So many genes; so little time: A short cut to mapping genes
- Cedars-Sinal Medical Center & UCLA, Los Angeles, CA (United States)
- Institute for Genomic Research, Gaithersburg, MD (United States); and others
DNA sequencing all transcribed DNAs has been successfully adopted worldwide as a strategy for rapidly defining most of the genes in the human genome. The rapid application of these sequences as STSs for genome mapping and as disease markers requires a knowledge of their chromosomal location. Our laboratory has now combined high resolution chromosome banding technology with sensitive fluorescence in situ hybridization to rapidly localize human cDNAs to single bands of metaphase chromosomes with high fidelity. Using these techniques in an multicenter trial, we have determined the accuracy, sensitivity and speed of this approach for genome map construction and tested 250 cDNAs from random sequencing of cDNA libraries constructed from fetal brain, heart, bone marrow, prostate, testis and hydatidiform mole tissues. cDNAs resulting from zinc finger motif analyses have also been analyzed. The results support this approach as a valid strategy for cost-effective, high throughput gene mapping. Over the 160 cDNAs (about 65%) including 60-70 with database matches have been assigned to single human chromosome bands using ISCN nomenclature at a resolution of 2-5 Mb with a chromosomal distribution approximating that in GDB. These include novel protein kinases, DNA binding proteins, novel members of signal transduction pathways, structural proteins, uncloned housekeeping sequences and novel members of the zinc finger family. The validity of this approach is supported by the accurate mapping of more than 30 genes with confirmatory data using other techniques and by the ability to accurately map genes associated with pseudogene families of 93% homology. The rapid mapping of cDNAs provides immediate gene candidates for human and mouse models of disease and an independently mapped array of STSs with which to sort out the conundrums and to orient the backbone YAC map.
- OSTI ID:
- 134425
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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