Conventional next‐generation sequencing methods, used in most gene panels, cannot separate maternally and paternally derived sequence information of distant variants. In recessive diseases, two or more equally plausible causative variants with unsolved phase information prevent accurate molecular diagnosis. In reality, close relatives might be unavailable for segregation analysis. Here, we utilized whole genome linked‐read sequencing to assign variants to haplotypes in two patients with inherited retinal dystrophies. Patient 1 with macular dystrophy had variants c.3442T>C, p.(Cys1148Arg), c.4209G>T, p.(Glu1403Asp), and c.1182C>T, p.(Cys394=) in CRB1, and Patient 2 with nonsyndromic retinitis pigmentosa had c.1328T>A, p.(Val443Asp) and c.3032C>G, p.(Ser1011*) in AHI1. The relatives were not available for genotyping. Using whole genome linked‐read sequencing we phased the variants to haplotypes providing genetic background for the retinal dystrophies. In future, when the price of sequencing methods that provides long‐read data decreases and their read‐depth and accuracy increases, they are probably considered the primary or adjunctive sequencing methods in genetic testing, allowing the immediate collection of phase information and thus obviating the need for the carrier testing and segregation analysis.

中文翻译：

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使用全基因组连锁读取测序识别隐性遗传性视网膜营养不良的单倍型。

大多数基因组中使用的传统下一代测序方法无法分离远距离变异的母本和父本衍生的序列信息。在隐性疾病中，两个或更多具有未解决相位信息的同样合理的致病变异会妨碍准确的分子诊断。实际上，近亲可能无法进行隔离分析。在这里，我们利用全基因组链接读取测序为两名遗传性视网膜营养不良患者的单倍型分配变异。患有黄斑营养不良的患者 1 在CRB1和患者 2 中具有变体 c.3442T>C、p.(Cys1148Arg)、c.4209G>T、p.(Glu1403Asp) 和 c.1182C>T、p.(Cys394=)与非综合征性色素性视网膜炎中有c.1328T> A，第（Val443Asp）和c.3032C> G，p。（Ser1011 *）AHI1. 亲属无法进行基因分型。使用全基因组链接读取测序，我们将变异分阶段为单倍型，为视网膜营养不良提供遗传背景。未来，当提供长读长数据的测序方法价格下降，读长深度和准确度增加时，它们可能被认为是基因检测中的主要或辅助测序方法，允许立即收集相位信息，从而避免需要进行载体测试和分离分析。