Candidate gene isolation and comparative analysis of a commonly deleted segment of 7q22 implicated in myeloid malignancies.
Monosomy 7 and deletion of 7q are recurring abnormalities in malignant myeloid diseases. Here we extensively characterize an approximately 2-Mb commonly deleted segment (CDS) of 7q22 bounded by D7S1503 and D7S1841. Approximately 1.8 Mb of sequence have been generated from this interval, facilitating the construction of a transcript map that includes large numbers of genes and ESTs. The intron/exon organization of seven genes and expression patterns of three genes were determined, and leukemia samples were screened for mutations in five genes. We have used polymorphic markers from this region to examine leukemia cells for allelic loss within 7q22. Finally, we isolated mouse genomic clones orthologous to several of the characterized human genes. Fluorescence in situ hybridization studies using these clones indicate that a region of orthologous synteny lies on proximal mouse chromosome 5. These resources should greatly accelerate the pace of candidate gene discovery in this region.
Kratz
C P
CP
Department of Pediatrics, University of California, San Francisco, California 94143, USA.
Emerling
B M
BM
Donovan
S
S
Laig-Webster
M
M
Taylor
B R
BR
Thompson
P
P
Jensen
S
S
Banerjee
A
A
Bonifas
J
J
Makalowski
W
W
Green
E D
ED
Le Beau
M M
MM
Shannon
K M
KM
D000208:Acute Disease; D000328:Adult; D000818:Animals; D002648:Child; D002872:Chromosome Deletion; D022202:Chromosomes, Artificial, Bacterial; D027042:Chromosomes, Artificial, P1 Bacteriophage; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003001:Cloning, Molecular; D019295:Computational Biology; D020451:Contig Mapping; D005091:Exons; D020224:Expressed Sequence Tags; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009006:Monosomy; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D026801:Synteny