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H M Albertsen

Publications and source records attributed to H M Albertsen.

7 recordsLinked to original sources

Sequence, genomic structure, and chromosomal assignment of human DOC-2.

DOC-2 is a human gene originally identified as a 767-bp cDNA fragment isolated from normal ovarian epithelial cells by differential display against ovarian carcinoma cells. We have now determined the complete cDNA sequence of the 3.2-kb DOC-2 transcript and localized the gene to chromosome 5. A 12.5-kb genomic fragment at the 5'-end of DOC-2 has also been sequenced, revealing the intron-exon structure of the first eight exons (788 bases) of the DOC-2 gene. Translation of the DOC-2 cDNA predicts a hydrophobic protein of 770 amino acid residues with a molecular weight of 82.5 kDa. Comparison of the DNA and amino acid sequences of DOC-2 to publicly accessible sequence databases revealed 83% identify to p96, a murine protein of similar size, thought to be a mitogen-responsive phosphoprotein. In addition, about 45% identity was observed between the first 140 N-terminal residues of DOC-2 and the Caenorhabditas elegans M110.5 and Drosophila melanogaster Dab genes.

Adaptor Proteins, Signal Transducing↗

Loss of chromosome 17 loci in prostate cancer detected by polymerase chain reaction quantitation of allelic markers.

Using a polymerase chain reaction/microsatellite marker system, we demonstrated that 6 of 22 (27%) clinical stage B (early) primary prostate tumors showed loss of heterozygosity at one or more of five loci on chromosome 17. The sensitivity of this study was increased by use of a PhosphorImager and statistical analysis of replicate tumor-normal DNA pairs. Two patients showed tumor-specific interstitial loss at a locus in close proximity to the familial breast cancer gene BRCA1. These findings suggest that genes on the proximal long arm of chromosome 17 play a pivotal role in the early development of at least a subset of prostatic tumors.

Alleles↗

A physical map and candidate genes in the BRCA1 region on chromosome 17q12-21.

We have constructed a physical map of a 4 cM region on chromosome 17q12-21 that contains the hereditary breast and ovarian cancer gene BRCA1. The map comprises a contig of 137 overlapping yeast artificial chromosomes and P1 clones, onto which we have placed 112 PCR markers. We have localized more than 20 genes on this map, ten of which had not been mapped to the region previously, and have isolated 30 cDNA clones representing partial sequences of as yet unidentified genes. Two genes that lie within a narrow region defined by meiotic breakpoints in BRCA1 patients have been sequenced in breast cancer patients without revealing any deleterious mutations. These new reagents should facilitate the identification of BRCA1.

Autoantigens↗

Genetic mapping of 12 marker loci in the Xp22.3-p21.2 region.

To provide a more precise genetic map of the p22.3-p21.2 region on the short arm of the human X chromosome, we performed multilocus linkage studies in an expanded database including 31 retinoschisis families and 40 normal families. Twelve loci from this region were examined. Although significant lod scores were observed between various pairs of markers by two-point linkage analysis, the confidence limits were found to be broad. The most likely gene order on the basis of multilocus analysis was Xpter-DXS89-DXS85-DXS16-(DXS207,DXS43++ +)-DXS274-(DXS41, DXS92)-ZFX-DXS164-Xcen. All other alternative orders were excluded by odds of at least 40:1.

Chromosome Mapping↗

Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents.

Prior to constructing a library of yeast artificial chromosomes (YACs) containing very large human DNA fragments, we performed a series of preliminary experiments aimed at developing a suitable protocol. We found an inverse relationship between YAC insert size and transformation efficiency. Evidence of occasional rearrangement within YAC inserts was found resulting in clonally stable internal deletions or clonally unstable size variations. A protocol was developed for preparative electrophoretic enrichment of high molecular mass human DNA fragments from partial restriction digests and ligation with the YAC vector in agarose. A YAC library has been constructed from large fragments of DNA from an Epstein-Barr virus-transformed human lymphoblastoid cell line. The library presently contains 50,000 clones, 95% of which are greater than 250 kilobase pairs in size. The mean YAC size of the library, calculated from 132 randomly isolated clones, is 430 kilobase pairs. The library thus contains the equivalent of approximately seven haploid human genomes.

Cloning, Molecular↗