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Guest Jill

splice junction mutations

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Guest Jill

hello anyone who reads this.

im a student who is currently writing a research paper on Tay-Sachs disease. I do not have a background in genetics and I am confused on a few details.

 

In one of my sources it says:

"Thirteen splice junction mutations have been documented. Most occur at the intervening sequences at the 5' half of the gene. Only three, IVS-4, -1G-->T, IVS-5, -1G-->T, and IVS-9, -1G-->T occur at 3' splice sites."

 

Questions I have:

a. what is an intervening sequence? is that a fancy name for an intron?

b. what/where is the 5' half of the gene? 3'?

c. what is the meaning of the number after the IVS and what is the meaning of the number (-1) before the G-->T? I'm assuming that G-->T describes a substitution of a guanine for a thymine. Is this a correct assumption?

 

 

Any help you can give would be wonderful. My paper is due on Monday and I'm only having trouble with this one little section!

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a. what is an intervening sequence? is that a fancy name for an intron?

 

Yep

 

b. what/where is the 5' half of the gene? 3'?

 

 

The five carbons in deoxyribose are denoted 1' to 5'.

 

Here's what my bio book has to say:

 

"At one end, denoted the 3' end, a hydroxyl group is attached to the 3' carbon of the terminal deoxyribose. At the opposite end, the 5' end, the sugar-phosphate backbone terminates with the phosphate group attached to the 5' carbon of the last nucleotide."

 

Basically, it helps one orient which side of the nucleic acid chain we're talking about.

 

c. what is the meaning of the number after the IVS and what is the meaning of the number (-1) before the G-->T? I'm assuming that G-->T describes a substitution of a guanine for a thymine. Is this a correct assumption?

 

I'm not sure, I would assume it means Intron-4, Guanine substitutes thymine etc....

 

------

 

Fafalone will be back saturday, he's really good with this stuff and will probably be able to provide more detailed answers.

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This is in a eukaryote, right?

 

In any case i'm having trouble with it as well, even though i know what all the words mean.

 

can you quote any more of the source?

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Guest Jill

yes...eukaryote. the article is about mutations in the HEXA gene of humans that cause Tay-Sachs disease.

 

heres the rest of the section on abnormal splicing:

"Transcripts resulting from allels harboring the splice junction mutations display aberrany splicing and often lack exons germane to the splice site defect. Moreover, the level of mRNA itself is generally very reduced (<1%) due to instability of the defective transcripts. Many species of aberrant transcripts, some lacking exon 12, others lacking upstream exons, are produced from IVS-12, + 1G-->C, the lesion found in 15% of the Ashkenazi Jewish carriers for Tay-Sachs disease. THe IVS-9, + 1G-->A splice site mutation, the predominant Tay-Sachs disease causing aberation in individuals from the British Isles, results in the activation of two cryptic donor splice sites, one in exon 9 and the other in IVS-9."

 

and that's the end of the section. they dont say anything more about it.

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I think the -1 decribes the position of the base relative to the start of the exon, i.e. one base towards the 5' end of the mRNA strand, certainly within the scope of the splicosomes activity. This fits with these mutations causing most of the incidence of the disease.

 

At face value "the 5' half" would mean the half of the mRNA strand closest to the 5' end. It would make more sense for it to mean the 5' end of each exon, but that could just be me jumping to conclusions.

 

Most of my textbooks are still in Cambridge, so i can't check until sunday :(

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