118 research outputs found
Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome.
BACKGROUND: EAST syndrome is an autosomal recessive disorder caused by loss-of-function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a result we aimed to establish the existence of a potential founder effect in the Pakistani population. METHODS: To this end, we genotyped 12 patients from seven families and we compared disease haplotypes with ethnically matched control chromosomes. This haplotype was used together with demographic data for Pakistan to estimate the age of this founder mutation. RESULTS: We identified a small homozygous 0.694 Mb region around the KCNJ10 p.R65P mutation that had identical haplotypes in all of the patients which were completely absent in the control sample. Based on current demographic data and knowledge about disease frequency, we estimate that this particular p.R65P mutation arose 20 generations (about 500 years) ago. CONCLUSION: By knowing the prevalent mutation in a given population more efficient diagnostics can be performed and the families can benefit from specific counseling
HaploForge: a comprehensive pedigree drawing and haplotype visualization web application
Motivation: Haplotype reconstruction is an important tool for understanding the aetiology of human disease. Haplotyping infers the most likely phase of observed genotypes conditional on constraints imposed by the genotypes of other pedigree members. The results of haplotype reconstruction, when visualized appropriately, show which alleles are identical by descent despite the presence of untyped individuals. When used in concert with linkage analysis, haplotyping can help delineate a locus of interest and provide a succinct explanation for the transmission of the trait locus. Unfortunately, the design choices made by existing haplotype visualization programs do not scale to large numbers of markers. Indeed, following haplotypes from generation to generation requires excessive scrolling back and forth. In addition, the most widely used program for haplotype visualization produces inconsistent recombination artefacts for the X chromosome. / Results: To resolve these issues, we developed HaploForge, a novel web application for haplotype visualization and pedigree drawing. HaploForge takes advantage of HTML5 to be fast, portable and avoid the need for local installation. It can accurately visualize autosomal and X-linked haplotypes from both outbred and consanguineous pedigrees. Haplotypes are coloured based on identity by descent using a novel A* search algorithm and we provide a flexible viewing mode to aid visual inspection. HaploForge can currently process haplotype reconstruction output from Allegro, GeneHunter, Merlin and Simwalk. / Availability and implementation: HaploForge is licensed under GPLv3 and is hosted and maintained via GitHub. https://github.com/mtekman/haploforge / Contact: [email protected] / Supplementary information: Supplementary data are available at Bioinformatics online
Electron Standing Wave Formation in Atomic Wires
Using the Landauer formulation of transport theory and tight binding models
of the electronic structure, we study electron transport through atomic wires
that form 1D constrictions between pairs of metallic nano-contacts. Our results
are interpreted in terms of electron standing waves formed in the atomic wires
due to interference of electron waves reflected at the ends of the atomic
constrictions. We explore the influence of the chemistry of the atomic
wire-metal contact interfaces on these standing waves and the associated
transport resonances by considering two types of atomic wires: gold wires
attached to gold contacts and carbon wires attached to gold contacts. We find
that the conductance of the gold wires is roughly for the
wire lengths studied, in agreement with experiments. By contrast, for the
carbon wires the conductance is found to oscillate strongly as the number of
atoms in the wire varies, the odd numbered chains being more conductive than
the even numbered ones, in agreement with previous theoretical work that was
based on a different model of the carbon wire and metal contacts.Comment: 14 pages, includes 6 figure
Effect of deconfinement on resonant transport in quantum wires
The effect of deconfinement due to finite band offsets on transport through
quantum wires with two constrictions is investigated. It is shown that the
increase in resonance linewidth becomes increasingly important as the size is
reduced and ultimately places an upper limit on the energy (temperature) scale
for which resonances may be observed.Comment: 6 pages, 6 postscript files with figures; uses REVTe
Adhesive energy, force and barrier height between simple metal surfaces
Using the self-consistent field pseudopotential method we calculated the adhesive energy, perpendicular and lateral forces and barrier height between two rigid A1(001) slabs modeling the sample and a blunt tip. We found that the adhesive energy and forces are site specific, and can lead to a significant corrugation in the constant force mode with negative force gradient. Lateral forces, which determine friction on the atomic scale are not simply proportional to the perpendicular force, and are typically one order of magnitude smaller. Our results confirm that perpendicular tip force and barrier height are interrelated for separations where the force gradient is positive. © 1992
Persistent Currents in the Presence of a Transport Current
We have considered a system of a metallic ring coupled to two electron
reservoirs. We show that in the presence of a transport current, the persistent
current can flow in a ring, even in the absence of magnetic field. This is
purely a quantum effect and is related to the current magnification in the
loop. These persistent currents can be observed if one tunes the Fermi energy
near the antiresonances of the total transmission coefficient or the two port
conductance.Comment: To appear in Phys. Rev. B. Three figures available on reques
Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD)
BACKGROUND: Polycystic kidney disease with hyperinsulinaemic hypoglycaemia (HIPKD) is a recently described disease caused by a single nucleotide variant, c.-167G>T, in the promoter region of PMM2 (encoding phosphomannomutase 2), either in homozygosity or compound heterozygosity with a pathogenic coding variant in trans. All patients identified so far are of European descent, suggesting a possible founder effect. METHODS: We generated high density genotyping data from 11 patients from seven unrelated families, and used this information to identify a common haplotype that included the promoter variant. We estimated the age of the promoter mutation with DMLE+ software, using demographic parameters corresponding to the European population. RESULTS: All patients shared a 0.312 Mb haplotype which was absent in 503 European controls available in the 1000 Genomes Project. The age of this mutation was estimated as 105-110 generations, indicating its occurrence around 600 BC, a time of intense migration, which might explain the presence of the same mutations in Europeans around the globe. CONCLUSION: The shared unique haplotype among seemingly unrelated patients is consistent with a founder effect in Europeans
Kondo effect in side coupled double quantum-dot molecule
Electron tunneling through a double quantum dot molecule side attached to a
quantum wire, in the Kondo regime, is studied. The mean-field finite-U
slave-boson formalism is used to obtain the solution of the problem. We found
conductance cancelations when the molecular energies of the side attached
double quantum-dot cross the Fermi energy. We investigate the many body
molecular Kondo states as a function of the parameters of the system.Comment: 12 pages, 7 figures. Submitted to Solid State Com
Quantum heat transfer through an atomic wire
We studied the phononic heat transfer through an atomic dielectric wire with
both infinite and finite lengths by using a model Hamiltonian approach. At low
temperature under ballistic transport, the thermal conductance contributed by
each phonon branch of a uniform and harmonic chain cannot exceed the well-known
value which depends linearly on temperature but is material independent. We
predict that this ballistic thermal conductance will exhibit stepwise behavior
as a function of temperature. By performing numerical calculations on a more
realistic system, where a small atomic chain is placed between two reservoirs,
we also found resonance modes, which should also lead to the stepwise behavior
in the thermal conductance.Comment: 14 pages, 2 separate figure
Quantum point contact on graphite surface
The conductance through a quantum point contact created by a sharp and hard
metal tip on the graphite surface has features which to our knowledge have not
been encountered so far in metal contacts or in nanowires. In this paper we
first investigate these features which emerge from the strongly directional
bonding and electronic structure of graphite, and provide a theoretical
understanding for the electronic conduction through quantum point contacts. Our
study involves the molecular-dynamics simulations to reveal the variation of
interlayer distances and atomic structure at the proximity of the contact that
evolves by the tip pressing toward the surface. The effects of the elastic
deformation on the electronic structure, state density at the Fermi level, and
crystal potential are analyzed by performing self-consistent-field
pseudopotential calculations within the local-density approximation. It is
found that the metallicity of graphite increases under the uniaxial compressive
strain perpendicular to the basal plane. The quantum point contact is modeled
by a constriction with a realistic potential. The conductance is calculated by
representing the current transporting states in Laue representation, and the
variation of conductance with the evolution of contact is explained by taking
the characteristic features of graphite into account. It is shown that the
sequential puncturing of the layers characterizes the conductance.Comment: LaTeX, 11 pages, 9 figures (included), to be published in Phys. Rev.
B, tentatively scheduled for 15 September 1998 (Volume 58, Number 12
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