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T C Matise

Publications and source records attributed to T C Matise.

At least 37 records · Page 2Linked to original sources
PubMed1995

A radiation hybrid map of 95 STSs spanning human chromosome 13q.

We have constructed a high-resolution physical map of the long arm of human chromosome 13 using a panel of 94 radiation hybrids. A comprehensive map of 95 chromosome 13-specific sequence tagged sites (STSs) spanning 13q from the presumed centromere at D13Z1 to the known telomere was obtained by multipoint maximum likelihood statistical methods. The 95 markers have an average retention frequency of 10%, with markers closer to the centromere having much greater retention frequencies (22-49%) than distal 13q markers (2-12%). The most likely radiation hybrid map localized the 95 STSs into 54 unique map positions, 34 with odds of 1000:1 or greater; the comprehensive map localized all but 17 STSs with odds exceeding 10:1. The total map length of 13q was 1302 cR9000 (range 6.4-94.4 cR9000) and a physical distance of 98 Mb, so that 1% breakage in the RH panel corresponds to 75 kb. A comparison of the comprehensive RH map to genetic maps of chromosome 13q shows identical locus orders for the common markers, with two exceptions over 1-cM distances. We discuss the possible relationships between the genetic and the radiation hybrid maps.

Animals↗
PubMed1995

Genome scanning for complex disease genes using the transmission/disequilibrium test and haplotype-based haplotype relative risk.

Two tests for allelic association were applied to a simulated complex disease for the Genetic Analysis Workshop 9. The transmission/disequilibrium test [Spielman et al., 1993] and the haplotype-based haplotype relative risk approach [Terwilliger and Ott, 1992] were used to detect disease-associated alleles in a set of 360 computer-simulated markers located on six chromosomes and genotyped in 200 nuclear families. This analysis emulates a genome-based search for linked markers. Computer simulations were also performed to clarify statistical properties of the TDT.

Alleles↗
PubMed1995

Towards fully automated genotyping: use of an X linked recessive spastic paraplegia family to test alternative analysis methods.

Advances in dinucleotide-based genetic maps open possibilities for large scale genotyping at high resolution. The current rate-limiting steps in use of these dense maps is data interpretation (allele definition), data entry, and statistical calculations. We have recently reported automated allele identification methods. Here we show that a 10-cM framework map of the human X chromosome can be analyzed on two lanes of an automated sequencer per individual (10-12 loci per lane). We use this map and analysis strategy to generate allele data for an X-linked recessive spastic paraplegia family with a known PLP mutation. We analyzed 198 genotypes in a single gel and used the data to test three methods of data analysis: manual meiotic breakpoint mapping, automated concordance analysis, and whole chromosome multipoint linkage analysis. All methods pinpointed the correct location of the gene. We propose that multipoint exclusion mapping may permit valid inflation of LOD scores using the equation max LOD-(next best LOD).

Alleles↗
PubMed1995

A gene for a severe lethal form of X-linked arthrogryposis (X-linked infantile spinal muscular atrophy) maps to human chromosome Xp11.3-q11.2.

X-linked arthrogryposis Type I (X-linked infantile spinal muscular atrophy) is a rare disorder showing hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have studied an X-linked arthrogryposis family using highly polymorphic microsatellite markers throughout the X chromosome. Meiotic breakpoint analysis (concordance analysis) based on shared regions of the founder X chromosome was successful in localizing the X-linked arthrogryposis gene to Xp11.3-q11.2. In this region, the highest two-point lod score was found with DXS991 (Zmax = 2.63, theta = 0.00). In multipoint linkage analysis covering the entire X chromosome, only the region defined by MAOB and DXS991 showed positive lod scores and all other regions showed negative lod scores. These data establish the first gene mapping assignment of an X-linked lethal form of human lower motor neuron disease.

Adolescent↗
PubMed1994

Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map.

High-resolution genetic linkage maps are indispensable for positional cloning of disease genes. Current procedures for map construction, although aided considerably by many existing computer programs, require extensive user-intervention at each of many repetitive steps. This is time consuming, labour intensive and increases the chance of error. We have developed an expert system computer program, MultiMap, which automates this step-by-step procedure. MultiMap is based on a novel map construction algorithm and allows investigator control of marker locus characteristics, such as informativeness, scorability or distance to nearest neighbours. We used MultiMap to construct a human genetic map at an average resolution of 6 cM, using published genotypes at 1266 microsatellite markers, and further extended this map by adding 397 VNTR and polymorphic gene markers.

Algorithms↗
PubMed1994

Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22.

Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology characterized by the absence of enteric ganglia in the distal colon. We have ascertained a large, inbred, Mennonite kindred which demonstrates a high incidence of Hirschsprung disease (HSCR). Genealogical analysis of all kinship relationships identified a single common ancestral couple for all parents of affected offspring. Segregation analysis yielded a segregation ratio of 10.67% for males and 5.45% for females. We searched for locations of the gene(s) responsible for HSCR in this pedigree by genotyping three small multicase families and locating genomic regions demonstrating identity-by-descent followed by linkage disequilibrium analysis of 28 additional nuclear families. Based on this novel strategy, we report the mapping of a new locus for HSCR to chromosome 13q22. Nine microsatellite markers spanning 10 cM in this region were genotyped on thirty-one nuclear families. Significant nonrandom association was detected with alleles at markers D13S162, D13S160, D13S170, and AFM240zg9. In addition, our studies reveal preliminary evidence for a genetic modifier of HSCR in this kindred on chromosome 21q22.

Chromosome Mapping↗
PubMed1994

Preliminary localization of a gene for autosomal dominant hypoparathyroidism to chromosome 3q13.

A large family in which hypoparathyroidism was observed to segregate as an autosomal dominant trait in three generations was identified. Mutation in the PTH gene was excluded by linkage and single-stranded conformational analysis. The hypocalcemic phenotype in this family was mapped by linkage analysis using short, tandem-repeat polymorphisms to the region of chromosome 3q13. A maximum lod score of 2.71 at theta = 0.0 was observed with marker D3S1303. Positive lod scores were observed at theta = 0.0 with markers flanking D3S1303. Multipoint linkage analysis gave a lod score of 2.71 for the region flanking D3S1303. Simulation using the computer program SLINK showed that a lod score of 2.71 at theta = 0.0 was the maximum lod score possible given the pedigree structure. The simulation also showed that given the structure of the pedigree the probability of observing a lod score of 2.71 at theta = 0.0 by chance was 1 in 1000. The data presented above provide important preliminary evidence supporting linkage to chromosome 3q13. This region contains a Ca(2+)-sensing receptor gene that is proposed as a key signal transduction element for changes in extracellular Ca2+ concentrations in mechanisms of regulation of PTH secretion from parathyroid cells. The mutation in this family may activate the Ca(2+)-sensing receptor suppressing PTH secretion and lowering the "set point" for serum calcium levels.

Chromosome Mapping↗
PubMed1994

Detection of tandem duplications and implications for linkage analysis.

The first demonstration of an autosomal dominant human disease caused by segmental trisomy came in 1991 for Charcot-Marie-Tooth disease type 1A (CMT1A). For this disorder, the segmental trisomy is due to a large tandem duplication of 1.5 Mb of DNA located on chromosome 17p11.2-p12. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within this duplication. To better understand how such a duplication might affect genetic analyses in the context of disease gene mapping, we studied the effects of marker duplication on transmission probabilities of marker alleles, on linkage analysis of an autosomal dominant disease, and on tests of linkage homogeneity. We demonstrate that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. In addition, we devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. We tested our methods through computer simulations and on CMT1A pedigrees genotyped at several chromosome 17 markers. On the simulated data, our method detected 96% of duplicated markers (with a false-positive rate of 5%). On the CMT1A data our method successfully identified two of three loci that are duplicated (with no false positives). This method could be used to identify duplicated markers in other regions of the genome and could be used to delineate the extent of duplications similar to that involved in CMT1A.

Alleles↗
PubMed1993

A linkage map of human chromosome 21:43 PCR markers at average intervals of 2.5 cM.

A genetic linkage map of human chromosome 21q (HC21q) containing 43 markers genotyped by the polymerase chain reaction in the CEPH pedigrees is presented. The markers placed on this map are highly polymorphic with an average heterozygosity of 61%. The average interval size of the markers localized at 1000:1 odds is 2.5 cM. The map has a total length of 65.5 cM, with male and female lengths of 47.7 and 83.3 cM, respectively. The genotypes used in the construction of this map were subjected to rigorous error checking, which is reflected in the shorter map length compared to previous maps; the estimated error rate in genotyping is less than 0.04%. As noted in previous linkage maps there is increased recombination in females on proximal HC 21q and in the male in a region near the telomere. This map of HC 21 represents a highly informative and dense meiotic linkage map and will be useful in linking disease phenotypes to loci on this chromosome.

Chromosome Mapping↗
PubMed1993

A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10.

Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby providing monogenic inheritance in some families. A maximum two-point lod score of 3.37 (theta = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model. Multipoint, affecteds-only and non-parametric analyses supported this finding and localize this gene to a region of approximately 7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2). The co-occurrence of these two entities in some families might be attributable to shared pathogenetic origins.

Alleles↗
PubMed1993

MultiMap: an expert system for automated genetic linkage mapping.

With the advent of the Human Genome Project, the ability to rapidly construct comprehensive and accurate linkage maps based on genetic marker data from family studies is an absolute necessity. In addition to their usefulness in localizing genes for both simple and complex disorders, linkage maps are invaluable tools for genetic counseling using linked marker genes. Several computer program packages are publicly available which aid in the construction of linkage maps by computing multipoint likelihoods for specified locus orders. However, these programs work in a step-by-step fashion, requiring intensive user-intervention and analysis at each step. Such a repetitive process is amenable to computerized automation. We have developed and tested an expert system computer program, MultiMap, for automated genetic linkage mapping. This program greatly reduces the amount of user-computer interaction, increasing the accuracy and speed with which a map can be constructed. In addition, because the total mapping time is greatly reduced through automation, it is now feasible to explore and compare various mapping heuristics and mapping criteria in order to develop the most appropriate approach, or set of approaches, for genetic linkage mapping. MultiMap need not be restricted to the construction of genetic maps, but could be adapted to aid in the automated construction of physical maps as well.

Automation↗