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M Boehnke

Publications and source records attributed to M Boehnke.

At least 19 recordsLinked to original sources
PubMed1992

Genetic association and linkage analysis of the apolipoprotein CII locus and familial Alzheimer's disease.

We previously reported a genetic association between the 3.5 kb (F) Taq I restriction fragment length polymorphism allele of the apolipoprotein CII gene on chromosome 19 and familial Alzheimer's disease. Here, we report an additional analysis of this association performed on an expanded and better defined data set of 23 families with familial Alzheimer's disease. The F allele frequency in affected family members in the expanded set was 0.62 +/- 0.06 (mean +/- standard error, n = 51 subjects), which differed significantly from a frequency of 0.39 +/- 0.02 (n = 226) for unrelated control subjects (Z = 3.75, p less than 0.0002). These results are consistent with our previous findings and suggest an association between the F allele of apolipoprotein CII and familial Alzheimer's disease. When the apolipoprotein CII locus was tested for linkage to familial Alzheimer's disease, LOD scores summed for the complete group of families were negative and close linkage was excluded. Close linkage was also excluded for early-onset families (mean onset age less than or equal to 60 years), but small positive LOD scores were obtained for late-onset kindreds.

Alleles↗
PubMed1992

Familiality and partitioning the variability of femoral bone mineral density in women of child-bearing age.

The contributions of polygenic loci and environmental factors to femoral bone mineral density (BMD) in g/cm2) variability were estimated in modified family sets consisting of women of child-bearing age. Femoral BMDs were measured in 535 women who were members of 137 family sets consisting minimally of an index, her sister, and unrelated female control. The family set could also include multiple sisters and first cousins. Women included in these family sets were all between 20 and 40 years of age to minimize the cohort effects of maturation and menopause on measures of BMD. BMDs were measured at three femoral sites using dual photon densitometry. Values were regressed on age and Quetelet Index which explained 13-15% of the variability in BMD (dependent on site). Subsequent variance components analysis on the residuals indicated that unmeasured polygenic loci accounted for substantial additional variability: 67% for femoral neck, 58% for Wards triangle, and 45% for trochanter. These results suggest that polygenic loci account for approximately half of the variability in maximal femoral BMD.

Adult↗
PubMed1992

Radiation hybrid map spanning the Huntington disease gene region of chromosome 4.

Radiation hybrid (RH) mapping was used to construct a map of 11 markers in the distal 4 Mb of the short arm of chromosome 4, the region containing the Huntington disease gene. Two different methods for deriving the order of the markers were compared and both arrived at the same order as being the most likely. This order is also consistent with both the physical map constructed using pulsed-field gel electrophoresis (PFGE) and the meiotic linkage map. Comparing the RH map to the map determined by PFGE provided the means to equate RH map units (centirays) with actual physical distance in kilobases of DNA. In addition, a simple procedure for reducing the complexity of human DNA in radiation hybrids is described. One cell line isolated using this procedure contains, as its only human DNA, approximately 2 Mb surrounding the Huntington disease gene.

Chromosome Mapping↗
PubMed1992

Cavernous hemangioma of the adrenal gland.

Cavernous hemangiomas of the adrenal gland are rare. We report on a patient with a left adrenal hemangioma successfully treated by radical excision. The literature pertaining to this interesting pathological condition is reviewed.

Adrenal Gland Neoplasms↗
PubMed1992

A radiation hybrid map of the region on human chromosome 22 containing the neurofibromatosis type 2 locus.

We describe a high-resolution radiation hybrid map of the region on human chromosome 22 containing the neurofibromatosis type 2 (NF2) gene. Eighty-five hamster-human somatic cell hybrids generated by X-irradiation and cell fusion were used to generate the radiation hybrid map. The presence or absence of 18 human chromosome 22-specific markers was determined in each hybrid by using Southern blot hybridization. Sixteen of the 18 markers were distinguishable by X-ray breakage in the radiation hybrids. Analysis of these data using two different mathematical models and two different statistical methods resulted in a single framework map consisting of 8 markers ordered with odds greater than 1000:1. The remaining nonframework markers were all localized to regions consisting of two adjoining intervals on the framework map with odds greater than 1000:1. Based on the RH map, the NF2 region of chromosome 22, defined by the flanking markers D22S1 and D22S28, is estimated to span a physical distance of approximately 6 Mb and is the most likely location for 9 of the 18 markers studied: D22S33, D22S41, D22S42, D22S46, D22S56, LIF, D22S37, D22S44, and D22S15.

Animals↗
PubMed1992

A radiation hybrid map of the proximal short arm of the human X chromosome spanning incontinentia pigmenti 1 (IP1) translocation breakpoints.

Radiation hybrid mapping was used in combination with physical mapping techniques to order and estimate distances between 14 loci in the proximal region of the short arm of the human X chromosome. A panel of radiation hybrids containing human X-chromosomal fragments was generated from a Chinese hamster-human cell hybrid containing an X chromosome as its only human DNA. Sixty-seven radiation hybrids were screened by Southern hybridization with sets of probes that mapped to the region Xp11.4-Xcen to generate a radiation hybrid map of the area. A physical map of 14 loci was constructed based on the segregation of the loci in the hybrid clones. Using pulsed-field gel electrophoresis (PFGE) analyses and a somatic cell hybrid mapping panel containing naturally occurring X; autosome translocations, the order of the 14 loci was verified and the loci nearest to the X-chromosomal translocation breakpoints associated with the disease incontinentia pigmenti 1 (IP1) were identified. The radiation hybrid panel will be useful as a mapping resource for determining the location, order, and distances between other genes and polymorphic loci in this region as well as for generating additional region-specific DNA markers.

Animals↗
PubMed1992

Bayesian methods and optimal experimental design for gene mapping by radiation hybrids.

Radiation hybrid mapping is a somatic cell technique for ordering human loci along a chromosome and estimating the physical distance between adjacent loci. The present paper considers a realistic model of fragment generation and retention. This model assumes that fragments are generated in the ancestral cell of a clone according to a Poisson breakage process along the chromosome. Once generated, fragments are independently retained in the clone with a common retention probability. Based on this and less restrictive models, statistical criteria such as minimum obligate breaks, maximum likelihood, and Bayesian posterior probabilities can be used to decide order. Distances can be estimated by either maximum likelihood or Bayesian posterior means. The model also permits rational design of radiation dose for optimal statistical precision. A brief examination of some real data illustrates our criteria and computational algorithms.

Algorithms↗
PubMed1992

Multipoint analysis for radiation hybrid mapping.

Radiation hybrid mapping is a somatic cell genetic technique that permits construction of fine-structure maps of human chromosomes. Radiation hybrid mapping uses X-ray breakage of chromosomes to order genetic loci and to estimate distances between them. Cox and colleagues described radiation hybrid mapping and derived methods for locus ordering based on two-point statistical analysis of radiation hybrid mapping data. In this paper, I describe alternative non-parametric and likelihood methods for radiation hybrid mapping that make use of information on many loci simultaneously, and efficiently include information on partially typed radiation hybrids. Locus orders are selected by minimum number of obligate chromosome breaks or maximum likelihood. I demonstrate the utility of these methods with an application to data on 14 markers and 99 hybrids for human chromosome 21.

Chromosome Aberrations↗
PubMed1992

Clinical use of recombinant plasminogen activator for intraocular fibrinolysis.

In a preliminary clinical study, recombinant tissue plasminogen activator (rt-PA) was injected into the anterior chamber of 18 eyes and into the vitreous cavity of 2 eyes in a total of 20 patients. The clinical indications were severe fibrin formation after filtering operations for glaucoma (8 eyes), diabetic neovascular glaucoma (3), fibrin and hemorrhage after vitrectomy (3), keratoplasty (3), posterior chamber lens implantation (1), trauma (1), and endophthalmitis (1). Complete fibrinolysis within a minimum of 2 h was achieved in 81% of 26 injections. Although doses of about 12 micrograms rt-PA were generally given, in our observations, 6 micrograms proved to be sufficient for rapid fibrinolysis in selected cases. Injections of rt-PA should not be considered before the 3rd postoperative day so as to avoid rebleeding and recurrent fibrin formation. No toxic intraocular side effect was observed after the use of rt-PA in this study.

Adult↗
PubMed1991

Rhodopsin Thr58Arg mutation in a family with autosomal dominant retinitis pigmentosa.

The authors report a family in which a Thr58Arg rhodopsin mutation co-segregates with the disease phenotype of autosomal dominant retinitis pigmentosa (RP) in 16 family members. DNA sequence determination confirms the presence of the same mutation reported previously for one family apparently unrelated to the pedigree now reported. Features of RP in this family included a later onset of symptoms, with night blindness first noticed between ages 12 to 24 years. Although symptoms worsened with age, no complete blindness was observed even with advanced age. Results of psychophysical and electrophysiologic testing showed that a 19-year-old affected woman and her 65-year-old affected uncle had relatively similar extent of visual dysfunction, and that the vision of both was better than 2 of their relatives aged 37 and 53 years. This study presents a range of phenotypic similarities and differences observed between individuals whose RP appears to be caused by the same mutation.

Adult↗
PubMed1991

Diagnosis of human cytomegalovirus-induced retinitis in human immunodeficiency virus type 1-infected subjects by using the polymerase chain reaction.

In 13 of 16 AIDS patients with retinitis, a herpesviruslike infection was diagnosed by clinical investigation. In 12 of the 13 patients, human cytomegalovirus (HCMV) DNA was detected in 5 microliters of aqueous humor by using the polymerase chain reaction (PCR). In the aqueous humor of 12 control patients HCMV DNA could not be detected by PCR. PCR may be used to monitor specific antiviral long-term therapy in HCMV retinitis.

Base Sequence↗
PubMed1991

Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (IIe865 to Thr).

Reports of families with members affected with both von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia (HHT) suggest a possible relationship between these two disorders. vWD, the most common inherited bleeding disorder in humans, is due to either a quantitative or qualitative defect in von Willebrand factor (vWF). The gene for vWF has been cloned and mapped to chromosome 12 (12p12----12pter). HHT, an uncommon inherited bleeding disorder, is characterized by malformed, dilated, fragile blood vessels. The chromosomal location of the gene for HHT is unknown. We studied two families by RFLP analysis to determine whether there is a molecular basis for the association of vWD and HHT. Family A is affected with both type IIA vWD and HHT; family B is affected with HHT alone. Linkage of HHT to the vWF gene was not detected, and vWF was ruled out as a candidate gene for HHT. The vWF gene was found to be tightly linked to type IIA vWD in family A (lod score 3.61 at recombination fraction .00). By PCR and DNA sequence analysis of vWF exon 28, a single T----C transition resulting in the substitution of Thr for Ile865 was identified. This substitution is located immediately adjacent to two previously identified type IIA vWD mutations.

Alleles↗
PubMed1991

Statistical methods for multipoint radiation hybrid mapping.

On the basis of the earlier work of Goss and Harris, Cox et al. introduced radiation hybrid (RH) mapping, a somatic cell genetic technique for constructing fine-structure maps of human chromosomes. Radiation hybrid mapping uses X-ray breakage of chromosomes to order a set of genetic loci and to estimate distances between them. To analyze RH mapping data Cox et al. derived statistical methods that employ information on sets of two and four loci, to build an overall locus order. Here we describe alternative nonparametric and maximum-likelihood methods for the analysis of RHs that use information on many loci simultaneously, including information on partially typed hybrids. Combination of these multipoint methods provides a statistically more efficient solution to the locus-ordering problem. We illustrate our approach by applying it to RH mapping data on 14 markers in 99 radiation hybrids for the proximal long arm of human chromosome 21.

Algorithms↗
PubMed1991

Allele frequency estimation from data on relatives.

Given genetic marker data on unrelated individuals, maximum-likelihood allele-frequency estimates and their standard errors are easily calculated from sample proportions. When marker phenotypes are observed on relatives, this method cannot be used without either discarding a subset of the data or incorrectly assuming that all individuals are unrelated. Here, I describe a method for allele frequency estimation for data on relatives that is based on standard methods of pedigree analysis. This method makes use of all available marker information while correctly taking into account the dependence between relatives. I illustrate use of the method with family data for a VNTR polymorphism near the apolipoprotein B locus.

Alleles↗
PubMed1990

Molecular characterization of anti-idiotype antibody-resistant variants of a murine B cell lymphoma.

We have previously identified Id- tumor vaiants that emerge after anti-Id mAb therapy of the murine B cell lymphoma 38C13. This report characterizes the molecular basis for these variants. By using a modification of the polymerase chain reaction (PCR), mu and kappa Ig loci were sequenced from nine Id- variants derived directly by anti-Id immunoselection in vivo. Ig kappa loci sequence analysis was also performed from 10 additional variants amplified directly from tumor cells in vitro without immunoselection. We demonstrate that the molecular mechanism underlying tumor cell escape in this model is the spontaneous emergence of variants that have undergone kappa L chain gene "re-rearrangement" before positive selection by the anti-Id antibody. A second round of re-rearrangement was also demonstrated to occur within primary tumor variants. Re-rearrangement of the 38C13 tumor cell Ig kappa locus is strongly biased toward use of variable kappa genes within the conserved V kappa-Ox1 gene family, although their use is not exclusive. With the use of RNA PCR re-rearrangement was documented to occur in vitro at a frequency of approximately 1.0 x 10(-5)/cell. These findings may have important implications for the application of anti-Id antibodies as a therapeutic approach for human lymphomas and for understanding of the Ig gene rearrangement process.

Animals↗
PubMed1990

Family with dominantly inherited ataxia, amyotrophy, and peripheral sensory loss. Spinopontine atrophy or Machado-Joseph Azorean disease in another non-Portuguese family?

A family of German extraction with progressive ataxia, eye movement abnormalities, peripheral sensory loss, and spinal muscular atrophy of adult onset is described. Three members came to autopsy, and neuropathologically, the major changes included varying degrees of atrophy of the basis pontis and degeneration of the spinocerebellar tracts, Clarke's columns, anterior horn neurons, and fasciculus gracilis. The dentate nucleus was spared, and there was slight neuron loss from the substantia nigra in one patient. Clinically and neuropathologically, our family resembles that reported by Boller and Segarra as having spinopontine atrophy. However, several kindreds with similar findings have recently been described as having Azorean or Machado-Joseph disease in non-Portuguese families. Comparison of clinical and neuropathological features in spinopontine atrophy and Machado-Joseph disease, both in Portuguese and non-Portuguese families, reveals clinical and pathological similarities and differences between the two. The major differences in our patients include only minor extraocular movement abnormality and absence of protuberant eyes, and muscular rigidity clinically, and the sparing of the substantia nigra and the dentate nucleus neuropathologically. These differences suggest that spinopontine atrophy, as manifested in our family, is distinct from Machado-Joseph disease. Our family showed no linkage to the HLA locus on chromosome 6.

Adult↗