Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping
Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping
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DOI：
10.1136/jmedgenet-2011-100372
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发表时间：
2011-12-01
影响因子：
4
通讯作者：
Slater, H. R.
中科院分区：
文献类型：
--
作者：
Bruno, D. L.;White, S. M.;Slater, H. R.
背景：最近的几项研究已经证明了单核苷酸多态性（SNP）阵列用于智力残疾，发育迟缓，自闭症或先天性异常的调查。除了LogR“拷贝数”数据之外，这些阵列还提供SNP基因分型数据，用于基因水平的自体接合性作图、估计低水平的嵌合性、评估长连续纯合性延伸（LCSH）、检测单亲二体性和“自体接合”区域。然而，仍然有一些具体的信息，对临床实用性的基因分型data.Methods分子核型分析，使用SNP阵列，进行了5000临床samples.Results临床显着的“LogR中性”基因分型异常检测在0.5%的情况下。其中1例为嵌合体，12例为低水平染色体嵌合体，11例为与单亲二体性相关的LCSH。此外，基因分型数据揭示了几个LCSH与临床相关的“隐性型”遗传deficiency.Conclusions这些结果表明，SNP基因分型数据的实用性，用于检测临床显着异常，包括嵌合体/嵌合体和隐性孟德尔疾病与同源性。从这些病例中推断出的具有临床意义的低水平嵌合体的发生率表明，迄今为止这一点被低估了，染色体嵌合体经常在缺乏指示性临床特征的情况下发生。临床医生对SNP基因分型数据的日益重视和需求对LCSH的解释提出了重大挑战，特别是在没有详细的表型描述来指导实验室分析的情况下。最后，SNP阵列分析揭示的意外或隐藏的血缘关系的报告引起了潜在的伦理和法律的问题。
Background Several recent studies have demonstrated the use of single nucleotide polymorphism (SNP) arrays for the investigation of intellectual disability, developmental delay, autism or congenital abnormalities. In addition to LogR 'copy number' data, these arrays provide SNP genotyping data for gene level autozygosity mapping, estimating low levels of mosaicism, assessing long continuous stretches of homozygosity (LCSH), detection of uniparental disomy, and 'autozygous' regions. However, there remains little specific information on the clinical utility of this genotyping data.Methods Molecular karyotyping, using SNP array, was performed on 5000 clinical samples.Results Clinically significant 'LogR neutral' genotyping abnormalities were detected in 0.5% of cases. Among these were a single case of chimerism, 12 cases with low level chromosome mosaicism, and 11 cases with an LCSH associated with uniparental disomy. In addition, the genotyping data revealed several LCSH associated with clinically relevant 'recessive type' genetic defects.Conclusions These results demonstrate the utility of SNP genotyping data for detection of clinically significant abnormalities, including chimerism/mosaicism and recessive Mendelian disorders associated with autozygosity. The incidence of clinically significant low level mosaicism inferred from these cases suggests that this has hitherto been underestimated and chromosome mosaicism frequently occurs in the absence of indicative clinical features. The growing appreciation among clinicians and demand for SNP genotyping data poses significant challenges for the interpretation of LCSH, especially where there is no detailed phenotypic description to direct laboratory analysis. Finally, reporting of unexpected or hidden consanguinity revealed by SNP array analysis raises potential ethical and legal issues.