Noninvasive prenatal testing for β-thalassemia by targeted nanopore sequencing combined with relative haplotype dosage (RHDO): a feasibility study.
Noninvasive prenatal testing for β-thalassemia by targeted nanopore sequencing combined with relative haplotype dosage (RHDO): a feasibility study.
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通过靶向纳米孔测序结合相对单倍型剂量 (RHDO) 对 β 地中海贫血进行无创产前检测：可行性研究
DOI：
10.1038/s41598-021-85128-2
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发表时间：
2021-03-11
影响因子：
4.6
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Jiang F;Liu W;Zhang L;Guo Y;Chen M;Zeng X;Wang Y;Li Y;Xian J;Du B;Xie Y;Ouyang S;Li S;Yang Y;Zhang C;Luo F;Sun X
单基因疾病的无创产前检测（NIPT）仍然具有挑战性。一种允许精确检测母系遗传等位基因轻微增加的方法是相对单倍型剂量（RHDO）分析，其需要构建亲本单倍型。最近，纳米孔测序技术已经变得可用，并且可能是用于直接构建单倍型的理想工具。在这里，我们探索了在β-地中海贫血的NIPT中将纳米孔测序与RHDO分析相结合的可行性。招募了13个有β-地中海贫血风险的家庭。通过10 kb和20 kb扩增子的远程PCR扩增亲本基因组DNA的靶向区域。使用纳米孔测序和下一代测序数据构建亲本单倍型。利用母体血浆DNA测序数据，通过RHDO分析对父母单倍型的胎儿遗传进行分类。利用10 kb文库的数据对12个家系进行了单倍型定相。而来自20 kb文库的数据给出了更好的性能，在所有13个家族中实现了单倍型定相。13个家庭中有12个家庭的胎儿状态被正确分类。因此，靶向纳米孔测序结合RHDO分析对于β-地中海贫血的NIPT是可行的。
Noninvasive prenatal testing (NIPT) for single gene disorders remains challenging. One approach that allows for accurate detection of the slight increase of the maternally inherited allele is the relative haplotype dosage (RHDO) analysis, which requires the construction of parental haplotypes. Recently, the nanopore sequencing technologies have become available and may be an ideal tool for direct construction of haplotypes. Here, we explored the feasibility of combining nanopore sequencing with the RHDO analysis in NIPT of β-thalassemia. Thirteen families at risk for β-thalassemia were recruited. Targeted region of parental genomic DNA was amplified by long-range PCR of 10 kb and 20 kb amplicons. Parental haplotypes were constructed using nanopore sequencing and next generation sequencing data. Fetal inheritance of parental haplotypes was classified by the RHDO analysis using data from maternal plasma DNA sequencing. Haplotype phasing was achieved in 12 families using data from 10 kb library. While data from the 20 kb library gave a better performance that haplotype phasing was achieved in all 13 families. Fetal status was correctly classified in 12 out of 13 families. Thus, targeted nanopore sequencing combined with the RHDO analysis is feasible to NIPT for β-thalassemia.
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影响因子：
9.3
作者：
Lam, Kwan-Wood G.;Jiang, Peiyong;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis
影响因子：
8.8
作者：
Xu, Yan;Li, Xuchao;Ji, Xing
通讯作者：
Ji, Xing
影响因子：
9.3
作者：
Barrett, Angela N.;McDonnell, Thomas C. R.;Chitty, Lyn S.
通讯作者：
Chitty, Lyn S.
DOI：
10.1038/ejhg.2016.195
发表时间：
2017-04
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Parks M;Court S;Bowns B;Cleary S;Clokie S;Hewitt J;Williams D;Cole T;MacDonald F;Griffiths M;Allen S
通讯作者：
Allen S
影响因子：
46.9
作者：
Jain M;Koren S;Miga KH;Quick J;Rand AC;Sasani TA;Tyson JR;Beggs AD;Dilthey AT;Fiddes IT;Malla S;Marriott H;Nieto T;O'Grady J;Olsen HE;Pedersen BS;Rhie A;Richardson H;Quinlan AR;Snutch TP;Tee L;Paten B;Phillippy AM;Simpson JT;Loman NJ;Loose M
通讯作者：
Loose M