Understanding How UPD Happens
UPD most often happens after an error in the process of making sperm or eggs. Typically, to make sperm and eggs, the chromosome pairs all divide in half, so that each egg has one member of each chromosome pair, and the same process happens in the sperm. This way, at conception, the embryo has two copies of each chromosome, one from each parent. Sometimes, however, there is an error in packaging and the two chromosomes from the pair are packaged together in an egg or sperm. After fertilization, that embryo then either has an extra chromosome or a missing chromosome, which can cause difficulties with the embryo’s development. The embryo’s cells can try to correct this by either losing an extra chromosome or making a copy of the chromosome that is missing.
Sometimes the chromosomes do not divide correctly when making a sperm or egg, which results in an embryo with a missing copy of a chromosome. In this graphic, the egg does not have any chromosome 15s. The cells in the embryo can try to correct this through a process by making a copy of the remaining chromosome, which is called monosomic rescue. This results in a type of UPD called isodisomy.
Sometimes the chromosomes do not divide correctly when making a sperm or egg, which results in an embryo with an extra copy of a chromosome. In this graphic, the chromosome 15s did not divide when the sperm was being made.
The cells in the embryo can try to correct this through a process called trisomic rescue, where one of the chromosomes is lost. Depending upon which chromosome is lost, this can cause UPD.
More rarely, a parent carries a chromosome rearrangement that increases the chance for UPD. Shown here is one possible rearrangement that can increase the chance of UPD 15 greatly, where two chromosome 15s stuck together.
At conception, the embryo has an extra copy of the chromosome. An embryo with three copies of chromosome 15 will not survive. However, if the maternal chromosome 15 is lost, the embryo can continue developing. This embryo has only chromosome 15s from the sperm, so has UPD.
Typically, UPD is a random event that occurred in the formation of the sperm or egg, or early in the development of an embryo. It is not caused by anything a parent did or did not do before conception or during the pregnancy.
However, sometimes UPD is the result of a chromosome difference in a parent that makes UPD more likely to occur. Consequently, chromosomal testing of the parents is recommended. If the parents have chromosomal testing that is typical, the chance for a future child to have UPD that causes AS is predicted to be less than 1%. This means that at least 99% of the time, future children will not have UPD that causes AS. This chance is not zero because rare cases have been reported where chromosome 15 is more likely to be packaged incorrectly when eggs are made, resulting in an increased chance for UPD. If a parent has a chromosomal difference, the chance will depend on the specific chromosomal difference.