The gene for galactosyltransferase maps to mouse chromosome 4

The chromosomal localization of the gene for UDP-galactosyltransferase (glycoprotein 4-B-galactosyltransferase, EC 2.4.1.38) has been determined to be on mouse chromosome 4 by the use of mouse X hamster somatic cell hybrids. It has been proposed that galactosyltransferase is associated with the mouse T/t complex which has been localized to mouse chromosome 17. These results show that galactosyltransferase is not encoded within the T/t complex.     

The peripherin gene maps to mouse chromosome 15

We have mapped the mouse peripherin gene, Prph, to chromosome 15 by means of Southern analysis of a panel of Chinese hamster/mouse somatic cell hybrids using a rat peripherin cDNA probe. Peripherin is a recently characterized type III intermediate filament expressed in the peripheral and the central nervous system. Although its exact function is not known, peripherin is likely to be involved in the neuronal cytoskeleton, a role it shares with other intermediate filaments, such as the neurofilament proteins. The intermediate filament gene family is believed to have evolved via gene duplication and dispersal throughout the genome; these processes have resulted in clusters of intermediate filament genes on specific chromosomes and conservation of these chromosomal locations among mammalian species.     

A gene for familial juvenile polyposis maps to chromosome 18q21.1.

Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which affected family members develop upper and lower gastrointestinal juvenile polyps and are at increased risk for gastrointestinal cancer. A genetic locus for FJP has not yet been identified by linkage; therefore, the objective of this study was to perform a focused genome screen in a large family segregating FJP. No evidence for linkage was found with markers near MSH2, MLH1, MCC, APC, HMPS, CDKN2A, JP1, PTEN, KRAS2, TP53, or LKB1. Linkage to FJP was established with several markers from chromosome 18q21.1. The maximum LOD score was 5.00, with marker D18S1099 (recombination fraction of .001). Analysis of critical recombinants places the FJP gene in an 11.9-cM interval bounded by D18S1118 and D18S487, a region that also contains the tumor-suppressor genes DCC and DPC4. These data demonstrate localization of a gene for FJP to chromosome 18q21.1 by linkage, and they raise the possibility that either DCC or DPC4 could be responsible for FJP.     

The mouse lysyl oxidase-like 2 gene (mLOXL2) maps to chromosome 14 and is highly expressed in skin, lung and thymus.

The predicted amino acid sequence derived from a mouse expressed sequence tag (EST) contig contained two domains that are highly conserved among members of the lysyl oxidase gene family: a copper binding-site with four histidines and a catalytic domain that includes a tryptophan residue. This new cDNA sequence showed the highest level of sequence homology with the human loxl2 cDNA and suggested that it encoded the mouse equivalent of hLOXL2. The mLOXL2 gene was mapped to chromosome 14 by radiation hybrid analysis. The mLOXL2 locus was tightly linked with a LOD score over 9 to the marker D14Mit32. The mLOXL2 gene is expressed as a 4-kb mRNA in almost all tissues analyzed, with highest levels of mRNA in skin, lung and thymus.     

The gene for cherubism maps to chromosome 4p16.3.

Cherubism is a rare familial disease of childhood characterized by proliferative lesions within the mandible and maxilla that lead to prominence of the lower face and an appearance reminiscent of the cherubs portrayed in Renaissance art. Resolution of these bony abnormalities is often observed after puberty. Many cases are inherited in an autosomal dominant fashion, although several cases without a family history have been reported. Using two families with clinically, radiologically, and/or histologically proved cherubism, we have performed a genomewide linkage search and have localized the gene to chromosome 4p16.3, with a maximum multipoint LOD score of 5. 64. Both families showed evidence of linkage to this locus. Critical meiotic recombinants place the gene in a 3-cM interval between D4S127 and 4p-telomere. Within this region a strong candidate is the gene for fibroblast growth factor receptor 3 (FGFR3); mutations in this gene have been implicated in a diverse set of disorders of bone development.     

The gene for cherubism maps to chromosome 4p16.

Cherubism is an autosomal dominant disorder that may be related to tooth development and eruption. It is a disorder of age-related bone remodeling, mostly limited to the maxilla and the mandible, with loss of bone in the jaws and its replacement with large amounts of fibrous tissue. We have used a genomewide search with a three-generation family and have established linkage to chromosome 4p16. Three other families affected with cherubism were also genotyped and were mapped to the same locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus spans an interval of approximately 22 cM.     

The locus for bovine dilated cardiomyopathy maps to chromosome 18

Bovine dilated cardiomyopathy (BDCMP) is a severe and terminal disease of the heart muscle observed in Holstein-Friesian cattle over the last 30 years. There is strong evidence for an autosomal recessive mode of inheritance for BDCMP. The objective of this study was to genetically map BDCMP, with the ultimate goal of identifying the causative mutation. A whole-genome scan using 199 microsatellite markers and one SNP revealed an assignment of BDCMP to BTA18. Fine-mapping on BTA18 refined the candidate region to the MSBDCMP06-BMS2785 interval. The interval containing the BDCMP locus was confirmed by multipoint linkage analysis using the software loki. The interval is about 6.7 Mb on the bovine genome sequence (Btau 3.1). The corresponding region of HSA19 is very gene-rich and contains roughly 200 genes. Although telomeric of the marker interval, TNNI3 is a possible positional and a functional candidate for BDCMP given its involvement in a human form of dilated cardiomyopathy. Sequence analysis of TNNI3 in cattle revealed no mutation in the coding sequence, but there was a G-to-A transition in intron 6 (AJ842179:c.378+315G>A). The analysis of this SNP using the study's BDCMP pedigree did not conclusively exclude TNNI3 as a candidate gene for BDCMP. Considering the high density of genes on the homologous region of HSA19, further refinement of the interval on BTA18 containing the BDCMP locus is needed.     

Shiverer gene maps near the distal end of chromosome 18 in the house mouse

Several mouse mutations cause unstable locomotion, tremor, seizures, and a reduced lifespan because of deficient myelin formation in the central nervous system. Mutant alleles at the shiverer (shi) locus are the only ones in this series with a selective molecular defect, namely, in myelin basic proteins (MBPs), which are virtually absent in shi homozygotes and 50% reduced in heterozygotes. In the present study, backcross and intercross matings indicate recombination of 21.2 +/- 3.3% between myelin deficient, shimld, and fused phalanges, syfp, a marker near the middle of chromosome 18. Recombination of shimld with twirler (Tw), a marker near the centromere, is 45.7 +/- 4.9%. Thus, the shi locus maps near the distal end of mouse chromosome 18 and is the first available marker for this region. Given the evidence of other workers that an MBP locus maps to the same mouse chromosome, and that part of this chromosome may be syntenic with an MBP-PEPA region on human chromosome 18, it is likely that shi is in or near an MBP gene.     

Molecular cloning of human lysyl oxidase and assignment of the gene to chromosome 5q23.3-31.2.

Lysyl oxidase (EC 1.4.3.13) initiates the crosslinking of collagens and elastin by catalyzing oxidative deamination of the epsilon-amino group in certain lysine and hydroxylysine residues. We report here on the isolation and characterization of cDNA clones for the enzyme from human placenta and rat aorta lambda gt11 cDNA libraries. A cDNA clone for human lysyl oxidase covers all the coding sequences, 230 nucleotides of the 5' and 299 nucleotides, of the 3' untranslated sequences, including a poly(A) tail of 23 nucleotides. This cDNA encodes a polypeptide of 417 amino acid residues, including a signal peptide of 21 amino acids. Sequencing of two rat lysyl oxidase cDNA clones indicated six differences between the present and the previously published sequence for the rat enzyme [Trackman et al. (1990) Biochemistry 29: 4863-4870], resulting in frameshifts in the translated sequence. The human lysyl oxidase sequence was found to be 78% identical to the revised rat sequence at the nucleotide level and 84% identical at the amino acid level, with the degree of identity unevenly distributed between various regions of the coded polypeptide. Northern blot analysis of human skin fibroblasts RNA indicated that the human lysyl oxidase cDNA hybridizes to at least four mRNA species; their sizes are about 5.5, 4.3, 2.4, and 2.0 kb. Analysis of a panel of 25 human x hamster cell hybrids by Southern blotting mapped the human lysyl oxidase gene to chromosome 5, and in situ hybridization mapped it to 5q23.3-31.2.(ABSTRACT TRUNCATED AT 250 WORDS)