5T, 7T and 9T varient


Super Moderator
I have a great answer, straight from a CFTR genetics analytical scientist at Ambry Genetics.

"Thanks LL for a good background and update for many. Just to clarify about the 5T polymorphism issue. Everyone carries a certain number of T's that are strung together in intron 8 of the CFTR gene. Most people carry 7 or 9, and about 7% of the population carry 5. Right next to this poly T tract is another string of TG's which usually number 10 or 11, and in some cases 12 or 13. When you have 7 or 9 T's the TG number is irrelevant. However, when you have 5T's and it is paired with a higher number of TG's like 12 or 13 this actually acts like another CF mutation. The higher the TG count the more severe the mutation. So if you have a 5T with only 11 is very mild or even asymptomatic. However with 12 or 13 it is more like a moderate CF mutation and when paired with another CF mutation on the other chromosome can actually cause CF. Everybody is different and there is variability with all mutation combinations so you can never predict exactly how the disease will be based on the CF mutations."

To set the stage, the variants you list are technically called T Polymorphisms. In reading the DNA sequencing we are looking to see A's, G's, T's, and C's in some order. A "T" polymorphism is like a genetic stutter. Imagine reading a book and all of a sudden "it" is repeated in the sentence "What does it mean?" To read "What does it it it it it it mean?" is nonsense and a translation of the sentence into another language wouldn't work if you had to try to be faithful to the literal sentence, errors included. Now imagine how difficult it would be if the letters were instructions in a cookie recipe. A smart baker would easily ignore a couple repeated steps but would naturally have difficulty deciding what is really the correct instruction to jump to if there were 9 repeated instructions.

My own sense is what happens during transcription of the gene, when it is templated, turned into something or some process necessary for the cell. Imagine a molecular bus riding over the DNA. If it encounters 2 identical steps it can easily ignore the duplicate. It's a molecule with limited ability and knowledge. Jumping 5, 7, 9 or more could cause the process to go off track. Something like this is happening with the higher T polymorphisms. The information contained in the Ambry explanation is actually concerned with a polymorphism found with higher TG poly's. So, when somebody gets their genetic assay back and are told that they have a 7T, 7T, polymorphism at M470V or such, beware of the possibility of a string of TG's

So a line of code might be ACCTGATTACATTTTTTGTGTGTGTGTGTGTGTGACTTGATAAC... Noting the TTTTT group and the TGTG repeats. Sort of like that molecular bus, cruising along the DNA highway. If the wheels can't span from T to the last stuttered T or worse, the string of TG's, the result can be very much like a mutation. It could be no different in the way a pair of CFTR mutations can cause CF. In some cases of CF, exhaustive genetic testing has left no other conclusion than a mutation like G551D with a 5T polymorphism resulting in Cystic Fibrosis diagnosed from clinical presentation and/or a sweat chloride test.

Hope this helps answer your question, Good Luck,