We have analysed the effect of androgens on the activity of promoters from MMTV, and the rat prostate C3(1) and mouse secretory protease inhibitor genes. MMTV promoter activity was stimulated by testosterone as well as progesterone and dexamethasone but not by oestradiol. Deletion analysis indicated that the three steroids acted through DNA sequences between nucleotides -201 and -69 upstream of the MMTV cap site. In contrast, the promoters for the C3(1) gene and the protease inhibitor gene were unaffected by testosterone in a number of cell types, including prostate cells, despite the fact that the MMTV promoter was stimulated in such cells.

Androgens↗

PubMed1988

Priming semantic relations in patients with Huntington's disease.

To investigate the hypothesis that Huntington's Disease involves a breakdown in the organization of the lexico-semantic representational system, mildly and moderately demented patients with Huntington's Disease and age-matched normal control subjects were given a brief battery of language tests and a semantic priming free association task. Results of the language tests provided suggestive, but confounded, evidence for a semantic deficit in Huntington's Disease. Less equivocal evidence was yielded by results of the priming task, which showed a decline in the effect of association strength of primed stimulus-target word pairs on target hit rates. This finding was interpreted as a disruption in the system of spreading activation in a lexico-semantic network. This breakdown was contrasted with the more severe language deficits found in dementias which are primarily cortical in origin.

Dementia↗

PubMed1988

A primary genetic map of markers of human chromosome 10.

We have constructed a primary genetic map for human chromosome 10 from 13 polymorphic marker systems defining 11 loci, using a new gene mapping algorithm implemented in the computer program GMS. The loci form a continuous genetic map that spans approximately 116 cM in males and 170 cM in females. These loci provide regularly spaced anchor points for linkage studies, except for one interval that is 28 cM in males and 64 cM in females.

Algorithms↗

PubMed1988

A mapped set of DNA markers for human chromosome 15.

A primary genetic linkage map for human chromosome 15 has been constructed from 16 arbitrary DNA markers genotyped in 59 large reference families. The map spans a genetic distance of 146 cM in males and 187 cM in females. The ratio of female/male genetic distance was approximately 2.1 overall within the region of the chromosome covered by our map, but three segments showed a significant male excess in recombination frequency. A subset of seven of the linked markers would be enough to detect linkage of a genetic defect within the mapped region of chromosome 15, if at least 48 phase-known meioses in affected families were available for analysis.

Alleles↗

PubMed1988

Molecular characterization of a spontaneously generated new allele at a VNTR locus: no exchange of flanking DNA sequence.

Variable-number tandem-repeat (VNTR) DNA markers are contributing new power to human genetic studies because their hypervariable nature allows individualization at the DNA level. The practical value of VNTR markers has been well established for genetic linkage mapping, forensic biology, paternity testing, and monitoring of bone marrow transplants. A popular hypothesis attributes generation of variability at VNTR loci to unequal exchange between homologous chromosomes at meiosis. Contrary to the prediction of this hypothesis, we report here the finding that a newly generated VNTR allele is parental for closely spaced flanking markers; the new allele was generated by loss of one repeat unit, without exchange of flanking DNA sequences. These results are consistent with sister chromatid exchange and polymerase slippage or deletion, as well as with some models for gene conversion.

Alleles↗

PubMed1988

A mapped set of genetic markers for human chromosome 9.

A genetic map of markers for human chromosome 9, spanning a genetic distance of 147 cM in males and 231 cM in females, has been constructed from linkage studies with 19 loci in a large panel of reference families. The markers included four classical systems previously assigned to chromosome 9, and restriction fragment length polymorphisms of two cloned genes, ABL oncogene and argininosuccinase synthetase pseudogene 3 (ASSP3). The remaining 13 marker loci, with an average heterozygosity of 42%, were defined by arbitrary DNA probes newly ascertained from genomic libraries; seven of them were variable number of tandem repeat (VNTR) loci. A subset of 7 of the 19 linked markers is proposed for a primary map that could detect linkage with a genetic defect within the covered region of chromosome 9, provided that at least 45 phase-known meioses were available for study in an affected family.

Cell Line↗

PubMed1988

Twelve loci form a continuous linkage map for human chromosome 18.

We have constructed a primary genetic map of human chromosome 18 consisting of 11 DNA markers and one serological marker (JK). Two of these loci define highly polymorphic VNTR systems. The markers define a continuous genetic linkage map of 97 cM in males and 205 cM in females; female genetic distances in a panel of 59 three-generation families were consistently about twice those observed in males. The high odds in support of the linear order of the markers on this recombination map, and the extent of coverage of chromosome 18, indicate that this map will permit efficient linkage studies of human genetic diseases that may be segregating on chromosome 18 and will provide anchor points for development of high-resolution maps for this chromosome.

Alleles↗

PubMed1988

Genotyping and sequence analysis of apolipoprotein E isoforms.

Apolipoprotein E (apoE), a polymorphic plasma protein, is essential for catabolism of lipoproteins by receptor-mediated endocytosis. One of the apoE isoforms (E2) differs in its binding affinity to specific receptors and contributes to variations in lipoprotein metabolism. Diagnosis of apoE isoforms is done by isoelectric focusing, but it is hindered by various degrees of post-translational sialylation of the apoE protein. Electrophoretically silent structural variations may also escape detection by this technique. We describe a method for genotyping apoE based on hybridization of allele-specific oligonucleotides with enzymatically amplified genomic DNA, which permits unambiguous diagnosis of six common apoE phenotypes within 24 h. Among 100 E2 alleles present in 81 unrelated individuals genotyped by this technique, we found two rare structural mutants of apoE in addition to the common E2 form, E2(158Arg----Cys). Automated sequencing of amplified DNA identified the rare mutants as E2(136Arg----Ser) and E2(145Arg----Cys). The genotypic method may complement or even replace isoelectric focusing for routine determination of apoE phenotypes and for identification of rare structural variants.

Alleles↗

PubMed1988

An extended genetic linkage map of markers for human chromosome 10.

We have extended, in both directions, our recently published genetic map of markers for human chromosome 10 by the addition of 10 newly defined arbitrary loci. The map now covers 230 cM in males and 329 cM in females. In addition, three new markers, one of them a new RFLP at the IRBP gene locus, have been mapped in the vicinity of the locus responsible for multiple endocrine neoplasia type 2A (MEN2A). A significantly higher frequency of recombination in males than in females was observed near both ends of the new map.

Chromosome Mapping↗

PubMed1988

A primary map of ten DNA markers and two serological markers for human chromosome 19.

We have constructed a primary map of 10 DNA and 2 protein markers for chromosome 19. Three of the markers define loci with a variable number of tandem repeats (VNTRs); 3 define genes--insulin receptor, low-density lipoprotein (LDL) receptor, and apolipoprotein CII; and 2 are classical markers for blood group antigens (Lewis and Secretor). The estimated genetic distance covered by the map is 137 cM in males and 189 cM in females. In some regions of the chromosome we found significant differences in recombination frequencies according to sex. This set of markers will be efficient for linkage studies in families segregating genetic defects and will provide anchor points for a high-resolution map of chromosome 19.

Alleles↗