Novel genes mapping to the critical region of the 5q- syndrome.
The 5q- syndrome is a myelodysplastic syndrome with specific hematological features and a good prognosis. Using molecular mapping techniques, we have previously defined the critical region of gene loss of the 5q- chromosome in the 5q- syndrome as the approximately 5-Mb region at 5q31-q33 flanked by the genes for FGF1 and IL12B. This region is completely represented by a series of overlapping YACs, and we are currently generating a transcription map with the aim of identifying the tumor-suppressor gene associated with the development of the 5q- syndrome. In this study two techniques have been used: first, the screening of full-length cDNA libraries with radiolabeled YACs and second, the mapping of chromosome 5-specific expressed sequence tags (ESTs) to a YAC contig. A 1-Mb YAC contig encompassing the CSF1R gene has been used to screen a fetal brain cDNA library, and this has resulted in the identification of two genes comprising one known gene previously localized to the region (ADRB2) and one known gene previously unlocalized. Six of 135 chromosome 5-specific ESTs were localized by PCR screening to the YAC contig mapping to the critical region of the 5q- syndrome. IMAGE cDNA clones for each of the six ESTs have been obtained. These seven (excluding ADRB2) newly assigned cDNA clones were subjected to further analysis. The expression patterns of each of the cDNA clones have been established in a range of human tissues, including bone marrow. Six of seven cDNAs are expressed in human bone marrow. Six of seven cDNAs have no known homology to any deposited human sequences, and one (C29) is dihydropyrimidinase-related protein-3, a member of a novel gene family. Genomic localization and expression patterns would suggest that these newly assigned cDNAs represent potential candidate genes for the 5q- syndrome.
Boultwood
J
J
Leukaemia Research Fund Molecular Haematology Unit, University Department of Cellular Science, John Radcliffe Hospital, Oxford, United Kingdom.
Fidler
C
C
Soularue
P
P
Strickson
A J
AJ
Kostrzewa
M
M
Jaju
R J
RJ
Cotter
F E
FE
Fairweather
N
N
Monaco
A P
AP
Müller
U
U
Lovett
M
M
Jabs
E W
EW
Auffray
C
C
Wainscoat
J S
JS
D002872:Chromosome Deletion; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002895:Chromosomes, Human, Pair 5; D018076:DNA, Complementary; D018628:Gene Dosage; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D016324:Sequence Tagged Sites
D018076:DNA, Complementary