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Biomedical subjects

J G Hall

Publications and source records attributed to J G Hall.

At least 37 records · Page 2Linked to original sources
PubMed1999

Polymorphism identification and quantitative detection of genomic DNA by invasive cleavage of oligonucleotide probes.

Flap endonucleases (FENs) isolated from archaea are shown to recognize and cleave a structure formed when two overlapping oligonucleotides hybridize to a target DNA strand. The downstream oligonucleotide probe is cleaved, and the precise site of cleavage is dependent on the amount of overlap with the upstream oligonucleotide. We have demonstrated that use of thermostable archaeal FENs allows the reaction to be performed at temperatures that promote probe turnover without the need for temperature cycling. The resulting amplification of the cleavage signal enables the detection of specific DNA targets at sub-attomole levels within complex mixtures. Moreover, we provide evidence that this cleavage is sufficiently specific to enable discrimination of single-base differences and can differentiate homozygotes from heterozygotes in single-copy genes in genomic DNA.

Archaeoglobus fulgidus↗
PubMed1997

Mosaicism in pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a spondylo-epi-metaphyseal dysplasia characterized by disproportionate short stature, generalized ligamentous laxity, and precocious osteoarthritis. PSACH is caused by mutations in the cartilage oligomeric matrix protein (COMP) gene, which codes for a noncollagenous protein expressed in the territorial matrix of chondrocytes. Autosomal dominant inheritance has been demonstrated in many families; however, autosomal recessive inheritance has been suggested in some severe familial cases. Alternatively, germline/somatic mosaicism has been proposed and is credible, since it has been shown that dominantly inherited and sporadic cases of PSACH are caused by the same genetic defect. Here, we present evidence demonstrating somatic mosaicism in two PSACH families that were originally considered to represent autosomal recessive inheritance. The results of this study suggest that autosomal recessive inheritance is unlikely and all cases of PSACH should be studied for mutations in COMP.

Achondroplasia↗
PubMed1997

Bone dysplasias, nontraditional mechanisms of inheritance and monozygotic twins.

New developments in the area of cytogenetics and molecular genetics have suggested a variety of newly recognized mechanisms that result in human genetic disorders. These mechanisms are being observed among individuals with bone dysplasias. Mosaicism imprinting, parent-of-origin differences, uni- parental disomy (UPD) and mono-zygotic twinning represent mechanisms which modify the phenotypic expression of the bone dysplasia.

Bone Diseases, Developmental↗
PubMed1997

Genomic imprinting: nature and clinical relevance.

Molecular genetic techniques allow investigators to trace chromosomes and genes from parent to child and, in a single individual, from tissue to tissue. These techniques have uncovered a new type of gene control in which the allele from one parent is expressed and the allele from the other parent is not. This differential expression is called genomic imprinting. It may lead to phenotypic differences when inheritance is from the mother versus the father. Genomic imprinting has been observed in a number of disorders having to do with growth, behavior, and abnormal cell growth. It is important to be aware that such a phenomenon exists and to consider it when making diagnoses and determining therapy.

Alleles↗
PubMed1997

Arthrogryposis multiplex congenita: etiology, genetics, classification, diagnostic approach, and general aspects.

Arthrogryposis is a sign associated with many specific conditions and syndromes. It is a term used to describe the presence of multiple joint contractures that are present at birth. It can be seen in isolation or in association with other congenital abnormalities as part of a syndrome with or without central nervous system involvement. The exact pathogenesis of arthrogryposis is unknown, but all involve fetal akinesia (decreased fetal movement) with subsequent joint contractures. In this article I describe the causes, genetic aspects, classification, and approach to diagnosis.

Arthrogryposis↗
PubMed1996

Segregation analysis of microcephaly.

Microcephaly is a heterogeneous disorder with genetic and environmental causes. However, there is little information on what proportion of cases are caused by inherited susceptibility, or the mode of inheritance in familial cases. To address these questions, we have performed classical and complex segregation analyses for microcephaly on 2 sets of family data collected from genetic counseling clinics in Vancouver and Jerusalem. These samples consisted of 143 affected individuals in 127 families ascertained from Vancouver, and 101 affected individuals in 59 families ascertained from Jerusalem. The results of the segregation analyses for the Vancouver sample indicated that approximately half of all microcephaly cases were due to highly penetrant recessive mutant alleles, with the remainder being sporadic. Although a recessive model allowing for the occurrence of sporadic cases fit the data from Vancouver best, a dominant model could not be statistically rejected. The classical segregation analysis on the Jerusalem sample suggested that both a dominant model with 29% of the cases being sporadic and a purely recessive model provided adequate fit to the data. Although the complex segregation analysis of this sample indicated that a dominant model provided a more parsimonious explanation for the observed familial variation, a recessive model was only marginally rejected. It should be noted that in the Jerusalem sample, families tended to be ascertained in the genetic counseling clinic only after the birth of a second affected child. This could be a potential bias which could inflate the segregation ratio, thus giving the impression of dominant inheritance. Our analyses, while confirming the complex nature of the cause of microcephaly, indicate that it may be necessary to await the results of genetic linkage analysis before a definitive mode of inheritance can be determined.

Alleles↗
PubMed1996

NUC-2, a component of the phosphate-regulated signal transduction pathway in Neurospora crassa, is an ankyrin repeat protein.

In response to phosphorus limitation, the fungus Neurospora crassa synthesizes a number of enzymes that function to bring more phosphate into the cell. The NUC-2 protein appears to sense the availability of phosphate and transmits the signal downstream to the regulatory pathway. The nuc-2+ gene has been cloned by its ability to restore growth of a nuc-2 mutant under restrictive conditions of high pH and low phosphate concentration. We mapped the cloned gene to the right arm of linkage group II, consistent with the chromosomal position of the nuc-2 mutation as determined by classical genetic mapping. The nuc-2' open reading frame is interrupted by five introns and codes for a protein of 1066 amino acid residues. Its predicted amino acid sequence has high similarity to that of its homolog in Saccharomyces cerevisiae, PHO81. Both proteins contain six ankyrin repeats, which have been implicated in the cyclin-dependent kinase inhibitory activity of PHO81. The phenotypes of a nuc-2 mutant generated by repeat-induced point mutation and of a strain harboring a UV-induced nuc-2 allele are indistinguishable. Both are unable to grow under the restrictive conditions, a phenotype which is to some degree temperature dependent. The nuc-2+ gene is transcriptionally regulated. A 15-fold increase in the level of the nuc-2+ transcript occurs in response to a decrease in exogenous phosphate concentration.

Amino Acid Sequence↗
PubMed1996

Arthrogryposis associated with unsuccessful attempts at termination of pregnancy.

We report three cases of failed termination of pregnancy in which the children were subsequently born with arthrogryposis (AMC) (multiple congenital contractures). Arthrogryposis is a sign with many causes. We suggest that the multiple congenital contractures seen in these children are due to vascular compromise during the attempted termination with secondary loss of functional neurons leading to fetal akinesia and subsequent contractures. Two of the children have additional evidence of intrauterine vascular compromise. Limitation of movement secondary to the rupture of the fetal membranes and continuous leakage of amniotic fluid after the attempted termination may have compounded the contractures in two of the children.

Abortion, Incomplete↗
PubMed1996

Syndrome of multiple epiphyseal dysplasia (ribbing type) with rhizomelic shortness, cleft palate, and micrognathia in two unrelated patients.

We report on two unrelated patients with an apparently new syndrome. In each family they are the only affected members, their parents are not consanguineous, and paternal and maternal ages are not advanced. At birth each patient was noted to have a marked Robin phenotype (cleft of the secondary palate and micrognathia) plus rhizomelic shortness. Delay in the appearance of long bone epiphyses was noted and followed by small fragmented and later very flat epiphyses of all long bones. The fibulae are short and radial heads dislocated. Scoliosis and marked genu valgum developed in both. Both patients have normal intelligence, vision, and hearing. Both have mildly upward slanting palpebral fissures, broad nasal tip, and apparent hypertelorism.

Adult↗