Massively parallel sequencing for chromosomal abnormality testing in trophectoderm cells of human blastocysts.
Preimplantation genetic diagnosis and screening are widely accepted for chromosomal abnormality identification to avoid transferring embryos with genetic defects. Massively parallel sequencing (MPS) is a rapidly developing approach for genome analysis with increasing application in clinical practice. The purpose of this study was to use MPS for identification of aneuploidies and unbalanced chromosomal rearrangements after blastocyst biopsy. Trophectoderm (TE) samples of 38 blastocysts from 16 in vitro fertilization cycles were subjected to analysis. Low-coverage whole genome sequencing was performed using the Illumina HiSeq2000 platform with a novel algorithm purposely created for chromosomal analysis. The efficiency of this MPS approach was estimated by comparing results obtained by an Affymetrix single-nucleotide polymorphism (SNP) array. Whole genome amplification (WGA) products of TE cells were detected by MPS, with an average of 0.07× depth and 5.5% coverage of the human genome. Twenty-six embryos (68.4%) were detected as euploid, while six embryos (15.8%) contained uniform aneuploidies. Four of these (10.5%) were with solely unbalanced chromosomal rearrangements, whereas the remaining two embryos (5.3%) showed both aneuploidies and unbalanced rearrangements. Almost all these results were confirmed by the SNP array, with the exception of one sample, where different sizes of unbalanced rearrangements were detected, possibly due to chromosomal GC bias in array analysis. Our study demonstrated MPS could be applied to accurately detect embryonic chromosomal abnormality with a flexible and cost-effective strategy and higher potential accuracy.
BGI-Shenzhen, Shenzhen, China.
XuYang
X
Yin
Ke
K
Tan
Gábor
G
Vajta
Hui
H
Jiang
YueQiu
Y
Tan
ChunLei
C
Zhang
Fang
F
Chen
ShengPei
S
Chen
ChunSheng
C
Zhang
XiaoYu
X
Pan
Chun
C
Gong
XuChao
X
Li
ChuYu
C
Lin
Ya
Y
Gao
Yu
Y
Liang
Xin
X
Yi
Feng
F
Mu
LiJian
L
Zhao
HuanHuan
H
Peng
Bo
B
Xiong
ShuoPing
S
Zhang
DeHua
D
Cheng
GuangXiu
G
Lu
XiuQing
X
Zhang
Ge
G
Lin
Wei
W
Wang
D000328:Adult; D000782:Aneuploidy; D001755:Blastocyst; D002869:Chromosome Aberrations; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019836:Preimplantation Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity