Genomic landscape of a three-generation pedigree segregating affective disorder.
Genomic landscape of a three-generation pedigree segregating affective disorder.
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DOI：
10.1371/journal.pone.0004474
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Bucan, Maja
中科院分区：
文献类型：
--
作者：
Yang, Shuzhang;Wang, Kai;Gregory, Brittany;Berrettini, Wade;Wang, Li-San;Hakonarson, Hakon;Bucan, Maja
双相情感障碍（BPD）是一种常见的精神疾病，具有复杂的遗传模式。除了传统的连锁和关联研究，这需要大样本量，常见和罕见的染色体拷贝数变异（CNVs）在大家庭的分析可能会提供新的见解复杂疾病的遗传易感性。使用具有超过550，000个SNP标记的Illumina HumanHap 550 BeadChip，我们对三代Old Order Amish家系中的46个个体进行了基因分型，其中19个受影响（16个BPD和3个重度抑郁症）和27个未受影响的受试者。使用PennCNV算法，我们确定了50个CNV区域，大小从12到885 kb不等，包含至少10个单核苷酸多态性（SNP）。在可用于组合基因型-表达分析的19个良好表征的CNV区域中，11个（58%）与成纤维细胞或淋巴母细胞样细胞系中这些CNV区域内、部分内或附近的基因表达变化相关，标称P值<0.05。为了进一步研究大家系中CNVs的遗传方式，我们分析了一组位于6 q27，9q21.11，12p13.31和15 q11的四个CNVs，所有这些CNVs都在情感性精神障碍患者中富集。我们还表明，这些变异影响内或附近的重排神经元基因的表达。我们的分析表明，以家庭为基础的研究的共同和罕见的CNVs在许多位点的综合作用，可能是一个有用的方法在精神疾病的疾病易感性的遗传分析。
Bipolar disorder (BPD) is a common psychiatric illness with a complex mode of inheritance. Besides traditional linkage and association studies, which require large sample sizes, analysis of common and rare chromosomal copy number variants (CNVs) in extended families may provide novel insights into the genetic susceptibility of complex disorders. Using the Illumina HumanHap550 BeadChip with over 550,000 SNP markers, we genotyped 46 individuals in a three-generation Old Order Amish pedigree with 19 affected (16 BPD and three major depression) and 27 unaffected subjects. Using the PennCNV algorithm, we identified 50 CNV regions that ranged in size from 12 to 885 kb and encompassed at least 10 single nucleotide polymorphisms (SNPs). Of 19 well characterized CNV regions that were available for combined genotype-expression analysis 11 (58%) were associated with expression changes of genes within, partially within or near these CNV regions in fibroblasts or lymphoblastoid cell lines at a nominal P value <0.05. To further investigate the mode of inheritance of CNVs in the large pedigree, we analyzed a set of four CNVs, located at 6q27, 9q21.11, 12p13.31 and 15q11, all of which were enriched in subjects with affective disorders. We additionally show that these variants affect the expression of neuronal genes within or near the rearrangement. Our analysis suggests that family based studies of the combined effect of common and rare CNVs at many loci may represent a useful approach in the genetic analysis of disease susceptibility of mental disorders.
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影响因子：
3.5
作者：
GLENN, CC;NICHOLLS, RD;DRISCOLL, DJ
通讯作者：
DRISCOLL, DJ
影响因子：
64.8
作者：
HODGKINSON, S;SHERRINGTON, R;BRYNJOLFSSON, J
通讯作者：
BRYNJOLFSSON, J
DOI：
10.1002/ajmg.b.30498
发表时间：
2007-04-05
影响因子：
2.8
作者：
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通讯作者：
Stopkova, Pavla
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
11
作者：
Baum, A. E.;Akula, N.;McMahon, F. J.
通讯作者：
McMahon, F. J.