Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches

Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches
复制标题

DOI:
10.1002/ajmg.b.30171
复制
发表时间:
2005-07-05
影响因子:
2.8
通讯作者:
Pato, MT
Pato, MT
中科院分区:
医学3区
文献类型:
--
作者:
Middleton, FA;Pato, CN;Pato, MT

文献摘要

被引文献

相似文献

我们进行了全球RNA转录本分析和综合基因组分析外周血白细胞(PBL)RNA从两组匹配的同胞对不一致的精神分裂症(n = 33同胞对)或双相情感障碍(n = 5同胞对)。用于这些分析的配对选自具有已知遗传连锁模式的家族(精神分裂症为5 q,双相情感障碍为6 q)。在单基因水平上,我们获得了表达变化最显著的转录本列表,并从这些列表中确定了根据这些样本中的诊断对受试者进行分类的预测能力最高的转录本。在基因组水平上,我们全面分析了4,000多个功能组和细胞遗传学位置的成对表达变化,并提出了一种显示这些数据的新方法,我们称之为“细胞基因组”作图。使用定量实时RT-PCR对选定的表达变化进行验证。我们的研究结果为分析PBL RNA在神经精神疾病中表达变化的实用性提供了令人信服的证据。(c)2005 Wiley-Liss,Inc.
We performed global RNA transcript analysis and comprehensive gene group analysis of peripheral blood leukocyte (PBL) RNA from two groups of matched sib-pairs that were discordant for either schizophrenia (n = 33 sib-pairs) or bipolar disorder (n = 5 sib-pairs). The pairs chosen for these analyses were selected from families with known patterns of genetic linkage (5q for schizophrenia and 6q for bipolar disorder). At the single gene level, we obtained lists of the transcripts with the most significant changes in expression and from these lists determined those with the highest degree of predictive power for classifying subjects according to diagnosis in these samples. At the gene group level, we comprehensively analyzed pairwise expression changes of more than 4,000 functional groups and cytogenetic locations, and present a novel method of displaying these data that we term "cytogenomic" mapping. Verification of selected changes in expression was performed using quantitative real-time RT-PCR. Our results provide compelling evidence for the utility of analyzing PBL RNA for changes in expression in neuropsychiatric disorders. (c) 2005 Wiley-Liss, Inc.