title: Detection and quantitation of chromosomal mosaicism in human blastocysts using copy number variation sequencing.
abstract: OBJECTIVE
  Currently, our understanding of the nature and reproductive potential of blastocysts associated with trophectoderm (TE) lineage chromosomal mosaicism is limited. The objective of this study was to first validate copy number variation sequencing (CNV-Seq) for measuring the level of mosaicism and second, examine the nature and level of mosaicism in TE biopsies of patient's blastocysts.
  
  
  METHODS
  TE biopy samples were analysed by array comparative genomic hybridization (CGH) and CNV-Seq to discriminate between euploid, aneuploid and mosaic blastocysts.
  
  
  RESULTS
  Using artificial models of TE mosaicism for five different chromosomes, CNV-Seq accurately and reproducibly quantitated mosaicism at levels of 50% and 20%. In a comparative 24-chromosome study of 49 blastocysts by array CGH and CNV-Seq, 43 blastocysts (87.8%) had a concordant diagnosis and 6 blastocysts (12.2%) were discordant. The discordance was attributed to low to medium levels of chromosomal mosaicism (30-70%) not detected by array CGH. In an expanded study of 399 blastocysts using CNV-Seq as the sole diagnostic method, the proportion of diploid-aneuploid mosaics (34, 8.5%) was significantly higher than aneuploid mosaics (18, 4.5%) (p < 0.02).
  
  
  CONCLUSIONS
  Mosaicism is a significant chromosomal abnormality associated with the TE lineage of human blastocysts that can be reliably and accurately detected by CNV-Seq.
authors.affiliation: Safe Fertility Center, Bangkok, Thailand.
authors.forename: Tida
authors.initials: T
authors.lastname: Ruttanajit
authors.affiliation: Safe Fertility Center, Bangkok, Thailand.
authors.forename: Sujin
authors.initials: S
authors.lastname: Chanchamroen
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.|Berry Genomics, C., Limited, Beijing, China.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
authors.affiliation: Safe Fertility Center, Bangkok, Thailand.
authors.forename: Kritchakorn
authors.initials: K
authors.lastname: Sawakwongpra
authors.affiliation: Safe Fertility Center, Bangkok, Thailand.
authors.forename: Wanwisa
authors.initials: W
authors.lastname: Suksalak
authors.affiliation: Berry Genomics, C., Limited, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Leng
authors.affiliation: Department of Obstetrics and Gynecology, PLA General Hospital, Beijing, China.
authors.forename: Junmei
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynecology, PLA General Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, PLA General Hospital, Beijing, China.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Safe Fertility Center, Bangkok, Thailand.
authors.forename: Wiwat
authors.initials: W
authors.lastname: Quangkananurug
mesh_terms: D001755:Blastocyst / Q000378:metabolism*; D055028:Comparative Genomic Hybridization; D015925:Cryopreservation; D056915:DNA Copy Number Variations / Q000235:genetics*; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics; D004624:Embryo Transfer; D005260:Female; D006801:Humans; D009030:Mosaicism; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods; D014327:Trophoblasts / Q000378:metabolism; D014424:Turner Syndrome / Q000175:diagnosis* / Q000235:genetics