遗传学
基因座(遗传学)
生物
单倍型
基因
DNA测序
结构变异
基因组
计算生物学
等位基因
人类基因组
作者
Paula J. P. de Vree,Elzo de Wit,Mehmet Birhan Yılmaz,Monique van de Heijning,Petra Klous,Marjon J.A.M. Verstegen,Yi Ching Esther Wan,Hans Teunissen,Peter H.L. Krijger,Geert Geeven,Paul P. Eijk,Daoud Sie,Bauke Ylstra,Lorette O. M. Hulsman,Marieke F. van Dooren,Laura J. C. M. van Zutven,Ans van den Ouweland,Sjef Verbeek,Ko Willems van Dijk,Marion Cornelissen
摘要
Despite developments in targeted gene sequencing and whole-genome analysis techniques, the robust detection of all genetic variation, including structural variants, in and around genes of interest and in an allele-specific manner remains a challenge. Here we present targeted locus amplification (TLA), a strategy to selectively amplify and sequence entire genes on the basis of the crosslinking of physically proximal sequences. We show that, unlike other targeted re-sequencing methods, TLA works without detailed prior locus information, as one or a few primer pairs are sufficient for sequencing tens to hundreds of kilobases of surrounding DNA. This enables robust detection of single nucleotide variants, structural variants and gene fusions in clinically relevant genes, including BRCA1 and BRCA2, and enables haplotyping. We show that TLA can also be used to uncover insertion sites and sequences of integrated transgenes and viruses. TLA therefore promises to be a useful method in genetic research and diagnostics when comprehensive or allele-specific genetic information is needed.
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