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Biomedical subjects

M A Walter

Publications and source records attributed to M A Walter.

At least 55 records · Page 3Linked to original sources
PubMed1996

SOX genes: architects of development.

Development in higher organisms involves complex genetic regulation at the molecular level. The emerging picture of development control includes several families of master regulatory genes which can affect the expression of down-stream target genes in developmental cascade pathways. One new family of such development regulators is the SOX gene family. The SOX genes are named for a shared motif called the SRY box a region homologous to the DNA-binding domain of SRY, the mammalian sex determining gene. Like SRY, SOX genes play important roles in chordate development. At least a dozen human SOX genes have been identified and partially characterized (Tables 1 and 2). Mutations in SOX9 have recently been linked to campomelic dysplasia and autosomal sex reversal, and other SOX genes may also be associated with human disease.

Amino Acid Sequence↗
PubMed1996

Autosomal dominant iridogoniodysgenesis anomaly maps to 6p25.

Autosomal dominant iridogoniodysgenesis anomaly (IGDA) is characterized by iris hypoplasia and goniodysgenesis with frequent juvenile glaucoma. IGDA is the result of aberrant migration or terminal induction of the neural crest cells involved in the formation of the anterior chamber of the eye. After eliminating candidate regions for other ocular disorders, a genome-wide scan for IGDA was performed using linkage analysis. Approximately 95% of the genome was excluded with >300 microsatellite markers before significant linkage was demonstrated between IGDA and chromosome 6 markers in two families. From haplotype analysis and identification of recombinants, the IGDA locus is mapped to an 8.3-cM interval distal to D6S477, at 6p25. Our linkage results are consistent with the ocular findings in rare cases of individuals with chromosomal anomalies involving deletions of 6p. This suggests that there is a major gene involved in eye anterior segment development at 6p25.

Chromosome Mapping↗
PubMed1995

Irradiation and fusion gene transfer.

Irradiation and fusion gene transfer (IFGT) is a technique that spans the gap between the limitations of molecular methods and somatic-cell genetics, allowing the separation of DNA fragments between 0.25 and 30 Mb in size. In conjunction with genetic linkage analysis and physical mapping techniques, IFGT provides a very useful addition to methods for cloning disease loci, and mapping chromosomes and entire genomes.

Animals↗
PubMed1995

Mutation of the PAX6 gene in patients with autosomal dominant keratitis.

Autosomal dominant keratitis (ADK) is an eye disorder chiefly characterized by corneal opacification and vascularization and by foveal hypoplasia. Aniridia (shown recently to result from mutations in the PAX6 gene) has overlapping clinical findings and a similar pattern of inheritance with ADK. On the basis of these similarities, we used a candidate-gene approach to investigate whether mutations in the PAX6 gene also result in ADK. Significant linkage was found between two polymorphic loci in the PAX6 region and ADK in a family with 15 affected members in four generations (peak LOD score = 4.45; theta = .00 with D11S914), consistent with PAX6 mutations being responsible for ADK. SSCP analysis and direct sequencing revealed a mutation in the PAX6 exon 11 splice-acceptor site. The predicted consequent incorrect splicing results in truncation of the PAX6 proline-serine-threonine activation domain. The SeyNeu mouse results from a mutation in the Pax-6 exon 10 splice-donor site that produces a PAX6 protein truncated from the same point as occurs in our family with ADK. Therefore, the SeyNeu mouse is an excellent animal model of ADK. The finding that mutations in PAX6 underlie ADK, along with a recent report that mutations in PAX6 also underlie Peters anomaly, implicates PAX6 broadly in human anterior segment malformations.

DNA-Binding Proteins↗
PubMed1994

The immunoglobulin heavy chain and disease association: application to pemphigus vulgaris.

Genes involved in the immune response are generally encoded from a complex cluster of gene segments. Studies of the association of diseases with such genes require well-defined genetic markers throughout the selected region. A set of 15 polymorphic loci that span 1500 kb of the immunoglobulin heavy chain (IGH) complex, 8 in the variable (VH) region and 7 in the constant (CH) region, were selected for the study of disease association. We present a protocol for the use of multiple immunoglobulin heavy chain (IGH) polymorphisms for general application in disease association studies. No microsatellite repeat markers are available for this region. To demonstrate the applicability of this approach, we have examined these IGH polymorphisms in families with individuals affected with pemphigus vulgaris (PV), an autoimmune dermatologic disease. Allele frequencies in 12 patients with PV were compared with those found in their spouses, and with those in a white Canadian control population. A significant difference was found between PV patients and both control groups for the presence of the VH gene VH3f-R4, and possibly for the absence of VH3f-R3, suggesting the possibility of susceptibility factors in these regions. Examination of the frequencies of the IGH region C gamma-haplotypes of PV patients indicated that, while the patients did not differ significantly from their spouses (chi 2 = 1.79), both groups were found to differ significantly from the white Canadian control group (chi 2 = 10.10), emphasizing the importance of matching the ethnic background of controls with that of the patient test group in disease association studies. Unexpectedly, two patients had large deletions of genes in the IGH constant region, which could play a role in the development of PV and require further investigation.

Alleles↗
PubMed1994

A method for constructing radiation hybrid maps of whole genomes.

In radiation hybrid mapping, chromosomes in human-rodent hybrid cells are fragmented by X-rays and fragments rescued by fusion of the donor cell to a recipient rodent cell. The co-retention frequencies of markers in 100-200 hybrids are used to map individual chromosomes, but mapping the whole genome in this way is impractical. We have reverted to the original protocols of Goss and Harris and have produced a panel of 44 hybrids using irradiated human fibroblasts as donors. This panel has been used to make a map of human chromosome 14 containing 40 ordered markers. The map integrates previously published maps and localizes nine new markers. We suggest that the construction of a high resolution map of the whole human genome is feasible with a single panel of 100-200 hybrids.

Animals↗
PubMed1993

Immunoglobulin heavy chain variable region polymorphisms and multiple sclerosis susceptibility.

In addition to the major histocompatibility complex (MHC), genetic susceptibility in multiple sclerosis (MS) appears to be influenced by other loci. A recent study has identified a population association with an immunoglobulin heavy chain variable region polymorphism in the VH2-B5 family, with both familial and sporadic MS patients. We have repeated this association study in a second MS patient group and used two ethnically and geographically matched control groups and the MS patients' unaffected sibs for comparisons. The VH2-B5 polymorphism was found to be over-represented in MS patients when compared to all three control groups. This VH2-B5 association was stronger when the MS patient data were combined with data from our previous study. To further explore the implications of this population association, MS sibships were analyzed for haplotype sharing by identity by descent (IBD) for VH2 and VH3f gene segment polymorphisms. The distribution of haplotype sharing did not differ from that expected based upon random segregation. The data are consistent with the IGVH locus exerting a minor effect perhaps by interacting with other loci to influence MS susceptibility or with genetic heterogeneity and a role for this complex in a subgroup of patients.

Alleles↗
PubMed1993

Enhanced peripheral nerve regeneration by acidic fibroblast growth factor.

Transection of peripheral nerves may cause permanent denervation with paralysis and disability in humans and represents a challenging problem in microsurgery. Physiologic repair at increasing intervals after the acute phase of injury results in progressively worse recovery, emphasizing the importance of rapid and timely reinnervation to optimize endorgan viability. Despite recent advances in microsurgical techniques, imperfect reinnervation results in partial return of neuromuscular function, even in the mildest neuropraxias. Axonal repair of mature neurons involves a complex interaction of molecular events, suggesting that the presence of specific neuronotropic factors might enhance the regeneration process. Recombinant human fibroblast growth factor (FGF-1) has been shown to induce both rapid angiogenesis and neurogenesis through a synthetic conduit across a 15-mm surgical gap in the peripheral nerve of the rat. Evidence of newly formed neural structures was confirmed postoperatively by histological examination in a temporal fashion over a 24-week interval. Functional motor recovery of regenerated nerves was evaluated by determining the amplitude and latency of compound muscle action potentials in treated animals. Electrophysiology studies demonstrated consistent return of motor function in 43 and 57% of animals harboring an FGF-1 conduit at 8- and 24-week intervals, respectively. None of the control animals exhibited restoration of motor function. Collectively, these data suggest that FGF may serve as an important mediator of controlled growth during peripheral nerve regeneration.

Action Potentials↗
PubMed1993

Physical mapping of four serpin genes: alpha 1-antitrypsin, alpha 1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome I4q32.1.

Alpha 1-antitrypsin (alpha 1AT; protease inhibitor [PI] locus), alpha 1-antichymotrypsin (alpha 1ACT; AACT locus), corticosteroid-binding globulin (CBG; CBG locus), and protein C inhibitor (PCI; PCI locus) are members of the serine protease inhibitor (serpin) superfamily. A noncoding PI-like (PIL) gene has been located 12 kb 3' of the PI gene. The PI, PIL, and AACT loci have been localized to 14q32.1, the CBG locus has been localized to 14q31-14q32.1, and PCI has been mapped to chromosome 14. Genetic linkage analysis suggests tight linkage between PI and AACT. We have used pulsed-field gel electrophoresis to generate a physical map linking these five serpin genes. The order of the genetic loci is AACT/PCI-PI-PIL-CBG, with a maximum distance of about 220 kb between the AACT/PCI and PI genes. These genes form a PI cluster at 14q32.1, similar to that of the homologous genes on murine chromosome l2. The close proximity of these genes has implications for disease-association studies.

Chromosomes, Human, Pair 14↗
PubMed1992

Consumer product aspiration and ingestion in children: analysis of emergency room reports to the National Electronic Injury Surveillance System.

Inadvertent aspiration or ingestion of products in children is a reportable problem. The National Electronic Injury Surveillance System (NEISS) monitors 119 hospitals for product (nonfood) hazards through a network of emergency room physicians. Coins (52%) remain the most frequently ingested object (1988-1989). Pins, including nails and bolts, are second in rank. Spheres (eg, balls) are the most common cause of death. Most deaths (97%) occur in the home. Younger children (13.4 versus 22.7 months) are more at risk for death. This analysis suggests that shape, as well as availability, is important in children's injuries and deaths. Accurate reporting to NEISS of all aspirated objects remains essential so that product safety and the public's health can be improved. Food product injuries, however, are not reported to NEISS.

Accidents, Home↗