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M Kaplan HJ Vreman C Hammerman C Leiter B Rudensky MG MacDonald DK Stevenson 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(4):455-457
The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia. 相似文献
4.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
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The large-scale structure of chromatin corresponding to G- and R-bands in human G0/G1 interphase nuclei was compared. Fluorescence in situ hybridization (FISH) was used to measure the interphase distance between 42 pairs of probes separated by 0.1–1.5Mbp. The probe pairs were derived from 21q22.2 and Xp21.3, G-band positive regions, and from 4p16.3, 6p21.3, and Xq28, R-band positive regions. Distributions of measured interphase distances in all regions approximated a Rayleigh distribution, suggesting that the chromatin follows a random-walk path over this range. A linear correlation of mean-square interphase distance and genomic separation, also indicative of random-walk folding, was observed in all regions. The slope of the correlation observed using probes from G-band regions was systematically lower than that from R-band regions. The difference in the slope between Xp21.3 and Xq28 was particularly striking and was observed in normal fibroblast cells, fixed alternatively with methanol and acetic acid or paraformaldehyde, and HeLa cells. These results demonstrate regional differences in large-scale chromosome structure during interphase, with the more openly configured chromatin corresponding to R-bands.This revised version was published online in November 2005 with corrections to the Cover Date. 相似文献
6.
Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ~100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans. 相似文献
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The BAC-end sequencing, or sequence-tagged-connector (STC), approach to genome sequencing involves sequencing the ends of BAC inserts to scatter sequence tags (STCs) randomly across the genome. Once any BAC or other large segment of DNA is sequenced to completion by conventional shotgun approaches, these STC tags can be used to identify a minimum tiling path of BAC clones overlapping the nucleation sequence for sequence extension. Here, we explore the properties of STC-sequencing strategies within a mathematical model of a random target with homologous repeats and imperfect sequencing technology to understand the consequences of varying various parameters on the incidence of problem clones and the cost of the sequencing project. Problem clones are defined as clones for which either (A) there is no identifiable overlapping STC to extend the sequence in a particular direction or (B) the identified STC with minimum overlap comes from a nonoverlapping clone, either owing to random false matches or repeat-family homology. Based on the minimum overlap, we estimate the number of clones to be entirely sequenced and, then, using cost estimates, identify the decision rule (the degree of sequence similarity required before a match is declared between an STC and a clone) to minimize overall sequencing cost. A method to optimize the overlap decision rule is highly desirable, because both the total cost and the number of problem clones are shown to be highly sensitive to this choice. For a target of 3 Gb containing approximately 800 Mb of repeats with 85%-90% identity, we expect <10 problem clones with 15 times coverage by 150-kb clones. We derive the optimal redundancy and insert sizes of clone libraries for sequencing genomes of various sizes, from microbial to human. We estimate that establishing the resource of STCs as a means of identifying minimally overlapping clones represents only 1%-3% of the total cost of sequencing the human genome, and, up to a point of diminishing returns, a larger STC resource is associated with a smaller total sequencing cost. 相似文献
9.
Inhibition of phase separation by reagents that prevent X-irradiation cataract in vivo 总被引:1,自引:0,他引:1
Galactose, and the phosphorothioates, WR-77913 and WR-2721, which inhibit cataract produced by X-irradiation, were evaluated for their effects on the phase separation temperature, Tc, of calf lens homogenate. The reagents were added to nuclear homogenate and the change in Tc per mol, dTc/dC, was measured. Galactose decreased Tc, -65 degrees C mol-1, WR-77913 decreased Tc, -28 degrees C mol-1 and WR-2721 decreased Tc, -76 degrees C mol-1. These are the first phase separation inhibitors that can be used in vivo to study the inhibition of lens opacification. 相似文献
10.
Darrin J. Trask William R. Ledoux Eric C. Whittaker Grant C. Roush Bruce J. Sangeorzan 《Journal of orthopaedic research》2014,32(3):385-393
Symptom relief of recalcitrant metatarsalgia can be achieved through surgical shortening of the affected metatarsal, thus decreasing plantar pressure. Theoretically an oblique metatarsal osteotomy can be oriented distal to proximal (DP) or proximal to distal (PD). We characterized the relationship between the amount of second metatarsal shortening, osteotomy plane, and plantar pressure. We hypothesized that the PD osteotomy is more effective in reducing metatarsal peak pressure and pressure time integral. We performed eight DP and eight PD second metatarsal osteotomies on eight pairs of cadaveric feet. A custom designed robotic gait simulator (RGS) generated dynamic in vitro simulations of gait. Second metatarsals were incrementally shortened, with three trials for each length. We calculated regression lines for peak pressure and pressure time integral vs. metatarsal shortening. Shortening the second metatarsal using either osteotomy significantly affected the metatarsal peak pressure and pressure time integral (first and third metatarsal increased, p < 0.01 and <0.05; second metatarsal decreased, p < 0.01). Changes in peak pressure (p = 0.0019) and pressure time integral (p = 0.0046) were more sensitive to second metatarsal shortening with the PD osteotomy than the DP osteotomy. The PD osteotomy plane reduces plantar pressure more effectively than the DP osteotomy plane. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 32:385–393, 2014. 相似文献