scHaplotyper: haplotype construction and visualization for genetic diagnosis using single cell DNA sequencing data.

Autor: Yan Z; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China., Zhu X; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China., Wang Y; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China., Nie Y; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China., Guan S; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China., Kuo Y; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China., Chang D; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China., Li R; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China., Qiao J; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China.; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.; Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, 100871, China., Yan L; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China. yanliyingkind@aliyun.com.; Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China. yanliyingkind@aliyun.com.; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, 100191, China. yanliyingkind@aliyun.com.
Jazyk: angličtina
Zdroj: BMC bioinformatics [BMC Bioinformatics] 2020 Feb 01; Vol. 21 (1), pp. 41. Date of Electronic Publication: 2020 Feb 01.
DOI: 10.1186/s12859-020-3381-5
Abstrakt: Background: Haplotyping reveals chromosome blocks inherited from parents to in vitro fertilized (IVF) embryos in preimplantation genetic diagnosis (PGD), enabling the observation of the transmission of disease alleles between generations. However, the methods of haplotyping that are suitable for single cells are limited because a whole genome amplification (WGA) process is performed before sequencing or genotyping in PGD, and true haplotype profiles of embryos need to be constructed based on genotypes that can contain many WGA artifacts.
Results: Here, we offer scHaplotyper as a genetic diagnosis tool that reconstructs and visualizes the haplotype profiles of single cells based on the Hidden Markov Model (HMM). scHaplotyper can trace the origin of each haplotype block in the embryo, enabling the detection of carrier status of disease alleles in each embryo. We applied this method in PGD in two families affected with genetic disorders, and the result was the healthy live births of two children in the two families, demonstrating the clinical application of this method.
Conclusion: Next generation sequencing (NGS) of preimplantation embryos enable genetic screening for families with genetic disorders, avoiding the birth of affected babies. With the validation and successful clinical application, we showed that scHaplotyper is a convenient and accurate method to screen out embryos. More patients with genetic disorder will benefit from the genetic diagnosis of embryos. The source code of scHaplotyper is available at GitHub repository: https://github.com/yzqheart/scHaplotyper.
Databáze: MEDLINE
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