Karyomapping and how is it improving preimplantation genetics?

Abstract

Introduction: Preimplantation genetic diagnosis and screening (PGD/PGS) has been applied clinically for >25 years however inherent drawbacks include the necessity to tailor each case to the trait in question, and that technology to detect monogenic and chromosomal disorders respectively is fundamentally different.Areas Covered: The area of preimplantation genetics has evolved over the last 25 years, adapting to changes in technology and the need for more efficient, streamlined diagnoses. Karyomapping allows the determination of inheritance from the (grand)parental haplobocks through assembly of inherited chromosomal segments. The output displays homologous chromosomes, crossovers and the genetic status of the embryos by linkage comparison, as well as chromosomal disorders. It also allows for determination of heterozygous SNP calls, avoiding the risks of allele dropout, a common problem with other PGD techniques. Manuscripts documenting the evolution of preimplantation genetics, especially those investigating technologies that would simultaneously detect monogenic and chromosomal disorders, were selected for review.Expert Commentary: Karyomapping is currently available for detection of single gene disorders; ~1000 clinics worldwide offer it (via ~20 diagnostic laboratories) and ~2500 cases have been performed. Due an inability to detect post-zygotic trisomy reliably however and confounding problems of embryo mosaicism, karyomapping has yet to be applied clinically for detection of chromosome disorders.

Karyomapping in Preimplantation Genetic Testing of Patients with Beta-thalassemia and Sickle Cell Anemia

“…This requires patient-and mutationspecific pre-PGT workup, which necessitates a long optimization procedure (13). When there is a second mutation or a need for HLA typing, such optimization becomes even more difficult and time consuming (14). Karyomapping requires only the identification of the informative SNPs before starting the cycle, which can be accomplished by a single run within a week.…”

“…Karyomapping allowed for diagnosis through a single experiment by analyzing both loci separately. The conventional method for two loci PGT requires a long optimization and validation process prior to initiating the cycle (14). Karyomapping can be directly used regardless of mutation type or locus number in the same experiment including HLA typing (11).…”

“…Karyomapping not only determines the disease status of the embryos, but also provides information about chromosomal abnormalities (13). Its main benefit over the direct mutation tests is its applicability to single or multiple regions covered by informative SNP loci with no need for patient-or disease-specific test development from a single experiment (14). Several live births have been reported in cases of PGT following karyomapping used as a diagnostic test (15)(16).…”

The role of prenatal diagnosis following preimplantation genetic testing for single‐gene conditions: A historical overview of evolving technologies and clinical practice

“…This approach increases the number of informative markers to an average of approximately 70 SNPs in the window around the gene of interest, although lower numbers of informative markers are available for certain genes (eg, CFTR , SMN1 ), certain chromosomal regions (genes close to centromeres and telomeres) and in consanguineous couples . Although direct mutation detection is not routinely performed as part of the karyomapping protocol, the method has improved both the laboratory test design process prior to PGT‐M and the overall reliability of the procedure …”

Importance of embryo aneuploidy screening in preimplantation genetic diagnosis for monogenic diseases using the karyomap gene chip

“…Therefore, the chip can be used for PGDs of different monogenic diseases. In addition, a whole-genome SNP chip can simultaneously obtain the results from genotyping and preimplantation genetic screening (PGS) for aneuploidy 6 . Therefore, the karyomap gene chip presents obvious advantages in monogenic disease PGD.…”