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Biomedical subjects

G E Herman

Publications and source records attributed to G E Herman.

At least 37 records · Page 2Linked to original sources
PubMed1996

A comparative transcription map of the murine bare patches (Bpa) and striated (Str) critical regions and human Xq28.

The X-linked developmental mouse mutations bare patches (Bpa) and striated (Str) may be homologous to human X-linked dominant chondrodysplasia punctata (CDPX2) and incontinentia pigmenti (IP2), respectively, based on their genetic mapping and clinical phenotypes. Bpa and Str have been localized to an overlapping critical region of 600 kb that demonstrates conserved gene order with loci in human Xq28 between DXS1104 and DXS52. As part of efforts to isolate the genes involved in these disorders, we have begun to develop a comparative transcription map spanning this region in both species. Using techniques of cross-species conservation and hybridization, exon trapping, and cDNA selection we have identified four known genes or members of gene families--caltractin, a member of the gamma-aminobutyric acid (GABAA) receptor gene family, a member of the melanoma antigen gene (MAGE) family, and several members of the murine-specific, X-linked lymphocyte regulated gene (Xlr3) family. Trapped exons and, in some cases, longer cDNAs have been isolated for potentially 7-9 additional genes. One cDNA demonstrates highly significant homology with members of the Krüppel family of zinc finger transcription factors. A second novel cDNA demonstrates homology at the 3' end of the predicted amino acid sequence to a LIM domain consensus. Gene order appears conserved among those cDNAs determined to be present in both human and mouse. Three of the murine transcripts appear to be present in multiple copies within the Bpa/Str critical region and could be associated with a predisposition to genomic rearrangements. Reverse transcriptase PCR (RT-PCR) and Northern analysis demonstrate that several of the transcripts are expressed in mid-gestation murine embryos and neonatal skin, making them candidates for the Bpa and Str mutations and their respective homologous human disorders.

Amino Acid Sequence↗
PubMed1995

Genetic analyses of tattered, an X-linked dominant, developmental mouse mutation.

Tattered (Td) is an X-linked dominant mouse mutation that causes prenatal lethality in affected males. To map the locus, we analyzed 199 normal male and affected female progeny from a backcross of Td and Mus castaneus. Pedigree analysis of these animals suggests a gene order of cen-DXWas70-(Td, DXMit26, Gata1, Tcfe3)-(Cybb, Otc)-tel, where Tcfe3 is a transcription factor homologous to a gene involved in the murine microphthalmia (mi) mutation [Hodgkinson et al. Cell 74, 395-404, 1993]. To evaluate Tcfe3 as a candidate for Td, heterozygous tattered females were crossed to xid males to obtain females in which > 95% of B cells expressed genes solely from the Td X Chromosome (Chr). Fluorescent activated cell sorting (FACS) analysis and Western blotting of isolated splenocytes from Td/xid double heterozygotes rule out Tcfe3 as a likely candidate for the Td mutation.

Animals↗
PubMed1995

Refined mapping of caltractin in human Xq28 and in the homologous region of the mouse X chromosome places the gene within the bare patches (Bpa) and striated (Str) critical regions.

Caltractin belongs to a family of calcium-binding proteins and is a structural component of the centrosome. A human caltractin cDNA (CALT) has recently been mapped by fluorescence in situ hybridization (FISH) to Xq28. We report here refined mapping of the human CALT gene and its murine homolog between the loci DXS1104 (DXHXS1104) DXS52 (DXHXS52) by PCR and Southern analysis on YACs and somatic cell hybrids from the region in both species. These mapping studies place the gene within the critical region for the murine X-linked dominant, male lethal mutations bare batches and striated.

Animals↗
PubMed1994

Comparative mapping of the actin-binding protein 280 genes in human and mouse.

Two genes encode actin-binding protein 280 isoforms. ABP-280 or filamin (FLN1) is present in the cytoskeleton of many cell types, whereas expression of FLN2 is limited to skeletal muscle and heart. FLN1 maps to human chromosome Xq28, and, by physical mapping in YAC clones, we have mapped the homologous murine locus (Fln1) to mouse chromosome X, in a region of syntenic homology with human chromosome X. We mapped FLN2 to human chromosome 7q32-q35 by analysis of somatic cell hybrids containing portions of chromosome 7, and, by using a mapping panel from an interspecific murine cross, we mapped the corresponding murine locus (Fln2) to murine chromosome 6 in a region homologous to human chromosome 7.

Animals↗
PubMed1994

A 2.3-Mb yeast artificial chromosome contig spanning from Gabra3 to G6pd on the mouse X chromosome.

A yeast artificial chromosome (YAC) contig of approximately 2.3 Mb has been constructed for the region of the mouse X chromosome between Gabra3 and G6pd. YACs were isolated from four genomic libraries by PCR or hybridization screening for the loci Gabra3, DXHX1104, F8a, DXHX52, DXBay2, L1cam, and Rsvp. Orientation of YACs was performed by isolation of ends using several PCR-based methods, including an adaptation for mouse YAC analysis of interspersed repetitive sequence (IRS)-vector PCR. YAC ends were mapped on a panel of somatic cell hybrids, in an interspecific backcross, using pulsed-field gel (PFG) electrophoresis or by hybridization to other YACs in the contig. Overlapping YACs were further aligned by restriction mapping using rare-cutter restriction endonucleases, as well as by comparison of IRS-PCR fingerprints. This contig represents the largest one assembled to date in the mouse. It should facilitate the isolation of genes in the region and may aid in the completion of a physical contig for the homologous human region, Xq28.

Animals↗
PubMed1994

Glycogen storage disease in adults.

OBJECTIVE: To identify complications amenable to prevention in adults with glycogen storage disease (GSD) types Ia, Ib, and III and to determine the effect of the disease on social factors. DESIGN: Case series and clinical review. SETTING: Referral medical centers in the United States and Canada. PATIENTS: All patients with GSD-Ia (37 patients), GSD-Ib (5 patients), and GSD-III (9 patients) who were 18 years of age or older. MEASUREMENTS: Ultrasound or radiographic studies identified liver adenomas, nephrocalcinosis, or kidney stones. Radiographic studies identified osteopenia. Reports of the clinical examination, serum chemistry results, and social data were obtained. RESULTS: For patients with GSD-Ia, problems included short stature (90%), hepatomegaly (100%), hepatic adenomas (75%), anemia (81%), proteinuria or microalbuminuria (67%), kidney calcifications (65%), osteopenia or fractures or both (27%), increased alkaline phosphatase (61%) and gamma-glutamyltransferase (93%) activities, and increased serum cholesterol (76%) and triglyceride (100%) levels. Hyperuricemia was frequent (89%). Patients with GSD-Ib had severe recurrent bacterial infections and gingivitis. In patients with GSD-III, 67% (6 of 9) had increased creatinine kinase activity. Four of these patients had myopathy and cardiomyopathy. CONCLUSIONS: For GSD-Ia, hyperuricemia and pyelonephritis should be treated to prevent nephrocalcinosis and additional renal damage. For GSD-Ib, granulocyte-colony-stimulating factor may prevent bacterial infections. For GSD-III, more data are required to determine whether the myopathy and cardiomyopathy can be prevented. Most of the patients with GSD-I and GSD-III had 12 or more years of education and were either currently in school or employed.

Adult↗
PubMed1994

Genetic and physical mapping of a gene encoding a methyl CpG binding protein, Mecp2, to the mouse X chromosome.

The methyl CpG binding proteins (MeCP1 and MeCP2) are a class of proteins that bind to templates containing symmetrically methylated CpGs. Using an interspecific backcross segregating a number of X-linked markers, we have localized the Mecp2 gene in mouse to the X chromosome close to the microsatellite marker DXMit1. Detailed physical mapping utilizing an available YAC contig encompassing the DXMit1 locus has localized the Mecp2 gene to a 40-kb region between the L1cam and the Rsvp loci, indicating the probable position of a homologue on the human X chromosome.

Animals↗
PubMed1994

D-2-hydroxyglutaric aciduria in neonate with seizures and CNS dysfunction.

D-2-Hydroxyglutaric aciduria was documented in a newborn who presented with seizures, hypotonia, cortical blindness, a movement disorder, and developmental delay. Her clinical presentation differs from that of patients with L-2-hydroxyglutaric aciduria and a single previously reported patient with D-2-hydroxyglutaric aciduria. Cerebrospinal fluid levels of gamma-aminobutyric acid were elevated, while biogenic amine metabolites were normal. The movement disorder in our patient and in those with L-2-hydroxyglutaric aciduria suggests involvement of the basal ganglia in the disease process. Prenatal diagnosis of an affected fetus was accomplished during a subsequent pregnancy.

Basal Ganglia Diseases↗
PubMed1994

A YAC clone map spanning 7.5 megabases of human chromosome band Xq28.

Xq28 has been of special interest in human genetics because a large number of diseases map to this region. As a step in the molecular analysis of the as yet uncloned disease genes, and as a test for the detailed analysis of larger regions of the genome, we have constructed YAC clone contigs covering the 7.5 Mb region between IDS to the telomere on the long arm of the human X chromosome. Contigs were assembled and verified by an integrated hybridization-based strategy. Data was combined from the physical map, from YAC and cosmid mapping experiments, and from the localization of specific transcripts in the region. Two gaps in the YAC map of 250 and 100 kb were covered in part by the aid of cosmid clones, but small gaps of 50 kb each remain. The cloned region is expected to contain yet unidentified genes for at least ten genetic diseases. The construction of ordered YAC clone contigs of Xq28 represents an important step in the molecular identification of these genes, and the further analysis of one of the genetically most interesting regions of the human genome.

Chromosomes, Artificial, Yeast↗
PubMed1993

Comparative mapping on the mouse and human X chromosomes of a human cDNA clone encoding the vasopressin renal-type receptor (AVP2R).

Mutations in the gene for the human renal-type vasopressin receptor (V2R) have recently been identified in patients with nephrogenic diabetes insipidus (NDI). Both V2R and NDI have been independently mapped to Xq28. Using a combination of genetic and physical mapping, we have localized the murine V2r locus to within 100 kb of L1Cam on the mouse X chromosome in a region syntenic with human Xq28. Based on conserved gene order of mouse and human loci in this region, physical mapping using DNA derived from human lymphoblasts has established that the corresponding human loci V2R and L1CAM are linked within 210 kb. The efficiency and precision of genetic mapping of V2r and other loci in the mouse suggest that it might be easier to map additional human genes in the mouse first and infer the corresponding human location. More precise physical mapping in man could then be performed using pulsed-field gel electrophoresis and/or yeast artificial chromosomes.

Animals↗
PubMed1993

Cloning and characterization of the cDNA for the murine iduronate sulfatase gene.

Iduronate sulfatase (IDS; EC 3.1.6.13) is a lysosomal enzyme that acts on sulfate groups on C-2 positions of iduronic acid residues of the mucopolysaccharides dermatan and heparan sulfate. A deficiency of this enzyme activity in man leads to Hunter syndrome (Mucopolysaccharidosis type II). We report here the cloning and sequence characterization of the murine iduronate sulfatase cDNA which encodes 564 amino acid residues. Within the coding region the murine gene is 84.9 and 84.5 identical to the human gene at the nucleotide and amino acid levels, respectively. The two regions containing the putative catalytic site are especially well conserved. Genetic mapping of the murine Ids cDNA in an interspecific backcross confirms an X chromosomal location between Fmr-1 and Gabra3.

Amino Acid Sequence↗
PubMed1993

Genetic mapping of the X-linked dominant mutations striated (Str) and bare patches (Bpa) to a 600-kb region of the mouse X chromosome: implications for mapping human disorders in Xq28.

Striated (Str) and bare patches (Bpa) are X-irradiation-induced, X-linked dominant mouse mutations that are lethal prenatally in hemizygous males. To map the Str mutation, we generated a backcross involving Mus castaneus. Pedigree analysis of 193 affected female and normal male progeny from the cross places Str extremely close to DXMIT1 and favors a gene order of (Cf-9)-Ids-Gabra3-DXS1104h-(Str, DXMIT1)-F8a-DXPas8-DXBay6-DXMIT6 for the loci studied. This region of the mouse X Chromosome (Chr) is syntenic with proximal human Xq28. Based on the mode of inheritance and clinical phenotype, Str may be a homolog of human familial incontinentia pigmenti (IP2). Further refinement of our genetic mapping of bare patches positions that locus between DXS1104h and DXPas8 in the same region as Str, raising the possibility that Bpa and Str may be allelic or are due to mutations in overlapping contiguous genes.

Animals↗