A Single-Tube Quantitative High-Resolution Melting Curve Method for Parent-of-Origin Determination of 15q Duplications
A Single-Tube Quantitative High-Resolution Melting Curve Method for Parent-of-Origin Determination of 15q Duplications
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DOI：
10.1089/gtmb.2010.0030
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发表时间：
2010-08-01
影响因子：
1.4
通讯作者：
Reiter, Lawrence T.
中科院分区：
文献类型：
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作者：
Urraca, Nora;Davis, Lea;Reiter, Lawrence T.
与自闭症相关的最常见的染色体异常是15q11-q13重复。母系来源或遗传的15q基因重复对自闭症表型有很大风险，而父系来源的重复可能不完全渗透或导致其他神经发育问题。因此，确定这种重复的母系和父系来源对于早期干预治疗和对这些家庭进行适当的遗传咨询是很重要的。我们采用了先前的单反应管分析(高分辨率熔化曲线分析)来确定28个间质重复15q样本、一个家系和两个等着丝粒受试者15q重复起源的亲本。我们的方法在92%的独立样本以及家族性遗传重复和两个等着丝粒样本中区分了父母来源。这种方法准确地确定了重复片段的亲本来源，并测量了样本中这些等位基因的剂量。此外，它还可以在亲本DNA不能用于微卫星分析的样本上进行。这种单管检测的发展将使基因检测实验室更容易提供父母原籍信息，并将向临床遗传学家提供有关这些人患自闭症风险的重要信息。
The most common chromosomal abnormalities associated with autism are 15q11-q13 duplications. Maternally derived or inherited duplications of 15q pose a substantial risk for an autism phenotype, while paternally derived duplications may be incompletely penetrant or result in other neurodevelopmental problems. Therefore, the determination of maternal versus paternal origin of this duplication is important for early intervention therapies and for appropriate genetic counseling to the families. We adapted a previous single-reaction tube assay (high-resolution melting curve analysis) to determine the parent of origin of 15q duplications in 28 interstitial duplication 15q samples, one family and two isodicentric subjects. Our method distinguished parent origin in 92% of the independent samples as well as in the familial inherited duplication and in the two isodicentric samples. This method accurately determines parental origin of the duplicated segment and measures the dosage of these alleles in the sample. In addition, it can be performed on samples where parental DNA is not available for microsatellite analysis. The development of this single-tube assay will make it easier for genetic testing laboratories to provide parent-of-origin information and will provide important information to clinical geneticists about autism risk in these individuals.