Integrated mapping analysis of the Werner syndrome region of chromosome 8

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · Genomics

DOI:https://doi.org/10.1006/geno.1994.1464· OSTI ID:186059

Oshima, Junko; Edelhoff, S; Martin, G M ^[1]

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1. Univ. of Washington, Seattle, WA (United States); and others

The Werner syndrome locus (WRN) is located at 8p11-p12. To facilitate eventual cloning of the WRN gene, a 10,000-rad radiation-reduced hybrid (RH) cell panel was generated to map genetic markers, sequence-tagged sites (STSs), and genes in this region. A hamster cell line carrying an intact human chromosome 8 was fused with another hamster cell line. Two sets of hybrid cell panels from 2 separate fusions were generated; each panel consisted of 50 independent clones; 33 and 34 cell lines from the 2 fusions retained human chromosome material as determined by inter-Alu PCR. The combined panel was genotyped for 52 markers spanning the entire chromosome, including 10 genes, 29 anonymous polymorphic loci, and 13 STSs. Seventeen of these markers have not been previously described. Markers near the centromere were retained at a higher frequency than more distal markers. Fluorescence in situ hybridization was also used to localize and order a subset of the markers. An RH map of the WRN region was constructed using a maximum likelihood method, giving the following most likely order: D8S131 - D8S339(GSR) - D8S124 - D8S278 - D8S259 - (D8S71) - D8S283 - D8S87 - D8S105 - D8S135(FGFR1) - D8S135PB - D8S255 - ANK1. A genetic map of 15 short tandem repeat polymorphic loci in the WRN region was also constructed. The marker orders from the genetic and RH maps were consistent. In addition, an integrated map of 24 loci in the WRN region was generated using information from both genetic and RH mapping methods. A 1000:1 framework map for 6 loci (LPL-D8S136-D8S137-D8S87-FGFR1-ANK1) was determined by genetic mapping, and the resulting locus order was fixed during analysis of the RH genotype data. The resulting integrated map contained more markers than could confidently be ordered by either genetic or RH mapping alone. 64 refs., 5 figs., 6 tab.

• OSTI ID: 186059
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 1 Vol. 23; ISSN 0888-7543; ISSN GNMCEP
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AGE DEPENDENCE
ANIMAL CELLS
BIOLOGICAL MARKERS
CENTROMERES
DNA HYBRIDIZATION
DNA-CLONING
ETIOLOGY
FLUORESCENCE
GENE MUTATIONS
GENES
GENETIC MAPPING
GENOTYPE
HAMSTERS
HEREDITARY DISEASES
HUMAN CHROMOSOME 8
HYBRIDIZATION
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
RADIATION INDUCED MUTANTS
RECESSIVE MUTATIONS
STATISTICS