PurposeSingle-nucleotide polymorphism (SNP) microarrays can easily identify whole-chromosome isodisomy but are unable to detect whole-chromosome heterodisomy. However, most cases of uniparental disomy (UPD) involve combinations of heterodisomy and isodisomy, visualized on SNP microarrays as long continuous stretches of homozygosity (LCSH). LCSH raise suspicion for, but are not diagnostic of, UPD, and reporting necessitates confirmatory testing. The goal of this study was to define optimal LCSH reporting standards.MethodsEighty-nine individuals with known UPD were analyzed using chromosomal microarray. The LCSH patterns were compared with those in a phenotypically normal population to predict the clinical impact of various reporting thresholds. False-positive and -negative rates were calculated at various LCSH thresholds.ResultsTwenty-seven of 84 cases with UPD had no significant LCSH on the involved chromosome. Fifty UPD-positive samples had LCSH of varying sizes: the average size of terminal LCSH was 11.0 megabases while the average size of interstitial LCSH was 24.1 megabases. LCSH in the normal population tended to be much smaller (average 4.3 megabases) and almost exclusively interstitial; however, overlap between the populations was noted.ConclusionWe hope that this work will aid clinical laboratories in the recognition and reporting of LCSH.Genetics in Medicine advance online publication, 22 March 2018; doi:10.1038/gim.2018.24.

中文翻译：

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单亲二体性患者的纯合子模式：SNP 微阵列的检出率和建议的报告阈值。

目的单核苷酸多态性 (SNP) 微阵列可以轻松识别全染色体异二体，但无法检测全染色体异二体。然而，大多数单亲二体 (UPD) 病例涉及异二体和等体的组合，在 SNP 微阵列上显示为纯合子的长连续延伸 (LCSH)。LCSH 引起了对 UPD 的怀疑，但不是对 UPD 的诊断，因此需要进行确认测试。本研究的目的是确定最佳的 LCSH 报告标准。方法使用染色体微阵列分析已知 UPD 的 89 名个体。将 LCSH 模式与表型正常人群中的模式进行比较，以预测各种报告阈值的临床影响。在各种 LCSH 阈值下计算假阳性和阴性率。结果84例UPD患者中有27例受累染色体无明显LCSH。50 个 UPD 阳性样本具有不同大小的 LCSH：末端 LCSH 的平均大小为 11.0 兆碱基，而间质 LCSH 的平均大小为 24.1 兆碱基。正常人群中的 LCSH 往往要小得多（平均 4.3 兆碱基）并且几乎完全是间质的；但是，注意到人群之间的重叠。结论我们希望这项工作将有助于临床实验室识别和报告 LCSH。医学遗传学提前在线出版，2018 年 3 月 22 日；doi:10.1038/gim.2018.24。正常人群中的 LCSH 往往要小得多（平均 4.3 兆碱基）并且几乎完全是间质的；但是，注意到人群之间的重叠。结论我们希望这项工作将有助于临床实验室识别和报告 LCSH。医学遗传学提前在线出版，2018 年 3 月 22 日；doi:10.1038/gim.2018.24。正常人群中的 LCSH 往往要小得多（平均 4.3 兆碱基）并且几乎完全是间质的；但是，注意到人群之间的重叠。结论我们希望这项工作将有助于临床实验室识别和报告 LCSH。医学遗传学提前在线出版，2018 年 3 月 22 日；doi:10.1038/gim.2018.24。