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T C Matise

Publications and source records attributed to T C Matise.

At least 19 recordsLinked to original sources
PubMed2001

A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4.

Substantial evidence supports the familial aggregation of exceptional longevity. The existence of rare families demonstrating clustering for this phenotype suggests that a genetic etiology may be an important component. Previous attempts at localizing loci predisposing for exceptional longevity have been limited to association studies of candidate gene polymorphisms. In this study, a genome-wide scan for such predisposing loci was conducted by using 308 individuals belonging to 137 sibships demonstrating exceptional longevity. By using nonparametric analysis, significant evidence for linkage was noted for chromosome 4 at D4S1564 with a MLS of 3.65 (P = 0.044). The analysis was corroborated by a parametric analysis (P = 0.052). These linkage results indicate the likelihood that there exists a gene, or genes, that exerts a substantial influence on the ability to achieve exceptional old age. Identification of the genes in humans that allow certain individuals to live to extreme old age should lead to insights on cellular pathways that are important to the aging process.

Aged↗
PubMed2001

Loss of heterozygosity for chromosome 14q in neuroblastoma.

BACKGROUND: Neuroblastoma is a genetically heterogeneous disease, with subsets of tumors demonstrating rearrangements of several genomic regions. Preliminary studies from several groups have identified loss of heterozygosity (LOH) for the long arm of chromosome 14 (14q) in 20-25% of primary neuroblastomas. PROCEDURE: To determine precisely the frequency and extent of 14q deletions, we performed LOH analysis for a large series of primary neuroblastomas using a panel of 11 highly polymorphic markers. RESULTS: LOH was detected in 83 of 372 tumors (22%). Although the majority of tumors with allelic loss demonstrated allelic loss for all informative markers, 13 cases showed LOH for only a portion of 14q. A single consensus region of deletion, which was shared by all tumors with 14q LOH, was defined within 14q23-q32 between D14S588 and the 14q telomere. Allelic loss for 14q was strongly correlated with the presence of 11q LOH (P < 0.001 ) and inversely correlated with MYCN amplification (P= 0.04). CONCLUSIONS: LOH for 14q was evident in all clinical risk groups, indicating that this abnormality may be a universal feature of neuroblastoma tumor development. These findings suggest that a tumor suppressor gene involved in the initiation or progression of neuroblastoma is located within distal 14q.

Child↗
PubMed2001

Detailed molecular analysis of 1p36 in neuroblastoma.

BACKGROUND: Several lines of evidence es tablish that chromosome band 1p36 is frequently deleted in neuroblastoma primary tumors and cell lines, suggesting that a tumor suppressor gene within this region is involved in the development of this tumor. PROCEDURE: We analyzed the status of 1p36 in primary neuroblastomas and cell lines to define the region of consistent rearrangement. RESULTS: Loss of heterozygosity (LOH) studies of primary neuro blastomas identified allelic loss in 135 of 503 tumors (27%), with the smallest region of overlap (SRO) defined distal to D15214 (1p36.3). No homozygous deletions were detected at 120 loci mapping to 1p36.1-p36.3 in a panel of 46 neuroblastoma cell lines. A recently identified patient with neuroblastoma was found to have a constitutional deletion within 1p36.2-p36.3, and this deletion, when combined with the LOH results, defined a smaller SRO of one megabase within 1p36.3. We constructed a comprehensive integrated map of chromosome 1 containing 11,000 markers and large-insert clones, a high-resolution radiation hybrid (RH) map of 1p36, and a P1-artificial chromosome (PAC) contig spanning the SRO, to further characterize the region of interest. Over 768 kb (75%) of the SRO has been sequenced to completion. Further analysis of distal 1p identified 113 transcripts localizing to 1p36, 21 of which were mapped within the SRO. CONCLUSION: This analysis will identify suitable positional candidate transcripts for mutational screening and subsequent identification of the 1p36.3 neuroblastoma suppressor gene.

Alleles↗
PubMed1999

A comparison of two algorithms, MultiMap and gene mapping system, for automated construction of genetic linkage maps.

Using the GAW11 Problem 2 data set, we compared the performance of two automated map construction algorithms, MultiMap and GMS (Gene Mapping System). The MultiMap algorithm iteratively adds markers in a stepwise manner to the map, while the GMS algorithm seeks to find the best order of the whole set of markers by selective permutations of logically formed subgroups of the markers. While it is difficult to compare these two rather different algorithms, we found that, on these data, GMS performed better than MultiMap, placing more markers in their true order on average, with little order ambiguity. In addition, as the number of markers increased, GMS was less computationally demanding than MultiMap. However, it MultiMap placed a marker, it was almost always in the correct order. In contrast, GMS often placed a group of markers on the wrong end of the map; such incorrect placements occur when the evidence for placement on one end or the other is not strong. Thus, there is room for further algorithmic developments that combine the strengths of both the MultiMap and GMS approaches.

Algorithms↗
PubMed1999

Power loss for multiallelic transmission/disequilibrium test when errors introduced: GAW11 simulated data.

Many researchers are considering the use of transmission/disequilibrium tests (TDT) for trios of genotypes (father, mother, child) as a method for localizing genes associated with complex diseases. We evaluate the effect of random errors (allele changes) in trios on the power to detect linkage. For a marker in the simulated data set, one allele is associated with the fictitious disease in a certain subpopulation. For the data as given (no errors), our power to detect linkage using the multiallelic TDT (TDTmhet) is 68% (critical p-value set at 0.0001). We introduce errors into trios at various rates (1%, 5%, or 10%), remove only trios displaying mendelian inconsistencies, and recalculate power to detect linkage. Our principal finding is that there is power loss to detect linkage with the TDTmhet when errors are introduced. We observe power losses of 8%, 16%, and 48% for error rates of 1%, 5%, and 10%, respectively. To determine the source of the power loss, we perform Monte Carlo simulations. At the 1% and 5% rates, we conclude that power loss is due primarily to loss in sample size. At the 10% rate, we observe substantial power loss due to error introduction in addition to sample size reduction. We also determine, given a particular error rate, the probability that we detect errors if we use only mendelian consistency as a check. We find that the mean detection rates for the data sets with 1%, 5%, or 10% error rates are 58%, 60%, and 62%, respectively. As a result, the apparent error rate appears to be almost half the true error rate. Based on these results, we recommend that researchers maintain error rates below 5% when using the TDTmhet for linkage, use additional methods beyond mendelian consistency checks when searching for errors in their data, and modify sample size calculations when accounting for errors in their genotype data.

Alleles↗
PubMed1999

A comprehensive view of human chromosome 1.

Comprehensive representations of human chromosomes combining diverse genomic data sets, localizing expressed sequences, and reflecting physical distance are essential for disease gene identification and sequencing efforts. We have developed a method (CompView) for integrating genomic information derived from available cytogenetic, genetic linkage, radiation hybrid, physical, and transcript-based mapping approaches. CompView generates chromosome representations with substantially higher resolution, coverage, and integration than current maps of the human genome. The CompView process was used to build a representation of human chromosome 1, yielding a map with >13,000 unique elements, an effective resolution of 910 kb, and a marker density of 50 kb. CompView creates comprehensive and fully integrated depictions of a chromosome's clinical, biological, and structural information.

Chromosome Mapping↗
PubMed1998

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗
PubMed1998

Genome-wide search for schizophrenia susceptibility loci: the NIMH Genetics Initiative and Millennium Consortium.

Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment.

Adolescent↗
PubMed1998

NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees.

The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article-one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample-presents results for African-American pedigrees. The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01-0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere.

Adolescent↗
PubMed1998

Age-related macular degeneration. Clinical features in a large family and linkage to chromosome 1q.

OBJECTIVES: To identify the chromosomal location of a disease-causing gene and to describe the clinical characteristics of a large family with age-related macular degeneration (ARMD). METHODS: An ARMD pedigree was identified, and the disease state of family members was documented by stereoscopic fundus photography and was classified using a modified version of the Wisconsin Age-Related Maculopathy Grading System. A genome-wide screen at approximately 6-centimorgan spacing using a DNA-pooling strategy combined with shared-segment analysis was used to identify likely chromosomal regions. The entire family was then screened at each likely locus, and 1 positive locus was refined by screening with markers at an average density of 0.5 centimorgan and subjected to parametric linkage analysis. RESULTS: In the 10 affected family members, ARMD was manifest by the presence of large, soft, confluent drusen accompanied by varying degrees of retinal pigment epithelial degeneration and/or geographic atrophy. Age-related macular degeneration segregated as an autosomal-dominant trait, with the disease locus mapping to chromosome 1q25-q31 between markers D1S466 and D1S413, with a multipoint lod score of 3.00. CONCLUSION: Age-related macular degeneration localized to chromosome 1q25-q31 (gene symbol, ARMD1) as a dominant trait in a large family with a predominantly dry phenotype. CLINICAL RELEVANCE: Identification of ARMD genes will facilitate early diagnosis and aid in understanding the molecular pathophysiological mechanisms of ARMD. This knowledge will contribute to the development of preventive and improved treatment strategies.

Aged↗
PubMed1998

An integrated genetic linkage map of the laboratory rat.

The laboratory rat, Rattus novegicus, is a major model system for physiological and pathophysiological studies, and since 1966 more than 422,000 publications describe biological studies on the rat (NCBI/Medline). The rat is becoming an increasingly important genetic model for the study of specific diseases, as well as retaining its role as a major preclinical model system for pharmaceutical development. The initial genetic linkage map of the rat contained 432 genetic markers (Jacob et al. 1995) out of 1171 developed due to the relatively low polymorphism rate of the mapping cross used (SHR x BN) when compared to the interspecific crosses in the mouse. While the rat genome project continues to localize additional markers on the linkage map, and as of 11/97 more than 3,200 loci have been mapped. Current map construction is using two different crosses (SHRSP x BN and FHH x ACI) rather than the initial mapping cross. Consequently there is a need to provide integration among the different maps. We set out to develop an integrated map, as well as increase the number of markers on the rat genetic map. The crosses available for this analysis included the original mapping cross SHR x BN reciprocal F2 intercross (448 markers), a GH x BN intercross (205 markers), a SS/Mcw x BN intercross (235 markers), and a FHH/Eur x ACI/Hsd intercross (276 markers), which is also one of the new mapping crosses. Forty-six animals from each cross were genotyped with markers polymorphic for that cross. The maps appear to cover the vast majority of the rat genome. The availability of these additional markers should facilitate more complete whole genome scans in a greater number of strains and provide additional markers in specific genomic regions of interest.

Animals↗
PubMed1997

An integrated transcript map of human chromosome 1p35-p36.

The distal short arm of human chromosome 1 (1p) is rearranged in a variety of malignancies, and several genetic diseases also map to this region. We have constructed an integrated transcript map to precisely define the positions of genes and expressed sequence tags (ESTs) previously mapped to 1p35-p36, a region spanning approximately 40 Mb. To anchor the integrated map, a framework genetic map was constructed with 24 genetic markers and a marker order of 1000:1 odds, yielding an average resolution of 2.8 cM. An additional 106 genetic markers were localized relative to the framework genetic map. To place markers more precisely within 1p35-p36, a chromosome 1-specific, radiation-reduced hybrid (RH) panel was created. Individual DNA fragments of the RH panel were identified and ordered by PCR with the framework genetic map. A total of 250 markers, including 142 genes and ESTs, were mapped by PCR against the RH panel. The map has an observed resolution of 800 kb, and the results closely match and more precisely define previous mapping information for most markers. This map will help to identify candidate genes for genetic diseases mapping to distal 1p and is fully integrated with existing genetic and RH maps of the human genome.

Animals↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗