Human Aneuploidy

In Chapter 15, we learned about mitosis, meiosis, and the eukaryotic cell cycle. One of the topics covered is how variation in chromosome numbers and chromosome set numbers can occur. These changes can have significant consequences. Aneuploidy is one form of chromosome number variation in which there is a change in how many particular chromosomes there are. Therefore, the sum of the chromosomes could be a number that is not a multiple of a set. Aneuploidy can lead to congential birth defects as well as miscarriage. Most aneuploidy occurs due to errors in maternal meiosis I, and increased maternal age has an impact on error rates. The term nondisjunction is used frequently during this article. In case you did not know, nondisjunction is when chromosomes fail to separate properly during cell division.

Aneuploidy is both "the leading cause of miscarriage" and "the leading cause of congential birth defects and mental retardation". Research has been conducted on whether or not particular meiotic defects can be connected to aneuploidy or infertility. Most studies have involved males, which is mostly irrelevant to the understanding of human aneuploidy. Pairing of chromosomes, synapsis, and recombination need to be observed as they occur in fetal ovarian tissue. This can be challenging, particularly because there are years separating when the cells are in prophase and when they divide. Studies have been conducted on female oocytes instead to determine if chromosomes are already "set-up to mal-segregate" at the appropriate time. Several groups have concluded that in human oocytes there are high levels of defects during synapsis. This is not enough information to conclude that these defects during prophase relate to human aneuploidy. It needs to be determined whether or not chromosomes that are known to exhibit nondisjunction are also more prone to defects in synapsis and recombination.

A type of aneuploidy that you have most likely heard of before is trisomy, or trisomy 21 in particular. This is also known as Down syndrome.

Recent studies on mice have attempted to recreate the nondisjunctional meisosis and recombinational defects that are present in humans. The oocytes of the offspring of two closely related mice were analyzed and it was discovered that meiotic nondisjunction increased due to disturbance in recombination. In another study, it was discovered that oocyte chiasmata are located closer to the telomeres when maternal age is higher than the norm. This caused the connections between homologous chromosomes to be lost more frequently. Mutations also play a role in improper segregation. Research in these areas has supported the idea that abnormalities during prophase (particularly during synapsis, recomination, and cohesion of sister chromatids) can cause errors during chromosome segregation. Extensive research has also been conducted on pre-disposing factors, such as environment and even in a chemical used during the manufacturing of plastics and resin.

A helpful image displaying aneuploidy caused  by nondisjuncton

The molecular background of meiotic nondisjunction has yet to be discovered, as are the reasons behind the increases in nondisjunction with increasing age. In order for this to occur, in vitro studies need to be used on meiosis, but we first have to produce gametes from stem cells. The collaboration between stem cell researchers and aneuploidy researchers may be beneficial. By looking at both fields, scientists may be able to generate in vitro systems that are capable of producing genetically normal eggs while also discovering why meiosis in human females is frequently faulty.

Click here to see where I found this resource. Click here to access the full article. Thanks for reading this unusually long article. I will make sure to make my next two posts a bit shorter to compensate!