Scheet Paul, Ehli Erik A, Xiao Xiangjun, van Beijsterveldt Catharina E M, Abdellaoui Abdel, Althoff Robert R, Hottenga Jouke Jan, Willemsen Gonneke, Nelson Kelly A, Huizenga Patricia E, Hu Yueshan, Amos Christopher I, Bartels Meike, Groen-Blokhuis Maria M, de Geus Eco J C, Hudziak James J, Davies Gareth E, Boomsma Dorret I
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Twin Res Hum Genet. 2012 Dec;15(6):737-45. doi: 10.1017/thg.2012.61. Epub 2012 Sep 28.
With the desire to assess genetic variation across the lifespan in large-scale collaborative projects, one question is whether inference of copy number (CN) is sensitive to the source of material for deoxyribonucleic acid (DNA) analysis (e.g., blood and buccal) and another question is whether CN is stable as individual sage. Here, we address these questions by applying Affymetrix 6.0 single nucleotide polymorphism (SNP)micro-arrays to 1,472 DNA samples from 710 individuals from the Netherlands Twin Register, including twin and non-twin individuals (372 with buccal and blood derived DNA and 388 with longitudinal data).Similar concordance for CN and genotype inference between samples from the same individual [or from the monozygotic (MZ) co-twins] was found for blood and buccal tissues. There was a small but statistically significant decrease in across-tissue concordance compared with concordance of samples from the same tissue type. No temporal effect was seen on CN variation from the 388 individuals sampled at two time points ranging from 1 to 12 years apart. The majority of our individuals were sampled at age younger than 20 years. Genotype concordance was very high (~ > 99%) between co-twins from 43 MZ pairs. For75 dizygotic (DZ) pairs, was ~65%. CN estimates were highly consistent between co-twins from MZ pairs for both deletions (f?2 ~ 90%) and duplications ( ~ 86%). For DZ, these were similar for within-individual comparisons, but naturally lower between co-twins (~ ~ 50-60%). These results suggest that DNA from buccal samples perform as well as DNA from blood samples on the current generation of micro-array technologies.
在大规模合作项目中，人们希望评估整个生命周期中的基因变异情况。一个问题是拷贝数（CN）推断对脱氧核糖核酸（DNA）分析的材料来源（如血液和口腔拭子）是否敏感，另一个问题是CN是否随个体年龄稳定。在此，我们通过将Affymetrix 6.0单核苷酸多态性（SNP）微阵列应用于来自荷兰双胞胎登记处的710名个体的1472个DNA样本（包括双胞胎和非双胞胎个体，其中372个个体同时有口腔拭子和血液来源的DNA，388个个体有纵向数据）来解决这些问题。在来自同一个体[或同卵双胞胎（MZ）中的双胞胎]的血液和口腔拭子组织样本中，发现CN和基因型推断具有相似的一致性。与来自相同组织类型的样本的一致性相比，跨组织一致性有小幅但具有统计学意义的下降。在相隔1至12年的两个时间点对388名个体进行采样，未发现CN变异存在时间效应。我们的大多数个体是在20岁以下采样的。来自43对MZ双胞胎的双胞胎之间的基因型一致性非常高（约>99%）。对于75对异卵双胞胎（DZ），一致性约为65%。对于MZ双胞胎中的双胞胎，无论是缺失（f?2约为90%）还是重复（约为86%），CN估计值都高度一致。对于DZ双胞胎，个体内比较时情况相似，但双胞胎之间自然较低（约为50 - 60%）。这些结果表明，在当前一代微阵列技术上，口腔拭子样本的DNA与血液样本的DNA表现相当。
