Increasing DNA marker informativeness in hereditary canine motor neuron disease
Increasing DNA marker informativeness in hereditary canine motor neuron disease
批准号:
7559659
负责人:
Martin J Pinter
金额:
$7.65万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-02-01 至 2011-01-31
关键词:
AxonCanis familiarisCell DeathCellular biologyDNADNA MarkersDiseaseEnvironmentFailureFamilial Motor Neuron DiseaseGenesGeneticGenomicsHeterozygoteHumanInbreedingInheritedInstitutesInvestigationLightMapsMicrosatellite RepeatsModelingMotorMotor Neuron DiseaseMotor NeuronsMutationNeurodegenerative DisordersNeuronsPathogenesisPathologyPhenotypePropertyPublicationsResolutionResourcesSOD1 geneSingle Nucleotide Polymorphism MapSolutionsSpinal Muscular AtrophyStudy modelsSynapsesSynaptic Transmissiondisease phenotypefunctional lossgenetic linkage analysisgenetic pedigreegenome wide association studyinsightneuron lossnovel
中文摘要
遗传性犬脊髓性肌萎缩症(HCSMA)是一种遗传性运动模型,
神经元疾病(MND),与人类MND和其他神经元疾病具有相同的特征。
神经退行性疾病弱点首先出现在HCSMA中,因为
运动神经末梢的突触传递。这种紊乱最终表现为运动性
单位故障,并进展为运动终末变性,运动轴突丢失,以及,在
HCSMA杂合子中运动神经元丢失最少。我们最近获得的证据
表明运动神经元活动是进展的主要因素,
这种退化始于运动神经末梢虽然我们知道
关于HCSMA的病理学和细胞生物学,缺陷基因的身份,
仍然未知。先前的研究表明,HCSMA不是由
导致家族性MND的两个最突出的基因(SOD1和SMN)突变,
人类这表明,HCSMA中缺陷基因的鉴定将提供新的
导致MND表型的机制。最近尝试执行
使用低分辨率微卫星标记集的连锁分析未能建立
在HCSMA菌落内存在显著联系。主要问题是,
微卫星标记的多态性不足以产生显著的连锁
信息.可能的原因是大量的近亲繁殖,
在HCSMA殖民地发生的解决这个问题的一个办法是
大大增加了标记的数量。最近发表的犬SNP
map及其作为64k微阵列的商业可用性现在使得这种方法
可行我们现在建议对HCSMA的现有DNA进行连锁研究
谱系使用这些新的资源作为第一步,以确定有缺陷的
HCSMA基因
英文摘要
Hereditary Canine Spinal Muscular Atrophy (HCSMA) is an inherited model of motor
neuron disease (MND) that shares features with human MND and other
neurodegenerative diseases. Weakness first appears in HCSMA because of decreased
synaptic transmission at motor terminals. The disorder eventually manifests as motor
unit failure and progresses to motor terminal degeneration, motor axon loss, and, at
least in HCSMA heterozygotes, motor neuron loss. Evidence we have obtained recently
demonstrates that motor neuron activity is a major contributing factor to the progression
of HCSMA and that degeneration begins at the motor terminal. Although much is known
about the pathology and cell biology of HCSMA, the identity of the defective gene
remains unknown. Previous studies have shown that HCSMA is not caused by
mutations in 2 of the most prominent genes (SOD1 and SMN) that cause familial MND in
humans. This shows that identification of the defective gene in HCSMA will shed new
light on mechanisms that cause the MND phenotype. Recent attempts to perform
linkage analysis using a low resolution microsatellite marker set failed to establish
significant linkage within the HCSMA colony. The main problem is that many of the
microsatellite markers are not sufficiently polymorphic to yield significant linkage
information. The likely cause of this is the extensive amount of inbreeding that has
occurred in the HCSMA colony over the years. One solution to this problem would be to
dramatically increase the number of markers. The recent publication of a canine SNP
map and its commercial availability as a 64k microarray now make this approach
feasible. We now propose to perform a linkage study on existing DNA from the HCSMA
pedigree using these new resources as a first step towards identification of the defective
gene in HCSMA.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Wild-type nerve grafting promotes reinnervation of SOD1 muscle
-
批准号:8512110
-
项目类别:
-
资助金额:$23.4万
-
财政年份:2013
-
负责人:Martin J Pinter
-
依托单位:
Mechanisms of retrograde signaling between muscle and motor neurons
-
批准号:8016691
-
项目类别:
-
资助金额:$18.99万
-
财政年份:2010
-
负责人:Martin J Pinter
-
依托单位:
Mechanisms of retrograde signaling between muscle and motor neurons
-
批准号:7897453
-
项目类别:
-
资助金额:$23.25万
-
财政年份:2010
-
负责人:Martin J Pinter
-
依托单位:
Mechanisms that maintain motoneuron properties
-
批准号:6645012
-
项目类别:
-
资助金额:$5.57万
-
财政年份:2002
-
负责人:Martin J Pinter
-
依托单位:
Mechanisms that maintain motoneuron properties
-
批准号:6481271
-
项目类别:
-
资助金额:$5.57万
-
财政年份:2001
-
负责人:Martin J Pinter
-
依托单位:
Mechanisms that maintain motoneuron properties
-
批准号:6333251
-
项目类别:
-
资助金额:$5.57万
-
财政年份:2000
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:2891870
-
项目类别:
-
资助金额:$29.84万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:3418563
-
项目类别:
-
资助金额:$20.88万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE-NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:6668670
-
项目类别:
-
资助金额:$28.88万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:2269565
-
项目类别:
-
资助金额:$20.76万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:6496595
-
项目类别:
-
资助金额:$3.24万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE-NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:6574239
-
项目类别:
-
资助金额:$28.56万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:2714518
-
项目类别:
-
资助金额:$14.83万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:6596162
-
项目类别:
-
资助金额:$2.89万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE-NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:6801478
-
项目类别:
-
资助金额:$28.88万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:2269564
-
项目类别:
-
资助金额:$19.96万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:6188015
-
项目类别:
-
资助金额:$30.61万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE-NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:6943437
-
项目类别:
-
资助金额:$28.88万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE-NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:7116895
-
项目类别:
-
资助金额:$28.2万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
MOTOR NEURON DISEASE--NEUROPHYSIOLOGY AND PATHOLOGY
-
批准号:6027394
-
项目类别:
-
资助金额:$14.45万
-
财政年份:1993
-
负责人:Martin J Pinter
-
依托单位:
海外基金