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Showing papers by "Michael Boehnke published in 1991"


Journal Article
TL;DR: Alternative nonparametric and maximum-likelihood methods for the analysis of RHs that use information on many loci simultaneously, including information on partially typed hybrids are described, which provides a statistically more efficient solution to the locus-ordering problem.
Abstract: 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.

292 citations


Journal Article
TL;DR: A method for allele frequency estimation for data on relatives that is based on standard methods of pedigree analysis that makes use of all available marker information while correctly taking into account the dependence between relatives is described.
Abstract: 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.

278 citations


Journal ArticleDOI
TL;DR: A family in which a Thr58Arg rhodopsin mutation co-segregates with the disease phenotype of autosomal dominant retinitis pigmentosa (RP) in 16 family members is reported, showing a later onset of symptoms, with night blindness first noticed between ages 12 to 24 years.

75 citations


Journal Article
TL;DR: Two families with members affected with both von Willebrand disease and hereditary hemorrhagic telangiectasia are studied by RFLP analysis to determine whether there is a molecular basis for the association of vWD and HHT.
Abstract: 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.

39 citations