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71.
Linkage of Niemann-Pick disease type D to the same region of human chromosome 18 as Niemann-Pick disease type C. 总被引:1,自引:0,他引:1 下载免费PDF全文
W L Greer D C Riddell D M Byers J P Welch G S Girouard S M Sparrow T L Gillan P E Neumann 《American journal of human genetics》1997,61(1):139-142
Niemann-Pick type II disease is a severe disorder characterized by accumulation of tissue cholesterol and sphingomyelin and by progressive degeneration of the nervous system. This disease has two clinically similar subtypes, type C (NPC) and type D (NPD). NPC is clinically variable and has been identified in many ethnic groups. NPD, on the other hand, has been reported only in descendants of an Acadian couple who lived in Nova Scotia in the early 18th century and has a more homogeneous expression resembling that of less severely affected NPC patients. Despite biochemical differences, it has not been established whether NPC and NPD are allelic variants of the same disease. We report here that NPD is tightly linked (recombination fraction .00; maximum LOD score 4.50) to a microsatellite marker, D18S480, from the centromeric region of chromosome 18q. Carstea et al. have reported that the NPC gene maps to this same site; therefore we suggest that NPC and NPD likely result from mutations in the same gene. 相似文献
72.
73.
The murid rodent subfamily Sigmodontinae contains 79 genera which are
distributed throughout the New World. The time of arrival of the first
sigmodontines in South America and the estimated divergence time(s) of the
different lineages of South American sigmodontines have been controversial
due to the lack of a good fossil record and the immense number of extant
species. The "early-arrival hypothesis" states that the sigmodontines must
have arrived in South America no later than the early Miocene, at least 20
MYA, in order to account for their vast present-day diversity, whereas the
"late-arrival hypothesis" includes the sigmodontines as part of the
Plio-Pleistocene Great American Interchange, which occurred approximately
3.5 MYA. The phylogenetic relationships among 33 of these genera were
reconstructed using mitochondrial DNA (mtDNA) sequence data from the ND3,
ND4L, arginine tRNA, and ND4 genes, which we show to be evolving at the
same rate. A molecular clock was calibrated for these genes using published
fossil dates, and the genetic distances were estimated from the DNA
sequences in this study. The molecular clock was used to estimate the dates
of the South American sigmodontine origin and the main sigmodontine
radiation in order to evaluate the "early-" and "late-arrival" scenarios.
We estimate the time of the sigmodontine invasion of South America as
between approximately 5 and 9 MYA, supporting neither of the scenarios but
suggesting two possible models in which the invading lineage was either (1)
ancestral to the oryzomyines, akodonts, and phyllotines or (2) ancestral to
the akodonts and phyllotines and accompanied by the oryzomyines. The
sigmodontine invasion of South America provides an example of the advantage
afforded to a lineage by the fortuitous invasion of a previously
unexploited habitat, in this case an entire continent.
相似文献
74.
James Riddell 《BMJ (Clinical research ed.)》1936,1(3928):792-793
75.
Oswaldo Keith Okamoto Ana Carolina SR Carvalho Luciana C Marti Ricardo Z Vêncio Carlos A Moreira-Filho 《Cancer cell international》2007,7(1):11
Background
Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell expansion and tumor development should facilitate the identification of novel therapeutic targets in cancer. 相似文献76.
Kloverpris HN Stryhn A Harndahl M van der Stok M Payne RP Matthews PC Chen F Riddell L Walker BD Ndung'u T Buus S Goulder P 《Journal of virology》2012,86(2):919-929
The genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B*57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B*57 alleles and the closely related HLA-B*5801 are often grouped together because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B*57 alleles, termed HLA-B*57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C-clade-infected subjects from southern Africa, HLA-B*5703 is associated with a lower viral-load set point than HLA-B*5702 and HLA-B*5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma; P = 0.24 and P = 0.0005). In order to better understand these observed differences in HLA-B*57/5801-mediated immune control of HIV, we undertook, in a study of >1,000 C-clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both by unique CD8(+) T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8(+) T-cell responses and immune selection pressures for which these protective alleles are responsible. These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8(+) T-cell responses generated that can drive significant selection pressure on the virus. 相似文献
77.
Jun Pu Anthony F. Kreft Suzan H. Aschmies Kevin P. Atchison Joshua Berkowitz Thomas J. Caggiano Micheal Chlenov George Diamantidis Boyd L. Harrison Yun Hu Donna Huryn J. Steven Jacobsen Mei Jin Kerri Lipinski Peimin Lu Robert L. Martone Koi Morris June Sonnenberg-Reines Dave R. Riddell Joan Sabalski Lynn Resnick 《Bioorganic & medicinal chemistry》2009,17(13):4708-4717
γ-Secretase inhibitors have been shown to reduce the production of β-amyloid, a component of the plaques that are found in brains of patients with Alzheimer’s disease. A novel series of heterocyclic sulfonamide γ-secretase inhibitors that reduce β-amyloid levels in cells is reported. Several examples of compounds within this series demonstrate a higher propensity to inhibit the processing of amyloid precursor protein compared to Notch, an alternative γ-secretase substrate. 相似文献
78.
The objective was to determine the average amount of bovine viral diarrhea virus (BVDV) associated with single in vivo-derived and in vitro-produced bovine embryos following recommended processing procedures for embryos. In vivo-derived and in vitro-produced bovine embryos at 7 d post-fertilization were exposed (for 2 h) to 2 × 105-7 cell culture infective dose (CCID50)/mL of SD-1 (a noncytopathic, Type 1a strain of BVDV), and then washed according to International Embryo Transfer Society (IETS) guidelines prior to testing. Of the 87 in vivo-derived embryos tested, 27% were positive for virus by quantitative polymerase chain reaction (qPCR). The range in amount of virus associated with 99% of the contaminated embryos was ≤6.62 ± 1.57 copies/5 μL; 90% of the contaminated embryos had ≤4.64 ± 1.57 viral copies/5 μL of embryo-associated virus, using tolerance intervals (P < 0.05). The SEM was 0.33 and the mean of averages was 1.12/5 μL. Of the 87 in vitro-produced embryos, 42% were positive for virus. The range in amount of virus associated with 99% of the contaminated embryos was ≤3.44 ± 0.89 copies/5 μL; 90% of the contaminated embryos had ≤2.40 ± 0.89 viral copies/5 μL of embryo-associated virus using tolerance intervals (P < 0.05; S.E.M. was 0.14 and the mean of averages was 0.55/5 μL). Therefore, although many embryos were positive for virus, there were limited numbers of copies, thereby posing doubt regarding their potential for contamination following embryo transfer. 相似文献
79.
Dawei Jiang Peter P Jones Darryl R Davis Robert Gow Martin S Green David H Birnie SR Wayne Chen Michael H Gollob 《Channels (Austin, Tex.)》2010,4(4):302-310
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects. It is primarily caused by mutations in the cardiac ryanodine receptor (RyR2). The mechanism by which these mutations cause arrhythmia remains controversial, with discrepant findings related to the role of the RyR2 binding protein FKBP12.6. The purpose of this study was to characterize a novel RyR2 mutation identified in a kindred with clinically diagnosed CPVT.Single-strand conformational polymorphism analysis and direct DNA sequencing were used to screen the RyR2 gene for mutations. Site-directed mutagenesis was employed to introduce the mutation into the mouse RyR2 cDNA. The impact of the mutation on the interaction between RyR2 and a 12.6 kDa FK506 binding protein (FKBP12.6) was determined by immunoprecipitation and immunoblotting and its effect on RyR2 function was characterized by single cell Ca2+ imaging and [3H]ryanodine binding.A novel CPVT mutation, E189D, was identified. The E189D mutation does not alter the affinity of the channel for FKBP12.6, but it increases the propensity for store-overload-induced Ca2+ release (SOICR). Furthermore, the E189D mutation enhances the basal channel activity of RyR2 and its sensitivity to activation by caffeine.The E189D RyR2 mutation is causative for CPVT and functionally increases the propensity for SOICR without altering the affinity for FKBP12.6. These observations strengthen the notion that enhanced SOICR, but not altered FKBP12.6 binding, is a common mechanism by which RyR2 mutations cause arrhythmias.Key words: arrhythmia, calcium, death sudden, genetics, ion channels 相似文献
80.
The Stomach, Helicobacter pylori, and Acid Secretion 总被引:1,自引:0,他引:1