Fertility and Sterility
Volume 97, Issue 2 , Pages 395-401, February 2012

Origins and rates of aneuploidy in human blastomeres

  • Matthew Rabinowitz, Ph.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • School of Engineering, Aeronautics and Astronautics, Stanford, California
    • ,
  • Allison Ryan, Ph.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • ,
  • George Gemelos, Ph.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • ,
  • Matthew Hill, Ph.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • ,
  • Johan Baner, Ph.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • Genome Technology Center, Stanford University, Stanford, California
    • ,
  • Cengiz Cinnioglu, Ph.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • ,
  • Milena Banjevic, Ph.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • ,
  • Dan Potter, M.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • Huntington Reproductive Center, Laguna Hills, California
    • ,
  • Dmitri A. Petrov, Ph.D.

      Affiliations

    • Department of Biology, Stanford University, Stanford, California
    • ,
  • Zachary Demko, Ph.D.

      Affiliations

    • Natera Inc., Gene Security Network, Inc., Redwood City, California
    • Corresponding Author InformationReprint requests: Zachary Demko, Ph.D., Natera, Inc., 2686 Middlefield Road, Suite C, Redwood City, CA 94063.

Received 21 September 2011; received in revised form 22 November 2011; accepted 24 November 2011. published online 22 December 2011.

Objective

To characterize chromosomal error types and parental origin of aneuploidy in cleavage-stage embryos using an informatics-based technique that enables the elucidation of aneuploidy-causing mechanisms.

Design

Analysis of blastomeres biopsied from cleavage-stage embryos for preimplantation genetic screening during IVF.

Setting

Laboratory.

Patient(s)

Couples undergoing IVF treatment.

Intervention(s)

Two hundred seventy-four blastomeres were subjected to array-based genotyping and informatics-based techniques to characterize chromosomal error types and parental origin of aneuploidy across all 24 chromosomes.

Main Outcome Measure(s)

Chromosomal error types (monosomy vs. trisomy; mitotic vs. meiotic) and parental origin (maternal vs. paternal).

Result(s)

The rate of maternal meiotic trisomy rose significantly with age, whereas other types of trisomy showed no correlation with age. Trisomies were mostly maternal in origin, whereas paternal and maternal monosomies were roughly equal in frequency. No examples of paternal meiotic trisomy were observed. Segmental error rates were found to be independent of maternal age.

Conclusion(s)

All types of aneuploidy that rose with increasing maternal age can be attributed to disjunction errors during meiosis of the oocyte. Chromosome gains were predominantly maternal in origin and occurred during meiosis, whereas chromosome losses were not biased in terms of parental origin of the chromosome. The ability to determine the parental origin for each chromosome, as well as being able to detect whether multiple homologs from a single parent were present, allowed greater insights into the origin of aneuploidy.

Key Words: Aneuploidy, preimplantation genetic diagnosis, microarray, molecular karyotyping, segmental errors

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 D.A.P. has received consulting fees and grants from, and owns stock or stock options in, Gene Security Network. M.R. has nothing to disclose. A.R. has nothing to disclose. G.G. has nothing to disclose. M.H. has nothing to disclose. J.B. has nothing to disclose. C.C. has nothing to disclose. M.B. has nothing to disclose. D.P. has nothing to disclose. Z.D. has nothing to disclose.

 This work was funded in part by grants (2R44HD054958 and 2R44HD060423) from the United States National Institute of Child Health and Human Development.

PII: S0015-0282(11)02810-X

doi:10.1016/j.fertnstert.2011.11.034

Fertility and Sterility
Volume 97, Issue 2 , Pages 395-401, February 2012

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