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M F Seldin

Publications and source records attributed to M F Seldin.

At least 217 records · Page 12Linked to original sources

Long-range restriction site mapping of a syntenic segment conserved between human chromosome 1 and mouse chromosome 3.

A linkage map determined from segregation analysis of 338 meiotic events in an interspecific mouse cross was utilized to help investigate genomic organization of a linkage group conserved between human chromosome 1p and mouse chromosome 3. Using pulsed-field gel electrophoresis, the genes encoding the lymphocyte adhesion molecule human CD2/murine Ly-37, the alpha 1-subunit of Na, K-ATPase, the beta-subunit of thyrotropin, the beta-subunit of nerve growth factor, and muscle adenylate deaminase were similarly positioned on long-range restriction maps in both species. These studies indicate that the development of detailed genetic maps using interspecific Mus crosses facilitates rapid analysis of murine genomic organization and may enable physical mapping of syntenic regions within the human genome. Moreover, the data suggest profound conservation of genomic organization during mammalian evolution.

AMP Deaminase↗

The syntenic relationship of proximal mouse chromosome 7 and the myotonic dystrophy gene region on human chromosome 19q.

The syntenic relationship of the myotonic dystrophy (DM) gene region on human chromosome 19q and proximal mouse chromosome 7 was examined using an interspecific backcross between C3H/HeJ-gld/gld mice and Mus spretus. Segregation analyses were used to order homologs of nine human loci linked with the DM gene. Their order from the centromere was Prkcg, [Apoe, Atpa-2, Ckmm, D19S19h, Ercc-2], Cyp2b, Mag, Lhb. Two other murine loci, D7Rp2 and Ngfg, were also positioned within this interval. Homologs for five human chromosome 11 and 15 loci (Calc, Fes, Hras-1, Igflr, Tyr) were localized within an 18-cM span telomeric to Lhb. Comparison of the gene orders indicates an inversion extending from Prkcg through the interval between Mag and Lhb. This study establishes a detailed map of proximal mouse chromosome 7 that will be useful in identifying and determining whether new human chromosome 19 probes are linked to the DM region.

Animals↗

Localization of mouse melanoma growth stimulatory activity gene (Mgsa) between Afp and Gus on chromosome 5 using interspecific backcross mice.

Melanoma growth stimulatory activity (Mgsa) is a polypeptide mitogen and a possible autocrine growth factor for melanoma and other tumor cells. A restriction fragment length variant of Mgsa was followed in interspecific backcross mic Mgsa was localized between Afp and Gus on mouse chromoson 5, distal to known loci affecting skin pigmentation.

Animals↗

A 6000 kb segment of chromosome 1 is conserved in human and mouse.

A murine linkage map generated from analyses of 428 meiotic events in an interspecific cross and pulsed field gel electrophoresis allowed examination of the genomic organization of a 6000 kb segment of mouse and human chromosome 1. Analysis of five genes within this syntenic segment of both species revealed striking conservation of gene order, intergenic distance and, to a lesser extent, CpG dinucleotides. In the mouse, meiotic crossover events were not evenly distributed; a hot spot for meiotic recombination was coincident with a CpG-island. These studies provide a practical approach to aid physical mapping of the human genome and a model for determining the molecular principles that govern meiotic recombination. In addition, these findings demonstrate profound conservation of genomic organization over mammalian evolution.

Animals↗

Molecular analysis of the murine C4b-binding protein gene. Chromosome assignment and partial gene organization.

Murine C4b-binding protein (C4BP) is a regulatory molecule in the classical pathway of complement. C4BP is composed predominantly of short consensus repeats (SCRs) approximately 60 amino acids in length, which contain a framework of conserved residues. The SCRs are found in many complement molecules and a growing number of noncomplement molecules as well and are a major structural feature of some of these molecules. To characterize the structure of the murine C4BP gene, a cosmid library constructed from Balb/c liver DNA was screened. Several nearly identical, overlapping clones were identified; however, none of the clones, alone or in combination, covered the entire C4BP gene. One clone (D26) was chosen for detailed analysis and found to contain all but the leader region, the first SCR, and the first half of the second SCR. The SCRs three through six were each encoded by single exons. Only the latter half of the second SCR was present on the clone, and it was encoded by a single exon, demonstrating that murine C4BP has a split SCR at the genomic level. Structural mapping of this portion of the gene demonstrates that the region extending from the second half of the second SCR through the nonrepeat and untranslated region spans approximately 12 kb; however, genomic Southern blot analysis suggests that the gene is between 20 and 30 kb in length. Analysis of the 3' genomic sequence demonstrates that this region of the gene has homology with SV-40 late (class II) RNA sequences. These sequences may play a role in 3' cleavage of the precursor RNA prior to polyadenylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

The isolation and characterization of the murine T cell antigen receptor zeta chain gene.

The T cell antigen receptor (TCR) is a multisubunit complex which has a dual function of antigen recognition and signal transduction. One of its invariant subunits, the zeta chain, has been shown to have a significant role in the expression and function of the TCR on the cell surface. The mouse and human zeta cDNAs share significant homologies to each other but are distinct from all of the previously characterized TCR components. We now report the isolation and structural analysis of the complete murine zeta gene. This gene spans at least 31 kilobases and divides into eight exons. The first exon, which is located at least 20 kilobases upstream from the second exon, codes for the 5'-untranslated region and most of the signal peptide. The second exon codes for the remainder of the signal peptide, the extracellular domain, the transmembrane domain, and the first three amino acids of the intracytoplasmic domain. Exons 3-7 encode the majority of the intracytoplasmic domain. The eight exon encodes the carboxyl-terminal 21 amino acids and the 3'-untranslated region. Four groups of mRNA initiation sites have been identified at approximately 140 base pairs upstream to the AUG codon. No TATA-like box has been detected. The gene is localized to the distal part of chromosome 1 in a linkage group highly conserved between man and mouse.

Animals↗

Genetic organization of complement receptor-related genes in the mouse.

Using an interspecific cross, gene linkage relationships among members of the murine complement receptor-related genes, C4bp, Cfh, Mcry, and Mcr2, were analyzed by segregation of RFLP in 200 mice. The human homologues of these genes are tightly linked, composing the RCA locus, which maps to human chromosome (Chr.)1q32, within a large linkage group conserved between human Chr.1q21-32 and mouse Chr.1. RFLP associated with C4bp and Cfh map within this conserved linkage group; Cfh is located 9 cM telomeric to C4bp, which is consistent with linkage data for their human homologues. Mcry and Mcr2, while tightly linked, are located outside the conserved group, 40 cM telomeric to C4bp. These data suggest that a translocation or inversion occurred within the RCA family during the evolution of the mouse, defining a breakpoint of this large conserved linkage group.

Animals↗

Physical mapping of a family of interferon-activated genes, serum amyloid P-component, and alpha-spectrin on mouse chromosome 1.

This report defines genetic and physical relationships among alpha-spectrin (Spna-1), serum amyloid P-component (Sap), and a family of interferon-activated genes, provisionally designated Ifi202, Ifi203, and Ifi204. By linkage analysis using a large panel of interspecific backcross mice, Sap, Ifi202, and Ifi204 were shown to be tightly linked to Spna-1 on distal mouse chromosome 1. By pulsed field electrophoresis, a genomic restriction map of 6400 kb of distal mouse chromosome 1 was generated, linking genes encoding Sap, (Ifi202, Ifi203, Ifi204), and Spna-1 in that order within 450-1000 kb (where the genes within brackets were not ordered). The interferon-activated genes Ifi202, Ifi203, and Ifi204 were linked within 75-150 kb. Furthermore, genes transcriptionally activated by cytokines, namely Sap, Ifi202, Ifi203, and Ifi204, were located within 450 kb. These studies suggest the possibility that selective pressure may maintain in physical proximity gene clusters which are under coordinate transcriptional control.

Animals↗

Interferons as gene activators: a cluster of six interferon-activatable genes is linked to the erythroid alpha-spectrin locus on murine chromosome 1.

Several interferon-activatable murine genes were mapped to murine chromosomes by hybridizing cDNA probes to Southern blots of genomic DNA samples from a panel of mouse-hamster somatic cell hybrid lines. The 12 gene is located on chromosome 12 and it specifies a 3.6-kb mRNA. The 204 gene (specifying a 2.5-kb mRNA), and three genes of the 203 gene family (hybridizing to five mRNAs of sizes between 2 and 4.5 kb), together with the 202 gene (specifying a 2-kb mRNA) are located on murine chromosome 1. By restriction fragment length polymorphism analysis of DNA samples prepared from a panel of recombinant inbred mouse lines (C57BL/6J D DBA/2J) and from 85 [C3H/HeJ-gld/gld x Mus spretus) F1 X C3H/HeJ-gld/gld] backcross mice we established a close linkage of the 202, 203, and 204 genes to the erythroid alpha-spectrin gene (Spna-1) on distal murine chromosome 1. Cosmids containing the 202, 203, and 204 genes were isolated from a library derived from AKR mouse DNA. Southern blot analysis of such cosmids revealed: (a) hybridization of a partial 203 cDNA to three genes of the 203 gene family; (b) cross-hybridization of the 202 and 204 genes with one another and with a third gene (designated as 201 gene), and (c) a close linkage of genes of the 203 family with the 201, 202, and 204 genes. These results indicate the existence of a cluster of at least six closely linked, interferon-activatable genes on distal murine chromosome 1 in the vicinity of the Spna-1 locus and also of the Minor lymphocyte stimulating locus (Mlsa).

Animals↗

A glutaminase (gis) gene maps to mouse chromosome 1, rat chromosome 9, and human chromosome 2.

A rat cDNA clone encoding a portion of phosphate-activated glutaminase was used to identify DNA restriction fragment length polymorphisms (RFLPs) in sets of somatic cell hybrids and between wild-derived and inbred strains of mice. Segregation of rat and mouse chromosomes among somatic cell hybrids indicated assignment to rat chromosome 9 and mouse chromosome 1. Analysis of chromosome 1 alleles for several genes in an interspecific cross between Mus spretus and C3H/HeJ-gld/gld mice indicates that glutaminase can be positioned within 5.5 +/- 2.0 cM proximal to Ctla-4. Similarly, human-hamster somatic cell hybrids were examined for RFLPs, and four human EcoRI restriction fragments were found to hybridize with the rat glutaminase probe. Two of these restriction fragments cosegregated and mapped to human chromosome 2 in a region that is syntenic with mouse chromosome 1 and rat chromosome 9.

Animals↗

Comparison of linkage maps of mouse chromosome 12 derived from laboratory strain intraspecific and Mus spretus interspecific backcrosses.

Progeny from an interspecific backcross between laboratory mice and Mus spretus were typed for inheritance of eight genetic markers on chromosome 12. Marker order determined by segregation analyses of 115 meiotic events was in good agreement with that determined previously using intraspecific laboratory strain backcrosses. Two additional markers, D12Nyu5 and Lamb-1, previously not ordered, were located in the middle of the interval between D12Nyu12 and D12Nyu1. Marker spacing was reduced in the interspecific cross relative to that observed in intraspecific crosses. Furthermore, the interspecific cross was characterized by marked deviation from 1:1 segregation in the recombinant chromosomes and very strong positive interference. These data suggest that comparisons of different mouse crosses may facilitate the understanding of underlying mechanisms that govern recombination events in complex genomes.

Alleles↗

Definition of mouse chromosome 1 and 3 gene linkage groups that are conserved on human chromosome 1: evidence that a conserved linkage group spans the centromere of human chromosome 1.

Comparative mapping between the human and the mouse genomes allows characterization of linkage groups that have been conserved over evolution. In this study, genes previously localized to adjacent regions of human chromosome 1 were mapped to discrete regions on distal mouse chromosomes 1 and 3 using an interspecific cross. Linkage analysis in mouse defined two groups in which the gene order appears to be the same as that in humans: 15 genes localized between human chromosome 1q21 and 1q32 were found to span 29.5 cM on distal mouse chromosome 1; 6 genes localized between human chromosome 1q21 and 1p22 spanned 15.6 cM on distal mouse chromosome 3. These data suggest that gene order within large chromosome segments may remain stable over long periods of evolution and that the position of the centromere may reflect a late event in the evolution of higher eukaryotic organisms. These studies provide a model for examination of specific evolutionary events.

Animals↗

Mapping of Abll within a conserved linkage group on distal mouse chromosome 1 syntenic with human chromosome 1 using an interspecific cross.

A human Abelson related gene (ABLL) cDNA clone was used to detect restriction fragment length polymorphisms (RFLPs) on mouse Southern blots. Abll was mapped to mouse chromosome 1 by analysis of segregation with other distal chromosome 1 genetic polymorphisms by using a panel of DNAs from [(C3H/HeJ-gld/gld x Mus spretus) F1 x C3H/HeJ-gld/gld] interspecific backcross mice. The data indicate the following gene order: (centromere)-CD45-6.5 cM-Lamb-2-1 cM-Abll-2 cM-At-3. The results extend the analysis of a large conserved linkage group spanning nearly 30 cM on distal mouse chromosome 1 syntenic with human chromosome 1q21-32. Within this linkage group similar relative positions have been characterized in both species for C4BP, REN, CD45, LAMB2, ABLL, AT3, APOA2, and SPTA.

Animals↗

Genetic analysis of autoimmune gld mice. I. Identification of a restriction fragment length polymorphism closely linked to the gld mutation within a conserved linkage group.

A linkage map of distal mouse chromosome 1 was generated using restriction fragment length polymorphism (RFLP) analysis of DNA prepared from 95 [C3H-gld/gld X Mus spretus)F1 X C3H-gld/gld] backcross mice. The gene order was: (centromere) C4bp, Ren-1,2, Ly-5, [At-3/gld], Apoa-2/Ly-17, Spna-1 (telomere). All mice expressing the phenotype of gld homozygotes were homozygous for the At-3 RFLP characteristic of C3H mice and none of the mice heterozygous for At-3 RFLPs had characteristics of gld homozygotes, demonstrating close linkage between these genes. The identification of an RFLP closely linked to the gld gene provides a starting point for the identification of a genetic defect that results in abnormal T cells and autoimmune disease.

Animals↗