Embryo genome profiling by single-cell sequencing for preimplantation genetic diagnosis in a β-thalassemia family.
BACKGROUND
The embryonic genome, including genotypes and haplotypes, contains all the information for preimplantation genetic diagnosis, representing great potential for mendelian disorder carriers to conceive healthy babies.


METHODS
We developed a strategy to obtain the full embryonic genome for a β-thalassemia-carrier couple to have a healthy second baby. We carried out sequencing for single blastomere cells and the family trio and further developed the analysis pipeline, including recovery of the missing alleles, removal of the majority of errors, and phasing of the embryonic genome.


RESULTS
The final accuracy for homozygous and heterozygous single-nucleotide polymorphisms reached 99.62% and 98.39%, respectively. The aneuploidies of embryos were detected as well. Based on the comprehensive embryonic genome, we effectively performed whole-genome mendelian disorder diagnosis and human leukocyte antigen matching tests.


CONCLUSIONS
This retrospective study in a β-thalassemia family demonstrates a method for embryo genome recovery through single-cell sequencing, which permits detection of genetic variations in preimplantation genetic diagnosis. It shows the potential of single-cell sequencing technology in preimplantation genetic diagnosis clinical practices.
First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong, China;
Yanwen
Y
Xu
BGI-Shenzhen, Shenzhen, China; Shenzhen Municipal Key Laboratory of Birth Defects Screening and Engineering, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Diseases Genome, Guangdong, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China;
Shengpei
S
Chen
BGI-Shenzhen, Shenzhen, China; Shenzhen Municipal Key Laboratory of Birth Defects Screening and Engineering, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Diseases Genome, Guangdong, China;
Xuyang
X
Yin
First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong, China;
Xiaoting
X
Shen
BGI-Shenzhen, Shenzhen, China; Shenzhen Municipal Key Laboratory of Birth Defects Screening and Engineering, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Diseases Genome, Guangdong, China; School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China;
Xiaoyu
X
Pan
BGI-Shenzhen, Shenzhen, China; Shenzhen Municipal Key Laboratory of Birth Defects Screening and Engineering, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Diseases Genome, Guangdong, China; Section of Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
Fang
F
Chen
BGI-Shenzhen, Shenzhen, China; Shenzhen Municipal Key Laboratory of Birth Defects Screening and Engineering, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Diseases Genome, Guangdong, China; Department of Biology, University of Copenhagen, Copenhagen, Denmark;
Hui
H
Jiang
BGI-Shenzhen, Shenzhen, China;
Yu
Y
Liang
BGI-Shenzhen, Shenzhen, China; Shenzhen Municipal Key Laboratory of Birth Defects Screening and Engineering, Shenzhen, China;
Wei
W
Wang
BGI-Shenzhen, Shenzhen, China;
Xun
X
Xu
BGI-Shenzhen, Shenzhen, China;
Jian
J
Wang
BGI-Shenzhen, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Diseases Genome, Guangdong, China; zhangxq@genomics.org.cn zhoucanquan@hotmail.com wangj@genomics.org.cn.
Xiuqing
X
Zhang
First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong, China; zhangxq@genomics.org.cn zhoucanquan@hotmail.com wangj@genomics.org.cn.
Canquan
C
Zhou
BGI-Shenzhen, Shenzhen, China; Department of Biology, University of Copenhagen, Copenhagen, Denmark; King Abdulaziz University, Jeddah, Saudi Arabia; The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen. zhangxq@genomics.org.cn zhoucanquan@hotmail.com wangj@genomics.org.cn.
Jun
J
Wang
D000328:Adult; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods*; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics* / Q000517:prevention & control
D006680:HLA Antigens; D055544:beta-Globins; D004247:DNA