Long tandem repeats as a form of genomic copy number variation: structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populations.
Long tandem repeats as a form of genomic copy number variation: structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populations.
复制标题
DOI：
10.1097/ypg.0b013e3283207ff6
复制
发表时间：
2009-04
影响因子：
0.9
通讯作者：
Margolis RL
中科院分区：
文献类型：
--
作者：
Bruce HA;Sachs N;Rudnicki DD;Lin SG;Willour VL;Cowell JK;Conroy J;McQuaid DE;Rossi M;Gaile DP;Nowak NJ;Holmes SE;Sklar P;Ross CA;Delisi LE;Margolis RL
基因组拷贝数变异（CNVs）是人类基因组中的一种主要变异形式，在多种神经精神疾病中起着病因学作用。串联重复序列，特别是具有长（> 50bp）重复单元的串联重复序列，是相对常见但未被充分研究的CNV类型，其可能显著促进人类基因组变异和疾病风险。因此，我们进行了一项试点实验，以探讨长串联重复序列作为精神疾病的危险因素的潜在作用。采用细菌人工染色体（BAC）阵列比较基因组杂交（aCGH）技术，对34例精神分裂症或情感性精神障碍先证者基因组DNA中的CNV进行检测。aCGH屏幕检测到一个明显的缺失5p15.1在两个先证者，造成的存在下，在每个先证者的两个低拷贝数（短）等位基因的串联重复，范围从< 10 to >50 3.4 kb单位的长度在人口中检查。短等位基因部分分离与精神分裂症在少数家庭，虽然连锁不显着。406例精神分裂症患者和392例对照组的重复长度无显著性差异。虽然我们没有证明5p15.1重复序列与精神分裂症之间的关系，但我们的研究结果表明，长串联重复序列代表了一种有趣的遗传变异类型，以前没有研究过与精神疾病有关的遗传变异。aCGH可以检测这些重复的一个小子集，但系统的研究将需要开发特定的阵列和改进的分析方法。
Genomic copy number variations (CNVs) are a major form of variation in the human genome and play an etiologic role in several neuropsychiatric diseases. Tandem repeats, particularly with long (> 50bp) repeat units, are a relatively common yet underexplored type of CNV that may significantly contribute to human genomic variation and disease risk. We therefore performed a pilot experiment to explore the potential role of long tandem repeats as risk factors in psychiatric disorders. A bacterial artificial chromosome (BAC)-based array comparative genomic hybridization (aCGH) platform was used to examine CNVs in genomic DNA from 34 probands with schizophrenia or schizoaffective disorder. The aCGH screen detected an apparent deletion on 5p15.1 in two probands, caused by the presence in each proband of two low copy number (short) alleles of a tandem repeat that ranges in length from < 10 to > 50 3.4 kb units in the population examined. Short alleles partially segregate with schizophrenia in a small number of families, though linkage was not significant. An association study showed no significant difference in repeat length between 406 schizophrenia cases and 392 controls. Though we did not demonstrate a relationship between the 5p15.1 repeat and schizophrenia, our results illustrate that long tandem repeats represent an intriguing type of genetic variation that have not been previously studied in connection with psychiatric illness. aCGH can detect a small subset of these repeats, but systematic investigation will require the development of specific arrays and improved analytic methods.