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