Comparative Sequence Analysis of a Region on Human Chromosome 13q14, Frequently Deleted in B-Cell Chronic Lymphocytic Leukemia, and Its Homologous Region on Mouse Chromosome 14

Genomics ◽  
2000 ◽  
Vol 70 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Bagrat Kapanadze ◽  
Natalia Makeeva ◽  
Martin Corcoran ◽  
Niclas Jareborg ◽  
Marianne Hammarsund ◽  
...  
Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 295-295
Author(s):  
Rebecca L. Auer ◽  
Sophia Riaz ◽  
Finbarr E. Cotter

Abstract Loss of the long arm of chromosomes 11 and 13 are the most consistent cytogenetic abnormalities for patients with B-cell chronic lymphocytic leukemia (B-CLL). They suggest the presence of as yet unidentified tumor suppressor genes within well defined minimal deleted regions (MDRs). The use of small vertebrate organisms, such as the zebrafish, as models of diseases associated with chromosomal deletions enables the functional analysis of potential causative genes. Hemopoiesis is well conserved between the zebrafish and human and conserved synteny exists between the two genomes. In this study, the evolutionary conservation between the zebrafish and human genome is investigated for the 13q14 and 11q22-23 regions deleted in B-CLL. Zebrafish orthologs have been identified and radiation hybrid (RH) mapping performed to confirm their chromosomal location and define regions of conserved synteny.We have identified 38 zebrafish orthologs of the human genes in the MDRs in zebrafish cDNA and the syntenic regions for the human deletions in the zebrafish genome. The 13q14 region was syntenic with two main regions in the zebrafish genome, namely linkage group 1 (LG1) and LG9. The majority of zebrafish orthologs to 11q22-23 were found on LG5, LG15 and LG21. One syntenic region, LG9, in the zebrafish genome is of potential interest. Analysis of the smallest critical region of deletion in B-CLL for both 11q22-23 and 13q14 reveals that the human gene equivalents are contained within an area of 22.02 cR on LG9 (approximately 3260 kb). Within LG9, orthologs to two genes to human chromosome 11, three to human chromosome 13 and two chromosome 13 microRNAs (mir-15a and mir-16-1) were identified. The critical region on zebrafish LG9 maps to the MDR for both human chromosomes, suggesting a common ancestry for the B-CLL tumor suppressor genes. This is further supported by analysis of the chicken genome where the same 5 genes from 13q14 and 11q22-23 (C13orf1, RFP2, FLJ11712, FDX1, ARHGAP20) lie within a 10.04 Mb region on chromosome 1. In addition, TILLING for knock-outs of genes in this region of zebrafish embryos will allow analysis of their in vivo potential for lymphoproliferation and may define prime causative genes for B-CLL within human chromosomes 11q and 13q by reverse genetics. Our study provides an explanation for involvement of both 11q and 13q in B-CLL and the potential to develop animal models for this common lymphoproliferative disorder.


2006 ◽  
Vol 12 (4) ◽  
pp. 187-192
Author(s):  
F. Scamardella ◽  
M. Maconi ◽  
L. Albertazzi ◽  
B. Gamberi ◽  
L. Gugliotta ◽  
...  

Author(s):  
Alessandro Pileri ◽  
Carlotta Baraldi ◽  
Alessandro Broccoli ◽  
Roberto Maglie ◽  
Annalisa Patrizi ◽  
...  

2001 ◽  
Vol 194 (11) ◽  
pp. 1639-1648 ◽  
Author(s):  
Andreas Rosenwald ◽  
Ash A. Alizadeh ◽  
George Widhopf ◽  
Richard Simon ◽  
R. Eric Davis ◽  
...  

The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression “signature,” irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.


2021 ◽  
Author(s):  
Francesca Magrinelli ◽  
Sara Mariotto ◽  
Gianpaolo Nadali ◽  
Giuseppe Todeschini ◽  
Massimiliano Lanzafame ◽  
...  

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