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Biomedical subjects

A D Roses

Publications and source records attributed to A D Roses.

At least 217 records · Page 12Linked to original sources
PubMed1992

Linkage studies in Charcot-Marie-Tooth disease type 2: evidence that CMT types 1 and 2 are distinct genetic entities.

Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, is a progressive sensorimotor neuropathy divided into types 1 and 2 based upon electrophysiologic and neuropathologic differences. The more common autosomal dominant form of CMT type 1 (hereditary motor and sensory neuropathy type I) is genetically heterogeneous, with genes located on chromosomes 1 (type 1B) or 17 (type 1A). However, no locus for CMT type 2 is known. We have performed linkage studies on three large multigenerational CMT type 2 families using probes from chromosome 1 and chromosome 17, which span their respective linkage regions. Multipoint analysis of the chromosome 17 markers excluded linkage over an area of 45 cM--15 cM proximal and 30 cM distal to the region containing CMT type 1A. Multipoint analysis of the chromosome 1 markers exclude linkage 15 cM proximal and 20 cM distal to FC-gamma-RII in the region of CMT 1B. These data indicate that CMT type 2 is genetically distinct from CMT type 1.

Adolescent↗
PubMed1992

Recombination of 4p16 DNA markers in an unusual family with Huntington disease.

The Huntington disease (HD) mutation has been localized to human chromosome 4p16, in a 6-Mb region between the D4S10 locus and the 4p telomere. In a report by Robbins et al., a family was identified in which an affected individual failed to inherit three alleles within the 6-Mb region originating from the parental HD chromosome. To explain these results, it was suggested that the HD locus (HD) lies close to the telomere and that a recombination event took place between HD and the most telomeric marker examined, D4S90. As a test of this telomere hypothesis, we examined six members of this family, five of whom are affected with HD, for the segregation of 12 polymorphic markers from 4p16, including D4S169, which lies within 80 kb of the 4p telomere. We separated, in somatic cell hybrids, the chromosomes 4 from each family member, to determine the phase of marker alleles on each chromosome. We excluded nonpaternity by performing DNA fingerprint analyses on all six family members, and we found no evidence for chromosomal rearrangements when we used high-resolution karyotype analysis. We found that two affected siblings, including one of the patients originally described by Robbins et al., inherited alleles from the non-HD chromosome 4 of their affected parents, throughout the 6-Mb region. We found that a third affected sibling, also studied by Robbins et al., inherited alleles from the HD chromosome 4 of the affected parent, throughout the 6-Mb region. Finally, we found that a fourth sibling, who is likely affected with HD, has both a recombination event within the 6-Mb region and an additional recombination event in a more centromeric region of the short arm of chromosome 4. Our results argue against a telomeric location for HD and suggest that the HD mutation in this family is either associated with DNA predisposed to double recombination and/or gene conversion within the 6-Mb region or is in a gene that is outside this region and that is different from that mutated in most other families with HD.

Adult↗
PubMed1992

Linkage studies in facioscapulohumeral muscular dystrophy (FSHD).

Facioscapulohumeral muscular dystrophy (FSHD) has been localized to the 4q35-qter region of chromosome 4. Linkage analyses of two polymorphic markers from the region, D4S139 and D4S163, have been carried out using four large multigenerational FSHD families. The results indicate that both markers are closely linked to FSHD, with D4S139 being the closest proximal marker to FSHD.

Chromosome Mapping↗
PubMed1991

Alzheimer's disease cell bank.

The seventh sentence of the first paragraph of the letter from P. W. Anderson, E. Abrahams, and R. Laughlin that appeared in the issue of 1 March (pp. 1005-1006) was printed incorrectly. It should have read, "Others, such as the ;anyon' proponents, a group at Bell laboratories and Rutgers, and another at Princeton, are sure that this system is not a Fermi liquid."

Alzheimer Disease↗
PubMed1991

Diagnostic criteria for multiple sclerosis research involving multiply affected families.

Existing diagnostic criteria for multiple sclerosis present significant limitations when assessing multiplex families for three reasons: (1) restricting age of onset to 10 to 50 years is likely to exclude 10% of patients known to have a later onset, (2) diagnoses based on subjective information can potentially result in a false-positive diagnosis, and (3) including progressive myelopathies occurring within families, particularly when highly symmetrical, may result in the improper inclusion of genetically determined neurological diseases such as familial spastic paraparesis. The validity of any molecular genetic approach for determining disease susceptibility critically depends on diagnostic accuracy. We present adapted diagnostic criteria that address each of these diagnostic pitfalls unique to multiplex multiple sclerosis family research.

Family↗
PubMed1991

Genetic linkage analysis of nerve growth factor (beta) in familial Alzheimer's disease.

Recent studies have not shown linkage of late-onset (mean age, greater than 60 years) familial Alzheimer's disease (FAD) to the chromosome 21 locus reported linked to early-onset FAD. Beta nerve growth factor (beta-NGF) has been considered a candidate gene in the pathogenesis and therapy of FAD, based on its localization in the cortex and hippocampus and its ability to enhance the growth and survival of cholinergic neurons. A 1.5-kb fragment of the beta-NGF gene was used to detect a BglII restriction fragment length polymorphism, which was then used for linkage analysis. A total of 30 families (27 late onset) with 147 affected members were studied. Close linkage (theta less than or equal to 0.03, z less than or equal to -2.00) of late-onset FAD with beta-NGF was excluded. Two apparent obligate crossovers between affected members were detected in different autopsy-confirmed families. Based on these results, beta-NGF is not the gene responsible for late-onset FAD in the families analyzed.

Aged↗
PubMed1991

Expression of mRNAs in human thymus coding for the alpha 3 subunit of a neuronal acetylcholine receptor.

We report the isolation of clones from a human thymus cDNA library that code for the alpha 3 subunit of a neuronal acetylcholine receptor (AcChR). The clones hybridize to one major 3.0-kb mRNA thymic species and four minor ones of approximately 2.3, 4.0, 5.0, and 6.5 kb, but they do not hybridize to human muscle mRNA. These clones may be of value in defining the cholinergic thymic makeup and the putative role that a thymic AcChR may have in the triggering and/or maintenance of an anti-AcChR response in the autoimmune condition myasthenia gravis.

Amino Acid Sequence↗
PubMed1991

Support of linkage of Gerstmann-Sträussler-Scheinker syndrome to the prion protein gene on chromosome 20p12-pter.

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a human transmissible spongiform encephalopathy recently linked to the human analog of the prion protein gene (PRNP) on chromosome 20p. We have studied a large German GSS family for linkage to PRNP and have obtained a peak lod score of 1.15 at a recombination fraction (theta) of 0.00. This result provides additional evidence that GSS is linked to a mutation in codon 102 of the PRNP gene. Combining our data with linkage data previously reported yields a peak lod score of 4.52 at theta = 0.0. No evidence for linkage heterogeneity was found in the combined data set.

Chromosomes, Human, Pair 20↗
PubMed1991

Localization of Charcot-Marie-Tooth disease type 1a (CMT1A) to chromosome 17p11.2.

Charcot-Marie-Tooth (CMT) disease type 1a has been previously localized to chromosome 17 using the markers D17S58 and D17S71. In that report we were unable to provide unequivocal localization of the CMT1A gene on either the proximal p or the q arm. Therefore, data from one additional CMT1A family and typing of other probes spanning the pericentromeric region of chromosome 17 (D17S73, D17S58, D17S122, D17S125, D17S124) were analyzed. Multipoint analysis demonstrates convincing evidence (log likelihood difference greater than 5) that the CMT1A gene lies within 17p11.2 and most likely between the flanking markers D17S122 and D17S124.

Charcot-Marie-Tooth Disease↗
PubMed1991

Linkage studies in tuberous sclerosis. Chromosome 9?, 11?, or maybe 14!

Published reports show linkage of tuberous sclerosis (TSC) to either chromosome 9 in some families or chromosome 11 in other families. We studied 243 individuals (82 with TSC) from 16 multigenerational TSC families. The diagnosis of TSC conformed to the criteria of Gomez. Penetrance was estimated at 0.90. DNA markers were analyzed using Southern blotting, probe hybridization, autoradiography, and genetic linkage analysis. Two-point lod scores for TSC were calculated for 43 genetic markers distributed over 11 chromosomes. Tests for homogeneity rejected the null hypothesis of homogeneity. Linkage to TSC was excluded (z less than or equal to -2, theta greater than or equal to 0.05) for 23 of these markers including 9q34 and 11q markers. One family gave z(theta max) = 1.8, theta max = 0.001 with ABO (on 9q34), and two other families attained lod scores greater than 1 for 9q34-region markers. The lod score for TSC versus chromosome 14 marker pAW101 (D14S1) was z(theta max) = 1.98, theta max = 0.15. A single large family has overall negative lod scores for markers localized to both chromosome 9 and chromosome 11. These data confirm genetic heterogeneity in TSC and suggest linkage of some families to 9q34. Furthermore, the data suggest that 14q may be an interesting area.

Chromosome Mapping↗
PubMed1991

APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease.

The amyloid precursor protein (APP) gene codes for the precursor to the beta-protein found in the amyloid deposits of Alzheimer disease (AD). Recently Goate et al. identified in codon 717 of this gene a missense mutation which segregates with AD in a familial AD (FAD) kindred. The same mutation was also found in affected subjects from a second FAD family but not in other FAD families or in normal controls. The following work was undertaken to determine the frequency of the codon 717 mutation in FAD and nonfamilial AD cases and in normal controls. We tested 76 FAD families, 127 "sporadic" AD subjects, 16 Down syndrome cases, and 256 normal controls for this mutation, and none were positive. We also tested for the APP codon 693 mutation associated with hereditary cerebral hemorrhage with amyloidosis-Dutch type, for PRIP gene missense mutations at codons 102, 117, and 200, and for the PRIP insertion mutations which are associated with Creutzfeld-Jakob disease and Gerstmann-Straussler Scheinker syndrome. No examples of these mutations were found in our population. Thus these APP and PRIP mutations are rare in both FAD and nonfamilial AD.

Adult↗
PubMed1990

Isolation and localization of a slow troponin (TnT) gene on chromosome 19 by subtraction hybridization of a cDNA muscle library using myotonic dystrophy muscle cDNA.

Subtraction hybridization techniques were used to isolate 91 cDNA clones which are overexpressed in normal control skeletal muscle relative to muscle from patients with myotonic muscular dystrophy. The gene responsible for myotonic dystrophy (DM) has been localized to the 19q13.2-13.3 region of chromosome 19. To test as a candidate gene for DM, clones which represent differences in transcription are analyzed for localization to chromosome 19. One clone, designated MSL 366, was found to be on the long arm of chromosome 19 distal to the CKMM gene at 19q13.2. Sequence analysis confirmed that MSL 366 is the cDNA for human slow skeletal muscle troponin T. A genomic clone has been isolated and linkage studies with DM are in progress.

Base Sequence↗