The Mechanism for Down, Edwards and Patau Syndromes

As a prelude to the next posting, here is a short summary of the mechanisms by which genetic conditions such as Down (trisomy 21) , Edwards (trisomy 18) and Patau (trisomy 13) syndromes can occur. Trisomy refers to the presence of an extra copy of a chromosome beyond the normal pair. Affected individuals may have 47 instead of 46 chromosomes, or may have 46 chromosomes, with one containing duplicate portions of a third.

Each human cell normally has a compliment of 46 chromosomes in 23 pairs. One copy in each pair is from the father and one from the mother. Every time a cell divides (mitosis) duplicates of each are made and this relationship is preserved. Absent mutation (or rare chimeric individuals) , every cell in your body contains the same genetic compliment.

The exception to this, of course is the process by which sex cells (gametes - eggs and sperm) are created for sexual reproduction in the process called meiosis.

Unlike mitosis, meiosis only occurs in testes or ovaries and has two distinct phases that result in daughter cells that differ greatly genetically from the parent cell..

In phase one of meiosis, each chromosome is duplicated prior to the first cellular division. Once duplicated, the chromosome pairs are in close proximity and a critical process occurs that will increase the diversity of chromosomes created by the process. This is called recombination or crossover.
Portions of one arm of a duplicate chromatid overlap, or crossover, with the arm of one of the complementary strands and they switch places. The result will ultimately be a unique chromosome made up of portions from the father's and mother's originals. Since this happens independently in every new gamete produced, the variability is great and the genetic diversity of the offspring will increase.
Phase one of meiosis ends when the cells divide into two cells each with one of the recombinant pairs of chromosomes.

In phase 2 of meiosis, the cells divide a second time and each gamete (egg or sperm) contains a single recombinant copy of each chromosome pair, i.e. 23 chromosomes instead of the typical 46. Because of crossover recombination during phase 1, the individual gametes will differ from each other and from the original copies inherited from this individual's parents.
Later, during reproduction one of these gametes will hopefully fuse with one from the partner creating a zygote that combines one copy of each chromosome from each parent returning the number of chromosomes to 46 in the new individual.

Unfortunately errors sometimes occur during this process. Often the errors create nonviable gametes but some combinations of errors may result in a viable pregnancy. One group of errors are the trisomy syndromes.

As you might imagine errors can occur in either the division of chromosome pairs or in the recombination process.
If the error is in the division of the chromosomes, one gamete of the 4 daughter cells will have an extra copy of a chromosome (24) and one will have none (22). The gamete absent a copy is usually nonviable with the exception of errors affecting the sex chromosomes. In some cases, a gamete having no copy of a y chromosome, can result in a viable zygote that has one X chromosome only (XO Turner syndrome). Gametes with full duplicate copies of a chromosome which create viable zygotes that go to term, will result in individuals with the most severe cases of the respective trisomy syndrome. The most common duplication errors that can go to term involve chromosomes 21, 18, and 13.

If the error is related to crossover recombination, there is a failure to compete a symmetrical transfer of genetic material from one chromatid to another. One will have duplicate DNA from the donor resulting in a hybrid chromosome.
Where and how much material is duplicated, will determine the severity of these incomplete trisomy cases which may present with less severe forms of the syndrome and have significantly different outcomes.