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Critical Interval (critical + interval)

Distribution by Scientific Domains
Life Sciences66%

Selected Abstracts

Giant Axonal Neuropathy Locus Refinement To A < 590 KB Critical Interval

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001
L Cavalier
Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder, characterised clinically by the development of chronic distal polyneuropathy during childhood, mental retardation, kinky or curly hair, skeletal abnormalities and, ultrastructurally, by axons in the central and peripheral nervous systems distended by masses of tightly woven neurofilaments. We recently localised the CAN locus in 16q24.1 to a 5-cM interval between the D16S507 and D16S511 markers by homozygosity mapping in three consanguineous Tunisian families. We have now established a contig-based physical map of the region comprising YACs and BACs where we have placed four genes, ten ESTs, three STSs and two additional microsatellite markers, and where we have identified six new SSCP polymorphisms and six new microsatellite markers. Using these markers, we have refined the position of our previous flanking recombinants. We also identified a shared haplotype between two Tunisian families and a small region of homozygosity in a Turkish family with distant consanguinity, both suggesting the occurrence of historic recombinations and supporting the conclusions based on the phase-known recombinations. Taken together, these results allow us to establish a transcription map of the region, and to narrow down the GAN position to a < 590 kb critical interval, an important step toward the identification of the defective gene. [source]

Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heart

ACTA PHYSIOLOGICA, Issue 4 2009
O. E. Osadchii
Abstract Aim:, Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia-induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea-pig heart preparations. Methods:, Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume-conducted electrocardiogram (ECG) during steady-state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Results:, Hypokalaemic perfusion (2.5 mm K+ for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re-excitation. Hypokalaemia increased the RV-to-LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD90 and refractoriness across the LV wall. As determined by local activation time recordings, the LV-to-RV transepicardial conduction and the LV transmural (epicardial-to-endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. Conclusion:, These findings suggest that hypokalaemia-induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re-excitation, amplified RV-to-LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea-pig heart. [source]

Giant Axonal Neuropathy Locus Refinement To A < 590 KB Critical Interval

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001
L Cavalier
Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder, characterised clinically by the development of chronic distal polyneuropathy during childhood, mental retardation, kinky or curly hair, skeletal abnormalities and, ultrastructurally, by axons in the central and peripheral nervous systems distended by masses of tightly woven neurofilaments. We recently localised the CAN locus in 16q24.1 to a 5-cM interval between the D16S507 and D16S511 markers by homozygosity mapping in three consanguineous Tunisian families. We have now established a contig-based physical map of the region comprising YACs and BACs where we have placed four genes, ten ESTs, three STSs and two additional microsatellite markers, and where we have identified six new SSCP polymorphisms and six new microsatellite markers. Using these markers, we have refined the position of our previous flanking recombinants. We also identified a shared haplotype between two Tunisian families and a small region of homozygosity in a Turkish family with distant consanguinity, both suggesting the occurrence of historic recombinations and supporting the conclusions based on the phase-known recombinations. Taken together, these results allow us to establish a transcription map of the region, and to narrow down the GAN position to a < 590 kb critical interval, an important step toward the identification of the defective gene. [source]

A 2.5-Mb contig constructed from Angus, Longhorn and horned Hereford DNA spanning the polled interval on bovine chromosome 1

ANIMAL GENETICS, Issue 6 2006
K. R. Wunderlich
Summary The polled locus has been mapped by genetic linkage analysis to the proximal region of bovine chromosome 1. As an intermediate step in our efforts to identify the polled locus and the underlying causative mutation for the polled phenotype, we have constructed a BAC-based physical map of the interval containing the polled locus. Clones containing genes and markers in the critical interval were isolated from the TAMBT (constructed from Angus and Longhorn genomic DNA) and CHORI-240 (constructed from horned Hereford genomic DNA) BAC libraries and ordered based on fingerprinting and the presence or absence of 80 STS markers. A single contig spanning 2.5 Mb was assembled. Comparison of the physical order of STSs to the corresponding region of human chromosome 21 revealed the same order of genes within the polled critical interval. This contig of overlapping BAC clones from horned and polled breeds is a useful resource for SNP discovery and characterization of positional candidate genes. [source]

Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heart

ACTA PHYSIOLOGICA, Issue 4 2009
O. E. Osadchii
Abstract Aim:, Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia-induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea-pig heart preparations. Methods:, Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume-conducted electrocardiogram (ECG) during steady-state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Results:, Hypokalaemic perfusion (2.5 mm K+ for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re-excitation. Hypokalaemia increased the RV-to-LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD90 and refractoriness across the LV wall. As determined by local activation time recordings, the LV-to-RV transepicardial conduction and the LV transmural (epicardial-to-endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. Conclusion:, These findings suggest that hypokalaemia-induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re-excitation, amplified RV-to-LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea-pig heart. [source]