Genomic organization and chromosome location of the murine Rpl23 gene

The mouse gene coding for ribosomal protein L23 (Rpl23) has been fully sequenced, including 580 bp of the 5' upstream region. The 5-kb gene comprises 5 exons and contains an unusually long (3,153 bp) third intron. The gene was mapped to the distal region of mouse chromosome 11, homologous to human chromosome 17q21-->q22.     

DNA length polymorphism located 5'' to the human myelin basic protein gene.

A region of DNA 5' to the human myelin basic protein (MBP) gene, located on the long arm of chromosome 18, is a site of restriction-fragment-length polymorphism (RFLP) showing 37% heterozygosity in 40 subjects studied. Southern transfer analysis using a 0.9-kb genomic fragment encompassing the first exon of the human MBP gene reveals this polymorphism with at least nine restriction enzymes, indicating that insertion, deletion, or both is the basis for the DNA length variation. Double restriction-enzyme digest analysis suggests that this polymorphism is within the region 0.5-2.0 kb upstream of the coding region of the first exon of the human MBP gene. Eleven different allelic RFLPs were identified, differing in size by as many as 450 bp. The distribution of insertion/deletion-size variants from this region is bimodal, with most restriction fragments varying in size over a 0.1-kb range. Pedigree analysis of polymorphism at this site in one three-generation family shows Mendelian assortment of parental haplotypes. The form and frequency of polymorphism generated by this site is similar to that reported for human DNA regions comprised of homologous short tandem repeats.     

Structure of the murine mb-1 gene encoding a putative sIgM-associated molecule

Genomic DNA clones containing the B cell-specific murine mb-1 gene were isolated and a 5.6-kb BamH I fragment was characterized. It is 5629 bp long and contains five exons: an exon containing the 5' untranslated and the coding sequence of the signal peptide, an exon of 294 bp, which contains most of the extracellular sequence of the MB-1 protein, a 119-bp long exon coding mainly for the transmembrane portion, and two exons of 69 bp and 427 bp encoding the cytoplasmic domain and the 3'-untranslated region, respectively. The mb-1 gene does not contain a "TATA box" found in many eukaryotic promoters. The 5'-flanking region has sequence stretches homologous to IgVH 5'-promoter regions and a bcl 2 intron sequence. It contains the decanucleotide sequence (ATGGCAAATA) almost identical to the octamer motif of IgVH promoters. A B cell-specific DNase I-hypersensitive site was found in the 3'-flanking region indicating that this region might be involved in B cell-specific expression of mb-1. Southern blot analysis of genomic liver DNA with the cloned mb-1 cDNA suggests the existence of another mb-1-related gene segment.     

Identification of a putative gamma-aminobutyric acid (GABA) receptor subunit rho2 cDNA and colocalization of the genes encoding rho2 (GABRR2) and rho1 (GABRR1) to human chromosome 6q14-q21 and mouse chromosome 4.

Screening of a genomic DNA library with a portion of the cDNA encoding the gamma-aminobutyric acid (GABA) receptor subunit rho1 identified two distinct clones. DNA sequencing revealed that one clone contained a single exon from the rho1 gene (GABBR1) while the second clone encompassed an exon with 96% identity to the rho1 gene. Screening of a human retina cDNA library with oligonucleotides specific for the exon in the second clone identified a 3-kb cDNA with an open reading frame of 1395 bp. The predicted amino acid sequence of this cDNA demonstrates 30 to 38% similarity to alpha, beta, gamma, and delta GABA receptor subunits and 74% similarity to the GABA rho1 subunit suggesting that the newly isolated cDNA encodes a new member of the rho subunit family, tentatively named GABA rho2. Polymerase chain reaction (PCR) amplification of rho1 and rho2 gene sequences from DNA of three somatic cell hybrid panels maps both genes to human chromosome 6, bands q14 to q21. Tight linkage was also demonstrated between restriction fragment length variants (RFLVs) from each rho gene and the Tsha locus on mouse chromosome 4, which is homologous to the CGA locus on human chromosome 6q12-q21. These two lines of evidence confirm that GABRR1 and newly identified GABRR2 map to the same region on human chromosome 6. This close physical association and high degree of sequence similarity raises the possibility that one rho gene arose from the other by duplication.     

Organization and conservation of the GART/SON/DONSON locus in mouse and human genomes

The SON gene, which maps to human chromosome 21q22.1-q22.2, encodes a novel regulatory protein. Here we describe the organization of the Son locus in the mouse genome. The mouse Son gene spans a region of approximately 35 kb. The coding region is more than 8 kb in length and has been completely sequenced. The gene is organized into 11 coding exons and 1 noncoding 3'UTR exon, with over 70% of the coding region residing in one 5.7-kb exon. The gene contains at least one alternative exon, N/C exon 1, which can be used, by splicing, to generate a truncated form of the SON protein. Further investigation of the mouse Son locus has identified the genes directly flanking Son. The glycinamide ribonucleotide formyltransferase gene, Gart, is encoded 5' of Son in a head-to-head arrangement, with the start of both genes lying within 899 bp. Sequence comparison with the expressed sequence tagged database identified a novel gene within 65 bp of the 3' end of Son, which we have named Donson. In this unusually compact gene cluster, we have found overlap in the pattern of expression between Gart, Son, and Donson. However, at least two of these genes have very different functions. While GART is involved in purine biosynthesis, we find that SON shows the characteristics of "SR- type" proteins, which are involved in mRNA processing and gene expression.