Embryo genome profiling by single-cell sequencing for preimplantation genetic diagnosis in a β-thalassemia family

TY - JOUR

T1 - Embryo genome profiling by single-cell sequencing for preimplantation genetic diagnosis in a β-thalassemia family

AU - Xu, Yanwen

AU - Chen, Shengpei

AU - Yin, Xuyang

AU - Shen, Xiaoting

AU - Pan, Xiaoyu

AU - Chen, Fang

AU - Jiang, Hui

AU - Liang, Yu

AU - Wang, Wei

AU - Xu, Xun

AU - Wang, Jian

AU - Zhang, Xiuqing

AU - Zhou, Canquan

AU - Wang, Jun

N1 - © 2015 American Association for Clinical Chemistry.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

U2 - 10.1373/clinchem.2014.228569

DO - 10.1373/clinchem.2014.228569

M3 - Journal article

C2 - 25722458

SN - 0009-9147

VL - 61

SP - 617

EP - 626

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 4

ER -