|
Hello to all.
My understanding of RTS (from the conference and a number of papers) is as follows:
When cells divide they
must copy all of the genetic material in the nucleus, so that each daughter cell has a full complement. Our chromosomes are this genetic material. We (ideally) each have 46 chromosomes - 23
pairs. One copy of each pair of chromosomes comes from each parent. That is to say that in the beginning (fertilization) the egg has 23 chromosomes, and the sperm has 23 chromosomes. They are
the only cells that have only 23 chromosomes. The fertilized egg then has 46 chromosomes. An amazing chain of events begins at fertilization. This single cell divides many times, and the
right genes do the right things and eventually you get a baby.
Chromosomes are made of long chains nucleic acids (A, G, C, T are the abbreviations for the nucleic acids that are in
DNA/chromosomes). These nucleic acids bond in pairs A to T and C to G. The structure of these nucleic acids is what gives DNA it's double-helix shape. A particular sequence of nucleic acids
defines a gene. There is a start sequence for each gene, then the gene itself, then a stop sequence. Thousands of genes exist on each chromosome.
To quote from "Biology" by
Wessells and Hopson: "If a chromosome were the length of five letters on this page, the single slender DNA molecule it contains would stretch the length of a football field." The
double-helix of paired nucleic acids is tightly wound around proteins called histones. This chain of DNA wrapped around histones then coils about itself like a string being twisted. And as
with a piece of string that continues to be twisted, it kinks upon itself to form super-coils. Suffice it to say that DNA is densely packed by the time it is in the form we usually see in
pictures of chromosomes.
Many things can and do go wrong during the process of copying chromosomes during cell division. Sometimes a piece of one gene can be left out (a deletion), or
a nucleic acid can be copied wrong (a point mutation where a G is replaced with a T, for example), or pieces of two chromosomes may swap places (a translocation), or sometimes an entire
chromosome may be tripled (called trisomy) or even quadrupled (or more). Down Syndrome is also called Trisomy 21 because people with it have 3 copies of chromosome 21.
Most of the
errors in transcription occur in places that don't really matter - but it is these errors that have led to the diversity in our genes. Each mutation could be an advantage, disadvantage or
neutral in nature. Advantageous and neutral mutations tend to stay around because the carriers live longer and therefore have the opportunity to reproduce more. (Of course this natural
selection happens over many (thousands and millions) of years.)
In the case of RTS, it appears that a mutation occurs on one copy of chromosome 16, in a particular region that contains
the CBP gene. (It would likely be fatal if the mutation occurred in both copies of the gene, because the protein is rather important.) The CBP gene codes for a particular protein that binds
with another protein. Together this protein pair helps to activate a wide-range of other genes. There are other proteins that do similar, and sometimes overlapping, things. Because CBP helps
to activate only SOME other genes, and there are other proteins that activate other genes, the mutation results in the broad array of symptoms that we see in all of our children with RTS.
The type of mutation varies from person to person. Dr. Hennekam indicated that they had discovered all varieties of mutation in their detailed FISH tests - translocations, point
deletions, amino acid swaps.
Because most of the cells in our children have this mutation, they have 50-50 odds of passing it on to their children. Since they each have one good copy
and one bad copy of chromosome 16, half of their eggs or sperm have a good copy.
In the case where members of the same family have RTS, but they are not directly related (as in parent
and child, or grandparent and grandchild), it could be that there is a familial weakness in chromosome 16. That is, there is something about that family's chromosome 16 that predisposes it to
transcriptional errors. But I am just speculating here.
To summarize this rather long-winded explanation: RTS is genetic (as it is caused by a mutation on a chromosome) RTS is
inheritable (as it can be passed from generation to generation) RTS is sporadic (as the mutation occurs randomly - although future research may discover some sort of non-random factor in the
cause of the mutation)
I hope that this isn't too confusing, and that it helped a least a little.
Becky Celuzza
Reference: Wessells, N.K. and J.L. Hopson. Biology. Random
House. 1988. IBSN: 0-394-33732-8
|
