title: Haplotype-based approach for noninvasive prenatal tests of Duchenne muscular dystrophy using cell-free fetal DNA in maternal plasma.
abstract: OBJECTIVE
  This study demonstrates noninvasive prenatal testing (NIPT) for Duchenne muscular dystrophy (DMD) using a newly developed haplotype-based approach.
  
  
  METHODS
  Eight families at risk for DMD were recruited for this study. Parental haplotypes were constructed using target-region sequencing data from the parents and the probands. Fetal haplotypes were constructed using a hidden Markov model through maternal plasma DNA sequencing. The presence of haplotypes linked to the maternal mutant alleles in males indicated affected fetuses. This method was further validated by comparing the inferred single-nucleotide polymorphism (SNP) genotypes to the direct sequencing results of fetal genomic DNA. Prenatal diagnosis was confirmed with amniocentesis, and those results were interpreted in a blinded fashion.
  
  
  RESULTS
  The results showed an average accuracy of 99.98% for the total inferred maternal SNPs. With a mean depth of 30× achieved in the 10-Mb target region of each sample, the noninvasive results were consistent with those of the invasive procedure.
  
  
  CONCLUSIONS
  This is the first report of NIPT for DMD and the first application of a haplotype-based approach in NIPT for X-linked diseases. With further improvements in accuracy, this haplotype-based strategy could be feasible for NIPT for DMD and even other X-linked single-gene disorders.
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Yan
authors: Y
authors: Xu
authors: BGI-Shenzhen, Shenzhen, China.
authors: Xuchao
authors: X
authors: Li
authors: BGI-Shenzhen, Shenzhen, China.
authors: Hui-Juan
authors: HJ
authors: Ge
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Bing
authors: B
authors: Xiao
authors: BGI-Shenzhen, Shenzhen, China.
authors: Yan-Yan
authors: YY
authors: Zhang
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Xiao-Min
authors: XM
authors: Ying
authors: BGI-Shenzhen, Shenzhen, China.
authors: Xiao-Yu
authors: XY
authors: Pan
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors: Lei
authors: L
authors: Wang
authors: BGI-Shenzhen, Shenzhen, China.
authors: Wei-Wei
authors: WW
authors: Xie
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Lin
authors: L
authors: Ni
authors: BGI-Shenzhen, Shenzhen, China.
authors: Sheng-Pei
authors: SP
authors: Chen
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Wen-Ting
authors: WT
authors: Jiang
authors: BGI-Shenzhen, Shenzhen, China.
authors: Ping
authors: P
authors: Liu
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Hui
authors: H
authors: Ye
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Ying
authors: Y
authors: Cao
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Jing-Min
authors: JM
authors: Zhang
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Yu
authors: Y
authors: Liu
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors: Zu-Jing
authors: ZJ
authors: Yang
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Ying-Wei
authors: YW
authors: Chen
authors: BGI-Shenzhen, Shenzhen, China.|Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences of Copenhagen, Section of Molecular Disease Biology, Copenhagen, Denmark.
authors: Fang
authors: F
authors: Chen
authors: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors: Hui
authors: H
authors: Jiang
authors: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors: Xing
authors: http://orcid.org/0000-0002-7135-491X
authors: X
authors: Ji
mesh_terms: D000649:Amniocentesis / Q000379:methods; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
chemical_list: C484258:DMD protein, human; D016189:Dystrophin