Mapping of the human 60 000 M r Ro/SSA locus: the genes for three Ro/SSA autoantigens are located on separate chromosomes

Correspondence to: B. Frank.     

Molecular aspects of sex determination in mice: an alternative model for the origin of the Sxr region

Using a combination of in situ mapping and DNA analysis with recombinant DNA probes specific for the Sxr region of the mouse Y chromosome, we show that both the gene(s) controlling primary sex determination and the expression of the male-specific antigen H-Y (Tdy and Hya respectively) are located on the minute short arm of the mouse Y chromosome. We demonstrate that the H-Y- variant of Sxr (Sxr') arose by a partial deletion within the Sxr region and propose an alternative model for the generation of the original Sxr region.     

Molecular cloning and chromosomal localization of a human peripheral-type benzodiazepine receptor.

The sequencing of endopeptidase-generated peptides from the peripheral binding site (PBS) for benzodiazepines, purified from a Chinese hamster ovary (CHO) cell line, produced internal sequence information, and confirmed and extended the NH2-terminal PBS sequence that we previously reported. Since the sequences were highly similar to the corresponding rat PBS sequences, we investigated whether they were also conserved in human PBS. Scatchard analysis of [3H]PK11195 (a derivative of isoquinoline carboxamide) binding and photoaffinity labeling with [3H]PK14105 (a nitrophenyl derivative of PK11195) revealed that CHO PBS and human PBS are closely related. Furthermore a rabbit antiserum raised against three peptides synthesized on the basis of the CHO PBS sequence immunoprecipitate the solubilized U937 PBS and also recognize the human protein in an immunoblot analysis. Based on these results, we screened a U937 cell cDNA library with four oligonucleotide probes derived from the CHO sequence. Two of the probes hybridized with several clones that we isolated and sequenced. One of these, h-pPBS11, is 831 nucleotides and contains a full-length representation of human PBS mRNA. The amino acid sequence of human PBS deduced from the cDNA is 79% identical to that reported for rat PBS, however, human PBS contains two cysteines while rat PBS is characterized by the absence of this amino acid. Using the cDNA of human PBS as a probe, the PBS gene was located in the 22q13.3 band of the human genome.     

Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome

A mouse cDNA probe homologous to the human MCF2 transforming sequence has been identified and partially cloned, and is used here to localize the gene on the mouse X chromosome. The human gene has been physically mapped to within 60 kb of the gene for coagulation factor IX, within a large conserved linkage group between the mouse and human genomes which extends from HPRT to G6PD on the X chromosomes of both mammalian species. In situ hybridization of the mouse Mcf-2 probe onto mouse metaphase chromosomes indicates that this gene lies in the same region of the X chromosome as Cf-9, the mouse gene for coagulation factor IX. Moreover, segregation of species-specific genomic DNA polymorphisms for Mcf-2 and Cf-9 in a total of 203 individuals derived from two large interspecific mouse backcross populations (which are also segregating for 17 other X-linked molecular markers) demonstrates that the mouse genes are separated by only 0.5 +/- 0.5 cM. Despite this short distance we were able to order Mcf-2 and Cf-9 relative to one another and other genes in this region. The mouse gene order Hprt-Cf-9-Mcf-2-G6pd predicts a similar ordering of genes on the human X chromosome, a gene order which has only recently been demonstrated by physical mapping. Thus, the map location and linkage relationships of the Mcf-2 gene are similar in man and mouse, and this unique protooncogenic locus is part of a conserved linkage group on the mammalian X chromosome.     

Fine mapping of the long arm of human chromosome 11 by in situ hybridization using different translocations, including the t(11;22) of Ewing sarcoma

The progesterone receptor gene (PGR), the gene coding for porphobilinogen deaminase (PBGD), the gene coding for a neural cell adhesion molecule (NCAM), the oncogene ETS1, and the anonymous genomic sequence D11S29 have been previously located on the long arm of chromosome 11. However, gene localizations obtained with different gene-mapping procedures have led to occasional discrepancies. To localize these genes more precisely, we hybridized five human DNA sequences with different chromosomal rearrangements, including four balanced and one unbalanced translocations. We show here that the order of these five sequences is cen-PGR-PBGD-DIIS29/NCAM/ETS1-tel.