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991.
Advances in sequencing and genotyping technologies over the last decade have enabled geneticists to easily characterize genetic variation at the nucleotide level. Hundreds of genes harboring mutations associated with genetic disease have now been identified by positional cloning. Using variation at closely linked genetic markers, it is possible to predict the times in the past at which particular mutations arose. Such studies suggest that many of the rare mutations underlying human genetic disorders are relatively young. Studies of variation at genetic markers linked to particular mutations can provide insights into human geographic history, and historical patterns of natural selection and disease, that are not available from other sources. We review two approaches for estimating allele age using variation at linked genetic markers. A phylogenetic approach aims to reconstruct the gene tree underlying a sample of chromosomes carrying a particular mutation, obtaining a “direct” estimate of allele age from the age of the root of this tree. A population genetic approach relies on models of demography, mutation, and/or recombination to estimate allele age without explicitly reconstructing the gene tree. Phylogenetic methods are best suited for studies of ancient mutations, while population genetic methods are better suited for studies of recent mutations. Methods that rely on recombination to infer the ages of alleles can be fine‐tuned by choosing linked markers at optimal map distances to maximize the information available about allele age. A limitation of methods that rely on recombination is the frequent lack of a fine‐scale linkage map. Maximum likelihood and Bayesian methods for estimating allele age that rely on intensive numerical computation are described, as well as “composite” likelihood and moment‐based methods that lead to simple estimators. The former provide more accurate estimates (particularly for large samples of chromosomes) and should be employed if computationally practical. Hum Mutat 18:87–100, 2001. © 2001 Wiley‐Liss, Inc. 相似文献
992.
Masahiro Yamashita Anat Achiron Tomoyuki Miura Jun Takehisa Eiji Ido Tatsuhiko Igarashi Kentaro Ibuki Mitsuhiro Osame Shunro Sonoda Eldad Melamed Prof. Masanori Hayami Batya Shohat 《Virus genes》1995,10(1):85-90
A new endemic focus of human T-lymphotropic virus type I (HTL V-I) was recently reported among Mashhadi Jews, a group of immigrants from northeastern Iran to Israel. We extracted DNAs from fresh peripheral blood mononuclear cells (PBMCs) and/or gargle mouthwash from 10 HTL V-I carriers, who consisted of members of one family, and HTL V-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL) patients. Long terminal repeat (LTR) regions of proviral DNAs were sequenced and analyzed phylogenetically. In a phylogenetic tree, all the Mashhadi HTL V-I isolates belonged to subtype A, one of the three subtypes of the cosmopolitan type of HTL V-I, and made a tight cluster distinct from the other isolates of subtype A from Japan, India, the Caribbean Basin, and South America. Although a few nucleotide substitutions were observed among the clones sequenced, no characteristic sequence variation was found in different disease manifestations, even in one family or different sources of DNA preparation. 相似文献
993.
B. Bromm R. -D. Treede 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1987,67(1):153-162
Summary Brief radiant heat pulses, generated by a CO2 laser, were used to activate slowly conducting afferents in the hairy skin in man. In order to isolate C-fibre responses a preferential A-fibre block was applied by pressure to the radial nerve at the wrist. Stimulus estimation and evoked cerebral potentials (EP), as well as reaction times, motor and sudomotor activity were recorded in response to each stimulus. With intact nerve, the single supra-threshold stimulus induced a double pain sensation: A first sharp and stinging component (mean reaction time 480 ms) was followed by a second burning component lasting for seconds (mean reaction time 1350 ms). Under A-fibre block only one sensation remained with characteristics and latencies of second pain. The heat pulse evoked potential consisted of a late vertex negativity at 240 ms (N240) followed by a prominent late positive peak at 370 ms (P370). Later activity was not reliably present. Under A-fibre block this late EP was replaced by an ultralate EP beyond 1000 ms, which in the conventional average looked like a slow halfwave of 800 ms duration. This potential was distinct from eye movements, skin potentials or muscle artefacts. With cross-correlation methods waveforms similar to the N240/P370 were detected in the latency range from 900 to 1500 ms during A-fibre block, indicating a much greater latency jitter of the ultralate EP. Latency corrected averaging with a modified Woody filter yielded a grand mean ultralate EP (N1050/P1250), the shape of which was surprisingly similar to the late EP (N240/P370). The similarity of these components indicates that both EPs may be secondary responses to afferent input into neural centers, onto which myelinated and unmyelinated fibres converge. Such convergence may also explain through the known mechanisms of short term habituation and selective attention, why ultralate EPs are not reliably present without peripheral nerve block. 相似文献
994.
Summary The phenotypic trait starry colony in Saccharomyces is associated with a high spontaneous rho
–
petite mutability. Genetic analysis of this trait has shown the high rho
– mutability to be caused by several modifying genes present together in the strains studied. Every single modifying gene produces only a relatively small enhancement of the rho
– mutability. 相似文献
995.
SAGE是集多功能于一体的医学遗传学群体与家系资料计算机分析系统。本文概述SAGE系统的主要功能及应用环境。重点介绍了FCOR2和TDTEX两个功能模块的数学原理和使用方法。应用TDTEX模块 ,我们发现微卫星标记 85ca与小儿失神症存在连锁不平衡 ,提示在该位点附近存在小儿失神症的易感基因 相似文献
996.
Angel González-Sistal M.D. Ph.D. Alicia Baltasar Sánchez M.D. 《Journal of digital imaging》2006,19(3):270-275
Purpose This study was conducted to evaluate the diagnostic usefulness of gray level parameters in order to distinguish healthy bone
from osteoblastic metastases on digitized radiographs.
Materials and methods Skeletal radiographs of healthy bone (n = 144) and osteoblastic metastases (n = 35) were digitized using pixels 0.175 mm in size and 4,096 gray levels. We obtained an optimized healthy bone classification
to compare with pathological bone: cortical, trabecular, and flat bone. The osteoblastic metastases (OM) were classified in
nonflat and flat bone. These radiological images were analyzed by using a computerized method. The parameters (gray scale)
calculated were: mean, standard deviation, and coefficient of variation (MGL, SDGL, and CVGL, respectively) based on gray
level histogram analysis. Diagnostic utility was quantified by measurement of parameters on healthy and pathological bone,
yielding quantification of area under the receiver operating characteristic (ROC) curve, AUC.
Results All three image parameters showed high and significant values of AUC when comparing healthy trabecular bone and nonflat bone
OM, showing MGL the best discriminatory ability (0.97). As for flat bones, MGL showed no ability to distinguish between healthy
and flat bone OM (0.50). This could be achieved by using SDGL or CVGL, with both showing a similar diagnostic ability (0.85
and 0.83, respectively).
Conclusion Our results show that the use of gray level parameters quantify healthy bone and osteoblastic metastases zones on digitized
radiographs. This may be helpful as a complementary method for differential diagnosis. Moreover, our method will allow us
to study the evolution of osteoblastic metastases under medical treatment. 相似文献
997.
大学生宽恕与心理健康的相关分析 总被引:3,自引:0,他引:3
李湘晖 《中国健康心理学杂志》2008,16(7):734-737
目的探讨大学生宽恕与心理健康水平的关系。方法采用整群分层抽样法抽取南京市某2所大学本科生323名。采用中国-Mullet宽恕问卷测查大学生的宽恕水平,用症状自评量表(SCL-90)测查被试的心理健康状况。结果大学生总体平均宽恕指数为188.36±40.796。大学生宽恕与SCL总分以及10个因子呈显著的负相关。对大学生的宽恕与心理症状因子进行逐步回归分析.结果偏执、敌对2个因子进入了回归方程。结论目前大多数大学生具有较高的宽恕水平,但仍然有相当一部分大学生的宽恕水平有待提高,且男女生宽恕存在显著差异;大学生宽恕与心理症状呈负相关,宽恕水平越高的学生心理健康状况越良好,宽恕水平越低的人心理健康状况越差。偏执、敌对等对大学生宽恕水平有显著的负面影响。不同学科、性别、年级的大学生宽恕与心理健康的相关程度不同。 相似文献
998.
目的 为了研究中国庚型肝炎病毒(HGV)非结构(NS3)区基因结构特征。方法 利用逆转录-半巢式-聚合酶链反应从河南1份HGV RNA阳性血清获得覆盖HBV NS3全长cDNA的4个片段,并克隆到pcDNAⅡ载体中,采用Sanger双脱氧末端终止法测定全部cDNA序列。结果 发现克隆到的包括HBV NS3区在内的cDNA序列和度为2137个核苷酸,编码711个氨基酸。与国内外已测定的5株全序列的相 相似文献
999.
The identification of the new allele HLA-A*6813, which was found in a woman of Syrian origin and her son, is described. In the sequence analysis the new allele differs from A*68011 by positions 259 (A>G) and 261 (C>G) in exon 2. As the structure is thus identical to the HLA-A consensus sequence it is likely that the new allele originated by gene conversion. At the protein level, the new allele has one amino acid difference from A*6801 (Asn63Glu), which results in a distinct banding pattern in one dimensional-isoelectric focusing. Amino acid residue 63 contributes to the formation of pocket A and B and is thus important for peptide binding. A*6813 was serologically detectable only by two of six polyclonal, but by three monoclonal antisera. The restricted serological A68 activity may be explained by altered peptide binding as presented peptides can affect the serological recognition of major histocompatibility complex (MHC) class I molecules. Moreover, our findings suggest that a possible mismatch with the other known A*68 variants may impair clinical outcome of bone marrow transplantation. 相似文献
1000.
Tobiasch E Kehm R Bahr U Tidona CA Jakob NJ Handermann M Darai G Giese M 《Virus genes》2001,22(2):187-199
Equine arteritis virus (EAV) is a member of the Arteriviridae family, that includes lactate dehydrogenase-elevating virus (LDV), porcine reproductive and respiratory syndrome virus (PRRSV), and simian haemorrhagic fever virus (SHFV). Equine arteritis is a contagious disease of horses and is spread via respiratory or reproductive tract. The objective of the present study is to evaluate the possibility for developing a model system for prevention horses against an EAV infection by DNA vaccination. A cDNA bank from the RNA of EAV was established. This gene library contains the translation unit of the EAV open reading frames (ORF) 1 to 7. The identity of the cDNA was confirmed by nucleotide sequence analysis. Using this defined EAV cDNA gene library the cDNA sequence of the viral ORFs were molecularly cloned into the corresponding sites of well characterized and powerful expression vectors (pCR3.1, pDisplay, and/or pcDNA3.1/HisC).The capability of these recombinant plasmids expressing the gene products of the individual viral ORFs 3 to 5, and 7 in induction of an immune response in mouse system was investigated. The Balb/c mice (ten mice per assay) were inoculated with the DNA of the constructed expression vectors harboring and expressing the EAV cDNA of the viral ORFs. The Balb/c mice were injected with about 100 g DNA diluted in 100 l PBS. The DNA was injected subcutaneously and into the tibialis cranialis muscle (Musculus gastrocnemius). The mice were boosted 3 to 5 times with the same quantities of DNA and under the same conditions at about two week intervals. Control mice received the same amount of parental expression vectors via an identical route and frequency.The pre- and post-vaccinated sera of the individual animals were screened by neutralization tests (NT). Neutralizing antibodies against EAV were detected when the animals were inoculated with the DNA of the expression vectors harboring cDNA of the EAV ORFs 5 and 7. Highest NT-titers were observed when the animals were administered with the cDNA of ORF 5 and/or with the cDNA of the neutralization determinants of EAV that is located on the N-terminal ectodomain of the gene product of ORF 5 between the amino acid positions 1–121. These results obtained from these studies justified proofing the capability of the EAV cDNA sequences of the viral genes including ORFs 5 and 7 in the autologous animal system horse. 相似文献