Noninvasive Prenatal Detection of Trisomy 21 by Targeted Semiconductor Sequencing: A Technical Feasibility Study

被引：1

作者：

Xi, Yanwei ^{[1
]}

Arbabi, Aryan ^{[3
,4
]}

McNaughton, Amy J. M. ^{[5
,6
]}

Hamilton, Alison ^{[1
]}

Hull, Danna

Perras, Helene ^{[2
]}

Chiu, Tillie ^{[2
]}

Morrison, Shawna ^{[2
]}

Goldsmith, Claire ^{[2
]}

Creede, Emilie ^{[2
]}

Anger, Gregory J. ^{[8
]}

Honeywell, Christina ^{[2
]}

Cloutier, Mireille ^{[2
]}

Macchio, Natasha ^{[8
]}

Kiss, Courtney ^{[8
]}

Liu, Xudong ^{[5
,6
]}

Crocker, Susan ^{[7
,8
]}

Davies, Gregory A. ^{[7
,8
]}

Brudno, Michael ^{[3
,4
]}

Armour, Christine M. ^{[1
,2
]}

机构：

[1] Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada

[2] Childrens Hosp Eastern Ontario, Reg Genet Unit, Ottawa, ON, Canada

[3] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada

[4] Hosp Sick Children, Ctr Computat Med, Toronto, ON, Canada

[5] Queens Genom Lab Ongwanada, Kingston, ON, Canada

[6] Queens Univ, Dept Psychiat, Kingston, ON, Canada

[7] Queens Univ, Kingston, ON, Canada

[8] Kingston Gen Hosp, Kingston, ON, Canada

来源：

FETAL DIAGNOSIS AND THERAPY | 2017年 / 42卷 / 04期

关键词：

Noninvasive prenatal testing; Cell-free fetal DNA; Semiconductor sequencing; Targeted sequencing; Trisomy; 21; CELL-FREE DNA; FREE FETAL DNA; MATERNAL PLASMA; TRISOMIES; 21; ANEUPLOIDY; IMPLEMENTATION; PERFORMANCE; BLOOD;

D O I：

10.1159/000460248

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

Objective: To develop an alternate noninvasive prenatal testing method for the assessment of trisomy 21 (T21) using a targeted semiconductor sequencing approach. Methods: A customized AmpliSeq panel was designed with 1,067 primer pairs targeting specific regions on chromosomes 21, 18, 13, and others. A total of 235 samples, including 30 affected with T21, were sequenced with an Ion Torrent Proton sequencer, and a method was developed for assessing the probability of fetal aneuploidy via derivation of a risk score. Results: Application of the derived risk score yields a bimodal distribution, with the affected samples clustering near 1.0 and the unaffected near 0. For a risk score cutoff of 0.345, above which all would be considered at "high risk," all 30 T21-positive pregnancies were correctly predicted to be affected, and 199 of the 205 non-T21 samples were correctly predicted. The average hands-on time spent on library preparation and sequencing was 19 h in total, and the average number of reads of sequence obtained was 3.75 million per sample. Conclusion: With the described targeted sequencing approach on the semiconductor platform using a custom-designed library and a probabilistic statistical approach, we have demonstrated the feasibility of an alternate method of assessment for fetal T21. (c) 2017 S. Karger AG, Basel

引用

页码：302 / 310

页数：9

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