A 76-kb duplicon maps close to the BCR gene on chromosome 22 and the ABL gene on chromosome 9: possible involvement in the genesis of the Philadelphia chromosome translocation.
A patient with a typical form of chronic myeloid leukemia was found to carry a large deletion on the derivative chromosome 9q+ and an unusual BCR-ABL transcript characterized by the insertion, between BCR exon 14 and ABL exon 2, of 126 bp derived from a region located on chromosome 9, 1.4 Mb 5' to ABL. This sequence was contained in the bacterial artificial chromosome RP11-65J3, which in fluorescence in situ hybridization experiments on normal metaphases was found to detect, in addition to the predicted clear signal at 9q34, a faint but distinct signal at 22q11.2, where the BCR gene is located, suggesting the presence of a large region of homology between the two chromosomal regions. Indeed, blast analysis of the RP11-65J3 sequence against the entire human genome revealed the presence of a stretch of homology, about 76 kb long, located approximately 150 kb 3' to the BCR gene, and containing the 126-bp insertion sequence. Evolutionary studies using fluorescence in situ hybridization identified the region as a duplicon, which transposed from the region orthologous to human 9q34 to chromosome 22 after the divergence of orangutan from the human-chimpanzee-gorilla common ancestor about 14 million years ago. Recent sequence analyses have disclosed an unpredicted extensive segmental duplication of our genome, and the impact of duplicons in triggering genomic disorders is becoming more and more apparent. The discovery of a large duplicon relatively close to the ABL and BCR genes and the finding that the 126-bp insertion is very close to the duplicon at 9q34 open the question of the possible involvement of the duplicon in the formation of the Philadelphia chromosome translocation.
Saglio
Giuseppe
G
Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy. saglio@csi.it
Storlazzi
Clelia T
CT
Giugliano
Emilia
E
Surace
Cecilia
C
Anelli
Luisa
L
Rege-Cambrin
Giovanna
G
Zagaria
Antonella
A
Jimenez Velasco
Antonio
A
Heiniger
Anabel
A
Scaravaglio
Patrizia
P
Torres Gomez
Antoni
A
Roman Gomez
José
J
Archidiacono
Nicoletta
N
Banfi
Sandro
S
Rocchi
Mariano
M
D000818:Animals; D005075:Biological Evolution; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D011323:Primates / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
D005819:Genetic Markers; D016044:Fusion Proteins, bcr-abl