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Karyomapping – A Comprehensive Preimplantation Test

Alan Thornhill, Ph.D.
| Mar 06, 2014

Testing embryos to avoid genetic disease is not a new idea, but has roots in decades of previous work. Bob Edwards, who won the Nobel Prize for his work on in vitro fertilization (IVF), sexed rabbit embryos in the 1960s. The first clinical case of preimplantation genetic diagnosis (PGD) to avoid sex-linked disease was performed in 1989. Given the wide variety of human genetic diseases for which PGD is applicable, and the sheer number of mutations encountered in a single disease, it is not surprising that families have had to wait up to a year for development of a test specific to their unique condition and background. These tests must be sensitive and accurate at the single-cell level, yet have a rapid turnaround time to allow embryos to be transferred within the implantation window.

Karyomapping1 is a comprehensive, off-the shelf test for detecting inherited single-gene disorders in embryos before implantation. By leveraging the power of ~300,000 single nucleotide polymorphisms (SNPs) across the entire genome, karyomapping provides greater accuracy to track genetic conditions than current tests. Karyomapping takes advantage of normal SNP variation and bead-based array technology to generate a high-resolution molecular barcode for each parental chromosome, allowing detection of specific chromosomes carrying the ‘targeted’ mutation in embryos. Since the SNPs in this test are used only as markers, the genome-wide information gained in every test is benign and provides only the intended test result. The current standard of care for a couple requesting PGD involves lengthy test development of between one and six months, and a test using only a handful of linked markers. With at least 50 SNP markers present in each region of interest2, karyomapping promises to deliver a more robust, reliable, and accurate test with rapid access for patients.

For couples at risk of transmitting an inherited single-gene disorder, karyomapping in combination with an IVF cycle allows selection of unaffected embryos for transfer with the aim of achieving an unaffected child. By eliminating the need to develop a specific single-cell sensitive test for each family and each condition, karyomapping dramatically reduces waiting time for test development, lessening patient stress. Benefits extend to physicians as well, as they may now offer PGD for any couple with a single, comprehensive, off-the-shelf test that covers virtually all inherited genetic conditions.

To learn more about karyomapping using the Infinium HumanKaryomap-12 BeadChip, register for our webinar on 3/11/14.

  1. Handyside AH, Harton GL, Mariani B, Thornhill AR, Affara N, et al. (2010) Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes. J Med Genet 47(10): 651–8.
  2. Natesan SA, Bladon AJ, Coskun S, Qubbaj W, Prates R, et al. (2014) Genome-wide karyomapping accurately identified the inheritance of single-gene defects in human preimplantation embryos in vitro. Genet Med (in press).