Showing papers by "Alejandro A. Schäffer published in 1996"
TL;DR: In this article, genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380.
Abstract: Parkinson9s disease (PD) is the second most common neurodegenerative disorder after Alzheimer9s disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.
753 citations
TL;DR: The implementation in FASTLINK of some algorithmic improvements to partly address the problems of pedigree loops and unknown genotypes is described.
Abstract: There seems to be no limit to the complexity of computations that genetic linkage analysts want to do. Two primary factors that increase the length of computations are pedigree loops and unknown genotypes. I describe the implementation in FASTLINK of some algorithmic improvements to partly address the problems of pedigree loops and unknown genotypes. LINKAGE is by far the most popular software package to do lod score computations on disease pedigrees. FASTLINK is derived from LINKAGE 5.1 and compatible with it. In contrast to LINKAGE, FASTLINK has the virtues that it is faster sequentially, runs well in parallel, is more robust against errors, and includes substantial new documentation. One of the new improvements allows the detection of violation of mendelian rules of inheritance in input pedigree files with loops. This error-detection capability was not provided in any previous version of LINKAGE or FASTLINK.
129 citations
TL;DR: Baker's theory of parameterized string matching is extended to algorithms that match multiple patterns in a text, and is first considered where the patterns are fixed and preprocessed once, and then the case where the pattern set can change by insertions and deletions.
38 citations
TL;DR: It is concluded that hypothalamic hamartoma is not specific to PHS and that the dominant hand malformation in one of the families was a coincidence, and the relationship of PHS to Smith-Lemli-Opitz syndrome is evaluated.
Abstract: Pallister-Hall syndrome (PHS) was originally described in 1980 in six sporadic cases of children with structural anomalies including hypothalamic hamartoma, polydactyly, imperforate anus, and renal and pulmonary anomalies. In 1993, the first familial cases were reported, including affected sibs and vertical transmission. Three of these families are sufficiently large to allow initial evaluation by linkage studies to candidate genes or loci. We have evaluated candidate loci for PHS based on three clinical observations. The first is a patient with PHS-like malformations, including a hypothalamic hamartoma, and an unbalanced translocation involving 7q and 3p. The second is a family with familial PHS where the founder's father had an autosomal dominant hand malformation previously mapped to 17q. The third is the phenotypic overlap of PHS and Smith-Lemli-Opitz syndrome. In this report, we exclude these loci as candidates for linkage to the PHS phenotype on the basis of lod scores of less than-2.0. We conclude that hypothalamic hamartoma is not specific to PHS and that the dominant hand malformation in one of the families was a coincidence. To evaluate the relationship of PHS to Smith-Lemli-Opitz syndrome, we analysed levels of cholesterol and intermediate metabolites of the later stages of cholesterol biosynthesis. There is no evidence of a generalised disorder of cholesterol biosynthesis in patients with familial PHS. On genetic and biochemical grounds, we conclude that PHS and Smith-Lemli-Opitz syndrome are not allelic variants of a single locus.
9 citations