its components may play a role in the development of asthma and related diseases. As part of a systematic assessment of genetic variability in innate immunity genes, we have thus far have examined 16 genes by resequencing 93 unrelated subjects from three ethnic samples (European American, African American and Hispanic American) and a sample of European American asthmatics. Approaches to discovering and understanding variation and the subsequent implementation of disease association studies are described and illustrated. Although highly conserved across a wide range of species, the innate immune genes we have sequenced demonstrate substantial interindividual variability predominantly in the form of single nucleotide polymorphisms (SNPs). Genetic variation in these genes may play a role in determining susceptibility to a range of common, chronic human diseases which have an inflammatory component. Differences in population history have produced distinctive patterns of SNP allele frequencies, linkage disequilibrium and haplotypes when ethnic groups are compared. These and other factors must be taken into account in the design and analysis of disease association studies.
在感染性微生物的选择压力下，多细胞生物进化出了免疫防御机制，大致可分为先天性免疫或适应性免疫。对人类先天性免疫复杂机制的最新见解表明，编码其组成部分的基因中的遗传变异性可能在哮喘及相关疾病的发展中起作用。作为对先天性免疫基因遗传变异性的系统评估的一部分，我们迄今为止通过对来自三个种族样本（欧裔美国人、非裔美国人和西班牙裔美国人）的93名无亲缘关系的受试者以及一组欧裔美国哮喘患者样本进行重测序，研究了16个基因。描述并举例说明了发现和理解变异以及随后开展疾病关联研究的方法。尽管我们测序的先天性免疫基因在广泛的物种中高度保守，但它们显示出个体间存在大量变异，主要形式为单核苷酸多态性（SNP）。这些基因的遗传变异可能在决定对一系列具有炎症成分的常见慢性人类疾病的易感性方面发挥作用。当比较不同种族群体时，群体历史的差异产生了独特的SNP等位基因频率、连锁不平衡和单倍型模式。在疾病关联研究的设计和分析中必须考虑这些因素及其他因素。
