Evidence of gene conversion in the evolutionary process of the codon 41/42 (-CTTT) mutation causing beta-thalassemia in southern China

The 4-bp deletion (-CTTT) at codon 41/42 (CD41/42) of the human beta-globin gene represents one of the most common beta-thalassemia mutations in East Asia and Southeast Asia, which is historically afflicted with endemic malaria, thus hypothetically evolvi

Mutation analysis of a large Chinese pedigree with congenital preaxial polydactyly

Mutations in the long-range limb-specific cis-regulator (ZRS) could cause ectopic shh gene expression and are responsible for preaxial polydactyly (PPD). In this study, we analyzed a large Chinese isolated autosomal dominant PPD pedigree. By fine mapping

Mitochondrial DNA Haplogroups M7b1 ' 2 and M8a Affect Clinical Expression of Leber Hereditary Optic Neuropathy in Chinese Families with the m.11778G -> A Mutation

Leber hereditary optic neuropathy (LHON) is the most extensively studied mitochondrial disease, with the majority of the cases being caused by one of three primary mitochondrial DNA (mtDNA) mutations. Incomplete disease penetrance and gender bias are two

Phantom mutation hotspots in human mitochondrial DNA

Phantom mutations are systematic artifacts generated in the course of the sequencing process. Contra common belief these artificial mutations are nearly ubiquitous in sequencing results, albeit at frequencies that may vary dramatically. The amount of artifacts depends not only on the sort of automated sequencer and sequencing chemistry employed, but also on other lab-specific factors. An experimental study executed on four samples under various combinations of sequencing conditions revealed a number of phantom mutations occurring at the same sites of mitochondrial DNA (mtDNA) repeatedly. To confirm these and identify further hotspots for artifacts, > 5000 mtDNA electropherograms were screened for artificial patterns. Further, > 30000 published hypervariable segment 1 sequences were compared at potential hotspots for phantom mutations, especially for variation at positions 16085 and 16197. Resequencing of several samples confirmed the artificial nature of these and other polymorphisms in the original publications. Single-strand sequencing, as typically executed in medical and anthropological studies, is thus highly vulnerable to this kind of artifacts. In particular, phantom mutation hotspots could easily lead to misidentification of somatic mutations and to misinterpretations in all kinds of clinical mtDNA studies.

Methylation and gene mutation in eukaryotic DNA

5-methylcytosine (m(5)C) as a rare base exists in eukaryotic genomes, which is a normal constitution in many eukaryotic DNA and the existence of m(5)C is a feature of eukaryotic DNA. Under regular physiological conditions, cytosine of eukaryotic DNA is usually methylated. Up to the present, many people consider that the m(5)C may be mutation hotspots by the deamination leading to gene mutation. Our study indicated that the spontaneous mutation caused by the transition of G.C --> A.T, in eukaryotic DNA, may result from the tautomer changing of base pairs and may also be cause by other factor actions, however it could not be caused by the deamination of m(5)C.

mtDNA haplogroup distribution in Chinese patients with Leber's hereditary optic neuropathy and G11778A mutation

Mitochondrial DNA background has been shown to be involved in the penetrance of Leber's hereditary optic neuropathy (LHON) in western Eurasian populations. To analyze mtDNA haplogroup distribution pattern in Han Chinese patients with LHON and G11778A muta

The brave new era of human genetic testing

The commercialization of 'big science' is in full swing, leading to situations in which the ethical principles of academia are beginning to be compromised. This is exemplified by the profitable business of genetic ancestry testing. The goals of this sort

Mitochondrial DNA mutation m.3635G > A may be associated with Leber hereditary optic neuropathy in Chinese

Leber hereditary optic neuropathy (LHON) was the first disease to be linked to the presence of a mitochondrial DNA (mtDNA) mutation. Nowadays over 95% of LHON cases are known to be caused by one of three primary mutations (m.11778G>A, m.14484T>C, and m.34

Gene mapping of a new coat mutation in mouse

Gene mapping of a mouse coat mutation has been investigated. First, 100 10-bp random primers were used to amplify DNA, but the mutation could not be located by this method because there were no correlation between the amplified products and coat phenotypes. Second, by using Idh1, Car2, Mup1, Pgb1, Hbb, Es10, Es1, Mod1, Gdc1, Ce2, Es3 as genetic markers, linkage test crosses (two-point test) consisting of intercrossing uncovered BALB/c mice (homozygotes) to CBA/N and C57BL/6 mice with normal hair and backcrossing the heterozygotes of the F1 to the uncovered BALB/c mice were made. It was soon evident that the mutation was linked to Es3 on chromosome 11. Furthermore, three-point test was made by using Es3 and D11Mit8 (a microsatellite DNA) as genetic markers. The result showed that the mutation was linked to Es3 with the percentage recombination of (7.89 +/- 2.19)%, and linked to D11Mit8 with the percentage recombination of (26.38 +/- 3.57)%. The percentage recombination between Es3 and D11Mit8 was (32.90 +/- 3.81)%. The mutation was named Uncovered, with the symbol Uncv. According to the recombinations, the loci order was D11Mit8-26.30 +/- 3.57- Uncv-7.89 +/- 2.19-Es3. From the location on the chromosome, it was concluded that the mutation was a new mutation which affected the skin and hair structure of mouse. The Uncv has entered MGD (Mouse Genome Database).

Complex mutation at a microsatellite locus in sturgeons: Acipenser sinensis, A-schrenckii, A-gueldenstaedtii and A-baerii

Cross-species amplifications of microsatellite locus Spl-106, which was originally screened from the genome of shovelnose sturgeon (Scaphirhynchus platorynchus) with a perfect TAGA repeat motif, were carried out in four other species of the genera Acipenser. A total of 34 polymerase chain reaction (PCR) products representing 16 different alleles of this locus was sequenced. Sequence analysis results showed that besides the number changes of repeat units, many mutational events, such as single-base substitutions and various insertion/deletion (indels) occurred not only at species level but also at individual level, even among the different alleles within the same individual. The repeat motifs varied from perfect (TAGA)n array to perfect compound (TAAA)m (GAAA)n and perfect or imperfect compound (TAAA)m (TAGA)n (TAAA)x arrays in different species and different individuals. The evolution dynamics of this locus in sturgeons was inferred in that it may evolve from a single perfect to different perfect or imperfect compounds.

Testing the relationships of Chinese freshwater Unionidae (bivalvia) based on analysis of partial mitochondrial 16s rRNA sequences

This study presents partial mitochondrial 16S rRNA sequences of 13 unionid bivalve species from China and analyses their relationships in combination with known data of 21 American mussels. According to our results, Chinese unionids, formerly regarded as two subfamilies, should be divided into three subfamilies: Ambleminae, Anodontinae and Unioninae. The genera Hyriopsis, Solenaia, Lamprotula and Ptychorhynchus, hitherto placed in Unioninae or Anodontinae, should be moved to the subfamily Ambleminae, demonstrated for the first time from China. The other genera recorded from China are suggested to belong to Anodontinae and Unioninae, which is in agreement with traditional classifications, except for the genus Lepidodesma.

Bulge testing and fracture properties of plasma-enhanced chemical vapor deposited silicon nitride thin films

The mechanical properties and fracture behavior of silicon nitride (SiNx) thin film fabricated by plasma-enhanced chemical vapor deposition is reported. Plane-strain moduli, prestresses, and fracture strengths of silicon nitride thin film; deposited both oil a bare Si substrate and oil a thermally oxidized Si substrate were extracted using bulge testing combined with a refined load-deflection model of long rectangular membranes. The plane-strain modu i and prestresses of SiNx thin films have little dependence on the substrates, that is, for the bare Si substrate, they are 133 +/- 19 GPa and 178 +/- 22 MPa, respectively, while for the thermally oxidized substrate, they are 140 +/- 26 Gila and 194 +/- 34 MPa, respectively. However, the fracture strength values of SiNx films grown on the two substrates are quite different, i.e., 1.53 +/- 0.33 Gila and 3.08 +/- 0.79 GPa for the bare Si substrate a A the oxidized Si substrate, respectively. The reference stresses were computed by integrating the local stress of the membrane at the fracture over the edge, Surface, and volume of the specimens and fitted with the Weibull distribution function. For SiNx thin film produced oil the bare Si Substrate, the Volume integration gave a significantly better agreement between data and model, implying that the volume flaws re the dominant fracture origin. For SiNx thin film grown on the oxidized Si substrate, the fit quality of surface and edge integration was significantly better than the Volume integration, and the dominant surface and edge flaws could be caused by buffered HF attacking the SiNx layer during SiO2 removal. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.

Electron beam and laser testing on the novel stripixel detectors

The novel Si stripixel detector, developed at BNL (Brookhaven National Laboratory), has been applied in the development of a prototype Si strip detector system for the PHENIX Upgrade at RHIC. The Si stripixel detector can generate X-Y two-dimensional (2D) position sensitivity with single-sided processing and readout. Test stripixel detectors with pitches of 85 and 560 mu m have been subjected to the electron beam test in a SEM set-up, and to the laser beam test in a lab test fixture with an X-Y-Z table for laser scanning. Test results have shown that the X and Y strips are well isolated from each other, and 2D position sensitivity has been well demonstrated in the novel stripixel detectors. (c) 2005 Elsevier B.V. All rights reserved.

Design, simulation and testing of large area silicon drift detectors and detector array for X-ray spectroscopy

Large area (25 mm(2)) silicon drift detectors and detector arrays (5x5) have been designed, simulated, and fabricated for X-ray spectroscopy. On the anode side, the hexagonal drift detector was designed with self-biasing spiral cathode rings (p(+)) of fixed resistance between rings and with a grounded guard anode to separate surface current from the anode current. Two designs have been used for the P-side: symmetric self-biasing spiral cathode rings (p(+)) and a uniform backside p(+) implant. Only 3 to 5 electrodes are needed to bias the detector plus an anode for signal collection. With graded electrical potential, a sub-nanoamper anode current, and a very small anode capacitance, an initial FWHM of 1.3 keV, without optimization of all parameters, has been obtained for 5.9 keV Fe-55 X-ray at RT using a uniform backside detector.