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World J Med Genet. Apr 27, 2012; 2(2): 9-14
Published online Apr 27, 2012. doi: 10.5496/wjmg.v2.i2.9
Preimplantation testing: Transition from genetic to genomic diagnosis
Eduardo C Lau
Eduardo C Lau, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, United States
Author contributions: Lau EC solely contributed to this paper.
Supported by Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States
Correspondence to: Eduardo C Lau, PhD, Assistant Professor, Department of Pediatrics, Medical College of Wisconsin, TBRC Room C2450, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States. eclau1@gmail.com
Telephone: +1-262-5286668 Fax: +1-866-8690148
Received: February 23, 2012
Revised: April 15, 2012
Accepted: April 20, 2012
Published online: April 27, 2012

Preimplantation genetic testing refers to the procedure to determine the genetic status of embryos formed by in vitro fertilization (IVF) prior to initiating a pregnancy. Traditional genetic methods for preimplantation genetic diagnosis (PGD) examine distinct parts of an individual genome, require the development of a custom assay for every patient family, and are time consuming and inefficient. In the last decade technologies for whole-genome amplification (WGA) from single cells have led to innovative strategies for preimplantation testing. Applications of WGA technology can lead to a universal approach that uses single-nucleotide polymorphisms (SNPs) and mutations across the entire genome for the analysis. Single-cell WGA by multiple displacement amplification has enabled a linkage approach to PGD known as “preimplantation genetic haplotyping”, as well as microarray-based techniques for preimplantation diagnosis. The use of microarrays in preimplantation diagnosis has provided genome-wide testing for gains or losses of single chromosomes (aneuploidies) or chromosomal segments. Properly designed randomized controlled trials are, however, needed to determine whether these new technologies improve IVF outcomes by increasing implantation rates and decreasing miscarriage rates. In genotype analysis of single cells, allele dropout occurs frequently at heterozygous loci. Preimplantation testing of multiple cells biopsied from blastocysts, however, can reduce allele dropout rates and increase the accuracy of genotyping, but it allows less time for PGD. Future development of fast SNP microarrays will enable a universal preimplantation testing for aneuploidies, single-gene disorders and unbalanced translocations within the time frame of an IVF cycle.

Keywords: Preimplantation genetic diagnosis, Single-cell whole genome amplification, Preimplantation genetic haplotyping, Array-comparative genomic hybridization, Single nucleotide polymorphism microarrays