The genetic study of three population microisolates in South Tyrol (MICROS):: Study design and epidemiological perspectives
The genetic study of three population microisolates in South Tyrol (MICROS):: Study design and epidemiological perspectives
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DOI：
10.1186/1471-2350-8-29
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发表时间：
2007-06-05
影响因子：
--
通讯作者：
Pramstaller, Peter P.
中科院分区：
文献类型：
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作者：
Pattaro, Cristian;Marroni, Fabio;Pramstaller, Peter P.
背景资料：越来越多的证据表明，小的、孤立的人群在发现疾病病因学相关基因方面可以发挥重要作用。由于历史和政治的原因，南蒂罗尔，北方最意大利的地区，包括几个小规模的村庄，仍然孤立了几个世纪。方法：MICROS的研究是一个基于人口的调查三个小，孤立的村庄，其特点是：老定居点;创始人人数少;高内婚制率;缓慢/零人口扩张。在第一阶段（2002/03）家谱数据，筛选问卷，临床测量，血液和尿液样本，和DNA收集了1175名成年志愿者。第二阶段涉及性状诊断、连锁分析和关联研究，目前正在进行中。这些特征的选择是由临床专家驱动的。获得了初步的描述性统计。结果：从参与者开始，重建了50,037名受试者的家谱，可以追溯到17世纪初。在过去的五代中，受试者被聚集在一个7049名受试者的系谱中，加上178个较小的系谱（每个系谱3至85名受试者）。一个显着的概率进行了评估，许多性状的家族聚集，特别是在心血管，神经和呼吸性状。模拟结果表明，当QTL特异性遗传力>= 20%时，MICROS家系具有检测LOD值>= 3的能力。结论：MICROS研究是一个广泛的、持续的、两阶段的调查，旨在表征孟德尔和复杂疾病的遗传流行病学特征。我们的方法，涉及不同的科学学科，是一个有利的战略来定义和研究人口隔离。阿尔卑斯山人群的隔离，以及迄今为止收集的大量数据，使MICROS研究成为许多医学领域疾病研究的强大资源。最近的成功和模拟研究给了我们信心，我们的谱系可以在寻找新的候选基因座和确认现有的候选基因的价值。
Background: There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries.Methods: The MICROS study is a population- based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-I (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken.Results: Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score >= 3 when the QTL specific heritability is >= 20%.Conclusion: The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.