QUESTION about chromosome translocation (MCAT Bio)

Question

*A child is born with a number of unusual phenotypic features and genetic testing is performed. The child is determined to have partial trisomy 21, with three copies of some segments of DNA from chromosome 21 and a partial monosomy 4, with only one copy of some segments of DNA from chromosome 4. Which of the following mutations could have occurred in one of the parental gametes during development to explain both findings?* The answer is translocation. The answer key says that "translocation between chromosomes 4 and 21 during development of egg or sperm could have lead to this. If part of chromosome 21 was swapped with part of chromosome 4, then a gamete resulting from meiosis in this cell would lead to **daughter cell with two copies of some of the DNA from 21 and no copies of some of the DNA from 4**." I don't understand the part in bold. Why would you get no copies of some of the DNA from 4? Can someone please explain this in detail?

Answer 1

I can help here! In about 4% of Down Syndrome cases, a Robertsonian translocation occurs between chromosomes 14 and 21. In most cases of Down syndrome, non-disjunction occurs (3 copies of the full chromosome 21).

What your question describes is an even rarer form, involving a balanced translocation between 4 and 21.

In a Robertsonian translocation, such as that between 14 and 21, a very large chromosome is formed containing material from both chromosomes 14 and 21. A tiny fragment is also formed, which is lost. This large chromosome may be recognized by the cell as chromosome 14 depending on what parts of DNA remain. Thus, a gamete can contain this translocation chromosome and a copy of normal chromosome 21, meaning there are two copies of chromosome 21's genetic material.

In a balanced translocation, as in your question, a chromosome with a "normal" amount of genetic material is formed. One resultant chromosome contains most of chromosome 4's material and almost none of 21's material. The other contains most of chromosome 21's material and almost none of chromosome 4's material. Depending on what part of the DNA was copied, the latter chromosome may still be recognized by the cell as chromosome 4 despite having almost none of the genetic information of chromosome 4.

Thus some gametes contain a translocation chromosome, with most of chromosome 21 and almost none of chromosome 4, IN ADDITION to a normal copy of chromosome 21 (the other copy, which did not undergo translocation). Thus, there are no copies of DNA from chromosome 4.

This is an exceptionally rare occurence and has generated a case report! See below.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1013425/

Answer 2

Hey -

https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=90&ContentID=P02153

Translocation Down syndrome is a type of Down syndrome that is caused when one chromosome breaks off and attaches to another chromosome. In this case, there are three 21 chromosomes but one of the 21 chromosomes is attached to another chromosome. The genetic material from the extra 21 chromosome is what causes the health problems that are caused by Down syndrome. In translocation Down syndrome, the extra 21 chromosome may be attached to the 14 chromosome, or to other chromosome numbers like 13, 15, or 22. In some cases, two 21 chromosomes can be attached to each other.

A small number of babies born with Down syndrome have translocation Down syndrome. There are no big differences between the patients who have translocation Down syndrome compared with those who have 3 separate copies of chromosome 21. This is called trisomy 21.

Whenever a translocation is found in a child, the parents’ chromosomes are looked at to find out whether the translocation was inherited or not. If one parent has the translocation chromosome, then the healthcare provider knows the baby inherited the translocation from that parent. That parent will actually have 45 total chromosomes in each cell of the body, but the parent will be normal and healthy. This is because that parent still has only two copies of each chromosome, but two of these chromosomes are attached to each other. When a person has a rearrangement of chromosome material with no extra or missing chromosome material, the person is said to have a balanced translocation. That person can also be a balanced translocation carrier.

Parents with balanced translocations may:

1. Have trouble getting pregnant
2. Suffer miscarriages
3. Have an increased chance of having a child with health problems

The parent can donate the right amount of chromosomes to a pregnancy. However, that parent also has a risk of donating too much or too little genetic material to a pregnancy. This is not something the parent can control or predict. The chance depends on the type of chromosome rearrangement and which chromosomes are involved.

There is another important thing to remember when a parent is found to have a translocation. The parents' siblings may also have inherited the translocation and, therefore, may have the same risks for problems with a pregnancy. For this reason, people with chromosome rearrangements should share this information with their relatives so that they can have the option of having their chromosomes studied.