用于亨廷顿舞蹈病基因检测的基因组参考物质的开发。

Development of genomic reference materials for Huntington disease genetic testing.

作者信息

Kalman Lisa, Johnson Monique A, Beck Jeanne, Berry-Kravis Elizabeth, Buller Arlene, Casey Brett, Feldman Gerald L, Handsfield James, Jakupciak John P, Maragh Samantha, Matteson Karla, Muralidharan Kasinathan, Richie Kristy L, Rohlfs Elizabeth M, Schaefer Frederick, Sellers Tina, Spector Elaine, Richards C Sue

机构信息

Laboratory Practice Evaluation and Genomics Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

出版信息

Genet Med. 2007 Oct;9(10):719-23. doi: 10.1097/gim.0b013e318156e8c1.

DOI:10.1097/gim.0b013e318156e8c1

PMID:18073586

Abstract

PURPOSE

Diagnostic and predictive testing for Huntington disease requires an accurate measurement of CAG repeats in the HD (IT15) gene. However, precise repeat sizing can be technically challenging, and is complicated by the lack of quality control and reference materials (RM). The aim of this study was to characterize genomic DNA from 14 Huntington cell lines available from the National Institute of General Medical Sciences Human Genetic Cell Repository at the Coriell Cell Repositories for use as reference materials for CAG repeat sizing.

METHODS

Fourteen Huntington cell lines were selected for study. The alleles in these materials represent a large range of sizes that include important diagnostic cutoffs and allele combinations. The allele measurement study was conducted by ten volunteer laboratories using a variety of polymerase chain reaction-based in-house developed methods and by DNA sequence analysis.

RESULTS

The Huntington alleles in the 14 genomic DNA samples range in size from 15 to 100 CAG repeats. There was good agreement among the ten laboratories, and thus, the 95% confidence interval was small for each measurement. The allele size determined by DNA sequence analysis agreed with the laboratory developed tests.

CONCLUSION

These DNA materials, which are available from Coriell Cell Repositories, will facilitate accurate and reliable Huntington genetic testing.

摘要

目的

亨廷顿病的诊断和预测性检测需要准确测量HD（IT15）基因中的CAG重复序列。然而，精确的重复序列大小测定在技术上具有挑战性，并且由于缺乏质量控制和参考材料（RM）而变得复杂。本研究的目的是对来自科里尔细胞库国家普通医学科学研究所人类遗传细胞库的14个亨廷顿细胞系的基因组DNA进行表征，用作CAG重复序列大小测定的参考材料。