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Biomedical subjects

A D Roses

Publications and source records attributed to A D Roses.

At least 235 records · Page 13Linked to original sources
PubMed1990

Confirmation of linkage in von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease was initially reported to be linked to the RAF1 oncogene (3p25). We have ascertained and sampled two large multigenerational VHL families for linkage studies, in order to confirm the localization of the VHL gene as a prelude to fine mapping studies. The probes used in the analysis were p627 (RAF1) and pHeA12 (thyroid hormone receptor B) (3p24.1-3p22). VHL was analyzed as an autosomal dominant trait with age-dependent penetrance. The maximum lod score combining both families was z(theta) = 2.16 at theta = 0.0 for RAF1 and z(theta) = 2.20 at theta = 0.05 for thyroid hormone receptor B. Multipoint analysis using the RAF1 and thyroid hormone receptor B loci resulted in a peak lod score of 3.1 confirming linkage of VHL to this region of chromosome 3. However, the position of VHL relative to the two loci could not be established with certainty.

Angiomatosis↗
PubMed1990

Presymptomatic and prenatal diagnosis in myotonic dystrophy by genetic linkage studies.

Myotonic dystrophy (DM) is an autosomal dominant disorder with age-dependent penetrance and extremely variable expressivity. With the genetic markers CKMM and ApoC2, both of which are tightly linked and centromeric to DM, presymptomatic and prenatal diagnosis for myotonic dystrophy is available. We present the results of 4 families tested for carrier status of myotonic dystrophy by genetic linkage studies and define potential limitations of these studies. A protocol for genetic linkage studies in DM is outlined.

Adult↗
PubMed1989

Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17.

Charcot-Marie-Tooth disease Type 1 (CMT) is an inherited neuropathy with known genetic heterogeneity, with at least one autosomal dominant form (CMT Type 1b) linked to the Duffy region of chromosome 1. Autosomal dominant families not demonstrating linkage to the Duffy blood group marker have been designated CMT Type 1a. We report linkage of six CMT Type 1a families to the chromosome 17 markers EW301 (D17S58) and pA10-41 (D17S71) with maximum LOD scores of zeta = 10.49 at theta (maximum recombination fraction) = 0.05 and zeta = 7.36 at theta = 0.06, respectively.

Charcot-Marie-Tooth Disease↗
PubMed1989

Duchenne muscular dystrophy: detection of deletion carriers by spectrophotometric densitometry.

DNA isolated from a family segregating a deletion in the Duchenne muscular dystrophy gene and control families was digested with restriction enzymes, Southern transferred, and probed with a radioactive dystrophin cDNA probe. The resulting autoradiographs were analyzed with a densitometric spectrophotometer to detect carriers of the deletion. The carrier status of females in the deletion pedigree was independently determined by genomic probes and confirmed by densitometry. In many Duchenne families, deletions will only be observed using cDNA probes which show few restriction fragment length polymorphisms (RFLPs). Such deletions would normally have to be detected using dosage gels. The spectrophotometric densitometry technique used by us does not require dosage gels, and avoids problems arising from non-informative meioses and cross-overs. It should be possible to screen every family with an exon deletion by spectrophotometric densitometry provided the presently available cDNA is suitably reduced to produce fewer bands on autoradiographs.

Autoradiography↗
PubMed1989

Linkage analysis in the spinal muscular atrophy type of facioscapulohumeral disease.

Facioscapulohumeral disease is probably a heterogeneous disorder. We have ascertained and sampled two multigeneration families with the neurogenic form of this disorder, considered to be a type of spinal muscular atrophy (FSHSMA). The two families have 36 affected members. Linkage studies with 10 expressed and seven DNA restriction fragment length polymorphism (RFLP) markers failed to show significant linkage (Zmax greater than or equal to 3.00). However, two areas of probable linkage were defined on chromosomes 1p and 4q with the markers MNS (Zmax = 1.47 at theta max = 0.10) and PGM1 (Zmax = 0.94 at theta max = 0.001) respectively. We are using additional RFLPs from these and other areas of the human genome to screen these families for linkage to FSHSMA.

Chromosome Mapping↗
PubMed1989

Myotonic muscular dystrophy.

Myotonic muscular dystrophy is inherited as an autosomal dominant disease and affects many different organ systems. Genetic research has located the DM gene to chromosome 19. Using new DNA probes, highly accurate genetic counseling can be provided for families with DM. Isolation of the DM gene is expected in the near future and may allow planning of effective therapies.

Adult↗
PubMed1988

The molecular genetic revolution. Its impact on clinical neurology.

Applying the techniques of molecular genetics to the study of inherited diseases has made significant progress in recent years. The goal of this review is to update the clinical neurologist on the current state of progress in neurogenetic research. This progress has been primarily in the field of gene mapping--assigning a disease to its chromosomal locus. More recent advances have been in the cloning and study of the involved proteins in disorders such as Duchenne muscular dystrophy. The techniques are powerful and predictable in outcome. Knowledge in the field of genetic disorders will continue to expand rapidly. Many neurologic disorders have a genetic origin. As progress continues in the study of neurogenetic diseases, the clinical neurologist will have increasing options for diagnosis and counseling. Eventually, it is anticipated that therapeutic interventions will be available for some disorders. The clinical neurologist is a key worker in both research as well as the practical application of research advances. This review will focus initially and briefly on the basic methods of molecular genetic research. After the introduction to these methods, the remainder of the review will discuss recent advances in several neurogenetic disorders by the clinical neurologist. Gene therapy will also be briefly discussed.

Animals↗
PubMed1988

Prenatal diagnosis using deletion studies in Duchenne muscular dystrophy.

Accurate carrier testing and prenatal diagnosis in Duchenne muscular dystrophy (DMD) families is facilitated when an Xp21 deletion is found to be segregating within a family. We discuss the results of the DNA testing in two families, one in which DNA from affected males was available for study and the other in which no DNA from an affected male was available. Factors complicating the counselling of DMD deletion families are outlined.

Chromosome Deletion↗
PubMed1988

The poliovirus sensitivity (PVS) gene is on chromosome 19q12----q13.2.

Sensitivity to nonmodified poliovirus infection is an autosomal dominant trait, specific to primates. The gene for poliovirus sensitivity (PVS) is encoded on human chromosome 19. In order to sublocalize the PVS gene, we infected rodent-human hybrid cell lines that divide human chromosome 19 into four regions with poliovirus 1 and/or 3. When infected, these hybrid cell lines showed the typical cytopathic effect of poliovirus infection only if they contained 19q12----q13.2 as the smallest region of overlap. Appropriate negative and positive controls were used. PVS may be of relevance to myotonic dystrophy (DM) and the inherited motor neuron diseases: to DM because it localizes to the same region of chromosome 19 and to the inherited motor neuron diseases because it encodes a cell-surface receptor expressed on motor neurons.

Cell Line↗