Philadelphia Chromosome Sequence
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9.7 years ago
Ma ▴ 140

Hi: I know that the philadelphia chromosome is a chimeric chromosome that is formed by the translocation of BCR and ABL from chromosomes 22 and 9; that it forms a mutant 22 chromosome. I would like to perform some comparisons with a normal chromosome 22, but with the nucleotide sequences of both. I have found the complete sequence of the chromosome 22, the fasta sequence of BCR and of ABL, but not of a sample of a philadelphia chromosome. Does anyone knows where I can download one or how I could simulate one? Thanks

cancer chromosome • 4.4k views
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9.7 years ago

Good question!

I used to work on BCR-ABL and so took an interest to find some info on this question. It is also pertinent beyond BCR-ABL, of course.

So, BCR is named for breakpoint cluster region. Thus, there is not one single gene fusion, but many. In my hunting I saw reference to BCR-BCL and BCR-FGFR1. There is more than one BCR-ABL sequence.

Go to NCBI and use the search term "BCR-ABL" at CancerChromosomes. This looks like some good and useful entries are returned.

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No, don't do it that way. Take the altered BCR-ABL fusion genes and fuse them to their respective chromosome ends and build your fusion chromosome in 3 pieces: the intact parts of 9 and 22 + the BCR-ABL fusion. As there are many BCR-ABL fusions possible/reported for the different leukemias, you'll have several BCR-ABL seqs to plug into the 9 and 22 ends. No one who manages genome seq data would ever keep all these (plus thousands of other) chromosome fusion products - just the instructions on how to build them.

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Download 9 and 22 intact. Cut each one at the respective oncogene, BCR and ABL in a manner that matches known BCR-ABL fusions. Make the join. Because the chromosomes are large, bulky data file not easily edited in such a manner, you could work on the BCR-ABL portion alone and then splice that into the receiving portions of 9 and 22.

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In particular, it looks like the Mitelman database (returned in the above query) may have info you'd like.

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thanks for the reply, but for example in ftp://ftp.ncbi.nih.gov/genomes/H_sapiens/CHR_22/ I found that the size of the chromosome 22 in fasta is 9.6 Mb (hs_alt_HuRef_chr22.fa.gz), but the fusion of BCR is 137 Kb and ABL is 173 kb, so even if I join them I would not get a complete mutated chromosome 22. I really need the complete sequence of this mutated chromosome to compared it with a normal chromosome 22; so for that reason it should be on size almost similar, how much is the size of a philadelphia chromosome in mb? thanks you so much

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hi @Larry_Parnell, I have downloaded the fasta seq of BCR and ABL genes from NCBI, I also got the sequences of the Chromosome 9 and 22; so what I have done is to put in one file the both the BCR and the ABL, then I have added this to the last part of the chromosome 22, is that right? because I was wondering if in this case I would not have two parts of the BCR in chr22, one that was already there and another one of the fasta file that I have just added, or is another way around? thanks

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9.7 years ago

You might take a look at ChimerDB which includes a search function based on gene with links to papers and sometimes next-gen sequencing data.

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