Showing papers by "Michael Boehnke published in 1992"

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

Abstract: 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.

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

Abstract: 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 year 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 maxmal femoral BMD.

Multipoint analysis for radiation hybrid mapping.

Abstract: 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 or...

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

Abstract: 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.