Preimplantation genetic haplotyping

Preimplantation genetic haplotyping (PGH) is a clinical method of preimplantation genetic diagnosis (PGD) used to determine the presence of single gene disorders in offspring. PGH provides a more feasible method of gene location than whole-genome association experiments, which are expensive and time-consuming. Preimplantation genetic haplotyping (PGH) is a clinical method of preimplantation genetic diagnosis (PGD) used to determine the presence of single gene disorders in offspring. PGH provides a more feasible method of gene location than whole-genome association experiments, which are expensive and time-consuming. PGH differs from common PGD methods such as fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) for two primary reasons. First, rather than focusing on the genetic makeup of an embryo PGH compares the genome of affected and unaffected members of previous generations. This examination of generational variation then allows for a haplotype of genetic markers statistically associated with the target disease to be identified, rather than searching merely for a mutation. PGH is often used to reinforce other methods of genetic testing, and is considered more accurate than certain more common PGD methods because it has been found to reduce risk of misdiagnoses. Studies have found that misdiagnoses due to allele dropout (ADO), one of the most common causes of interpretation error, can be almost entirely eliminated through use of PGH. Further, in the case of mutation due to translocation, PGH is able to detect chromosome abnormality to its full extent by differentiating between embryos carrying balanced forms of a translocation versus those carrying the homologous normal chromosomes. This is an advantage because PGD methods such as FISH are able to reveal whether an embryo will express the phenotypic difference, but not whether an embryo may be a carrier. In 2015, PGH was used in conjunction with a whole-genome amplification (WGA) process to not only diagnose disease but also distinguish meiotic segregation errors from mitotic ones.