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Biomedical subjects

M Litt

Publications and source records attributed to M Litt.

At least 55 records · Page 3Linked to original sources
PubMed1995

CEPH consortium map of chromosome 14.

Families from the linkage panel of Centre d'Etude du Polymorphisme Humain have been used to generate a linkage map containing 68 loci; 13 genes, 33 di- and 4 tetranucleotide repeats, one oligonucleotide ligation assay (OLA), and 17 RFLPs. This map integrates markers from several previous maps, and has undergone further error checking. 43 loci have been placed with odds of 1000:1 or greater, five with odds of 100:1, with an average interval of 3.5 cM. An additional 20 loci have been placed within defined intervals.

Chromosome Mapping↗
PubMed1995

A physical map of the region spanning the chromosome 12 translocation breakpoint in a mesothelioma with a t(X;12)(q22;p13).

We have constructed a physical map of a 4.6-cM region of human chromosome band 12p13.3 that contains a translocation breakpoint from a mesothelioma with a t(X;12)(q22;p13). The map contains a contig of 22 yeast artificial chromosomes (YACs), onto which we have placed 18 sequence tagged site (STS) markers, including seven genes: D12S370, FGF6, KCAN1, KCNA5, KCNA6, NTF3, and VWF. A second YAC contig, comprised of 22 YAC clones, was located distal to the mesothelioma breakpoint and contained 12 STS markers, including four genes (CACNL1A1, D12S380E, D12S381E, and D12S382E). Based on STS content and fluorescence in situ hybridization experiments, two stable, nonchimeric YAC clones were found that span the mesothelioma breakpoint. A long-range restriction map of an 800-kb region was constructed and used to refine the mesothelioma breakpoint to a region of approximately 100 kb, flanked by the potassium channel genes KCNA1 and KCNA5. The latter was confirmed by direct visual hybridization (DIRVISH) experiments, using cosmids isolated for markers flanking the breakpoint as probes.

Animals↗
PubMed1995

No evidence for association of familial Parkinson's disease with CAG repeat expansion.

In some kindreds, familial Parkinson's disease (PD) exhibits genetic anticipation. Thus, we postulated that familial PD in certain kindreds may be associated with a CAG repeat expansion. However, using the repeat expansion detection method, we found no significant increase in the frequency of CAG repeat expansion among 46 unrelated PD probands compared with controls. Nor did we find evidence for CAG repeat expansion between generations in 11 different PD families that exhibit anticipation in age at onset.

Adult↗
PubMed1994

Human genes encoding the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane: mapping and identification of two new isoforms.

The voltage-dependent anion channel of the mitochondrial outer membrane (VDAC) is a small, abundant pore-forming protein found in the outer membranes of all eukaryotic mitochondria. The VDAC protein is believed to form the major pathway for movement of adenine nucleotides through the outer membrane and to be the mitochondrial binding site for hexokinase and glycerol kinase. Previous studies have indicated that at least two human VDAC isoforms are expressed. Here, we report the mapping of VDAC1 to the X chromosome in the interval Xq13-q21 and VDAC2 to chromosome 21 by polymerase chain reaction and restriction analysis of a human/rodent somatic cell mapping panel. In the process of mapping these genes, we identified and mapped two additional sequences highly homologous to VDAC1. VDAC3 maps to chromosome 12 and VDAC4 maps to chromosome 1. The locations of VDAC1 and VDAC4 have been confirmed by fluorescence in situ hybridization analysis. Future studies will be aimed at defining the specific physiological role of each member of this family of channel proteins.

Base Sequence↗
PubMed1994

Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.

Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/myokymia can result from mutations in this gene.

Amino Acid Sequence↗
PubMed1994

Issues in the development of client-treatment matching hypotheses.

This article discusses observations and insights that were gained in the course of critiquing the a priori client-treatment matching hypothesis that were developed for Project MATCH. A matching taxonomy is offered that differentiates eight types of ordinal and disordinal interactions and discusses their clinical and substantive implications. Previously reported alcohol treatment studies are used to illustrate many of these. Various issues in matching studies, such as power versus complexity, prediction versus explanation, matches versus mismatches and capitalization versus compensation, are discussed. Selective issues in choosing treatment and client-matching variables as they affect matching hypotheses are also addressed. The importance of developing a putative "causal chain" for testing the theory underlying matching processes is explicated and a procedure for testing this causal chain is outlined.

Alcoholism↗
PubMed1994

A gene for episodic ataxia/myokymia maps to chromosome 12p13.

Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.

Chromosome Mapping↗
PubMed1994

Tightly linked flanking microsatellite markers for the Usher syndrome type I locus on the short arm of chromosome 11.

Usher syndrome type I is an autosomal recessive disease characterized by profound congenital hearing impairment and vestibular dysfunction followed by the onset of progressive pigmentary retinopathy in childhood or early adolescence. A locus (USH1C) for one form of this disease was previously assigned to the short arm of chromosome 11 through linkage studies in the Acadian population of southwestern Louisiana. Linkage analyses of a set of microsatellite markers in 27 Acadian families provide evidence that USH1C lies between D11S861 and D11S928. Three markers (D11S419, D11S921, and D11S899) that lie between the flanking markers show no recombination with USH1C, and all 54 chromosomes with the abnormal allele at the disease locus have identical alleles for D11S419 and D11S921. This haplotype was found on only 10 of 50 chromosomes with the normal allele at the disease locus, suggesting a strong founder effect. Of the 54 chromosomes with the abnormal allele, 12 had a divergent allele at D11S899. These results suggest that USH1C is in the 2-3-cM interval between D11S861 and D11S899.

Chromosomes, Human, Pair 11↗
PubMed1994

Refining the locus for Best vitelliform macular dystrophy and mutation analysis of the candidate gene ROM1.

Vitelliform macular dystrophy (Best disease) is an autosomal dominant macular dystrophy which shares important clinical features with age-related macular degeneration, the most common cause of legal blindness in the elderly. Unfortunately, our understanding and treatment for this common age-related disorder is limited. Discovery of the gene which causes Best disease has the potential to increase our understanding of the pathogenesis of all types of macular degeneration, including the common age-related form. Best disease has recently been mapped to chromosome 11q13. The photoreceptor-specific protein ROM1 has also been recently mapped to this location, and the ROM1 gene is a candidate gene for Best disease. Using highly polymorphic markers, we have narrowed the genetic region which contains the Best disease gene to the 10-cM region between markers D11S871 and PYGM. Marker D11S956 demonstrated no recombinants with Best disease in three large families and resulted in a lod score of 18.2. In addition, a polymorphism within the ROM1 gene also demonstrated no recombinants and resulted in a lod score of 10.0 in these same three families. We used a combination of SSCP analysis, denaturing gradient gel electrophoresis, and DNA sequencing to screen the entire coding region of the ROM1 gene in 11 different unrelated patients affected with Best disease. No nucleotide changes were found in the coding sequence of any affected patient, indicating that mutations within the coding sequence are unlikely to cause Best disease.

Base Sequence↗
PubMed1993

A study of the origin of 'shadow bands' seen when typing dinucleotide repeat polymorphisms by the PCR.

Dinucleotide repeat polymorphisms ('microsatellites') are usually typed by resolving the products of PCR amplification on denaturing acrylamide gels. With this methodology, an allele consists not of a single fragment, but rather of a ladder of fragments, typically separated by intervals of 2nt. Mechanisms that have been invoked to explain the generation of these 'shadow bands' include slipped strand mispairing occurring during the PCR and artefactual 'recombination' caused by out-of-register annealing of truncated PCR products. The D11S527 locus contains the microsatellite sequence (GT)n(CTGT)m. By performing direct sequencing of PCR products derived from individuals homozygous at D11S527, we show that these products vary in length due solely to variations in the length of the dinucleotide repeat tract. These results rule out PCR recombination and support slipped strand mispairing as the major mechanism for generation of shadow bands.

Alleles↗
PubMed1993

A microsatellite-based index map of human chromosome 11.

We have constructed a continuous index map of 25 microsatellite markers on human chromosome 11. The markers have been typed in 40 CEPH families, have heterozygosities of 69% or higher and can be typed by PCR. The odds against inversion of adjacent marker loci order are at least 10(5):1. The sex average map covers a total of 162 cM with no gap exceeding 15 cM. Total lengths for female and male maps are 205 and 123 cM, respectively. By use of a hybrid cell panel or by in situ hybridization, 16 of the markers have also been mapped cytogenetically, providing a good correlation of the index map with the cytogenetic map. The map will facilitate high resolution mapping of additional polymorphic loci and of disease genes on chromosome 11.

Chromosome Mapping↗
PubMed1993

Tricarboxylic acid cycle activity in postischemic rat hearts.

BACKGROUND: Although myocardial oxidative tricarboxylic acid (TCA) cycle activity and contractile function are closely linked in normal cardiac muscle, their relation during postischemic reperfusion, when contractility often is reduced, is not well defined. METHODS AND RESULTS: To test the hypothesis that oxidative TCA cycle flux is reduced in reperfused myocardium with persistent contractile dysfunction, TCA cycle flux was measured by analyzing the time course of sequential myocardial glutamate labeling during 13C-labeled substrate infusion with 13C nuclear magnetic resonance spectroscopy in beating isolated rat hearts at 37 degrees C. Total TCA cycle flux, indexed by both empirical and mathematical modeling analyses of the 13C data, was not reduced but rather increased in hearts reperfused after 17-20 minutes of ischemia (left ventricular pressure, 73 +/- 5% of preischemic values) compared with flux in developed pressure-matched controls (e.g., total flux, 2.5 +/- 0.4 versus 1.6 +/- 0.1 mumol.min-1.g wet wt-1, respectively; p < 0.01). No TCA cycle activity was detectable by 13C nuclear magnetic resonance in hearts reperfused after 40-45 minutes of ischemia, which lacked contractile recovery and had ultrastructural evidence of irreversible injury. CONCLUSIONS: These results suggest that TCA cycle activity is not persistently decreased in dysfunctional reperfused myocardium after a brief ischemic episode and therefore cannot account for the reduced contractile function at that time.

Animals↗
PubMed1993

Shadow bands seen when typing polymorphic dinucleotide repeats: some causes and cures.

Polymorphic dinucleotide repeats are generally typed by using the PCR to generate products that are resolved on denaturing acrylamide gels. The presence of "shadow bands" on these gels often makes it difficult to score alleles reliably. We have developed procedures that overcome many of these difficulties. Important aspects of these improved procedures include using gels containing formamide as well as urea, transferring the resolved allelic fragments to nylon membranes by capillary blotting and probing the membranes with locus-specific oligonucleotide probes.

Base Sequence↗