SELECTIVE MECHANISMS MAINTAINING H-2 POLYMORPHISMS
SELECTIVE MECHANISMS MAINTAINING H-2 POLYMORPHISMS
批准号:
2179931
负责人:
Wayne K. Potts
金额:
$19.59万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-01-01 至 1998-06-30
中文摘要
主要组织相容性的1类和11类基因产物
复合体(MHC)将外来抗原递送给T淋巴细胞,并
因此,这是免疫反应的重要组成部分。这些基因是
也是脊椎动物已知的最多态的基因座。它有
一般认为,这种维护是史无前例的
遗传多样性是由于
不同种类的病原体和寄生虫,它们各自都是地方病
物种。然而,其中一个最关键的失败
预测,对特定传染病的易感性
应该与某些MHC等位基因相关,造成了混乱。
各种各样的数据表明,这些多态是
通过某种形式的强平衡维持在自然种群中
选择。尽管已经假设了许多选择性机制
为了维护这些多态,几乎没有
在确定哪些机制方面取得了进展
实际上对自然种群中的MHC基因起作用。我们建议
直接衡量维持MHC的选择性机制
通过分析圈养野鼠的健康成分来实现多样性
人口。这种总体级别的方法允许测试
永远无法在实验室中检验的假设(例如
与频率相关的假设),并将直接回答
MHC基因多态如何影响适合度的基本问题
关于个人的。我们将检查以下健身要素。
MHC基因分型对不同病死率的影响
繁殖成功将被衡量。这些数据将允许
检验许多基于疾病的假设,如杂合子
优势和频率相关的选择。交配偏好
将通过观察和观察确定附件内的
亲子关系排除技术(例如,遗传指纹)。
交配偏好也将在实验室进行测试,这是
将允许控制自然环境中固有的混杂变量
社会制度。有利于MHC杂合子的传输失真
将通过检查信息丰富的实验室匹配来进行测试
出生时与孟德尔人预期的偏差。人口
遗传学模型表明,MHC多态的维持
需要相对极端的选择级别,运行
在生存或生殖特征上。我们对这个问题的无知
这种选择的方式是我们对如何选择的一个重大差距
病原体和脊椎动物的免疫系统相互作用。
英文摘要
Class 1 and 11 gene products of the major histocompatibility
complex (MHC) present foreign antigens to T-lymphocytes and are
thus essential components of the immune response. These genes are
also the most polymorphic loci known for vertebrates. It has
generally been assumed that the maintenance of this unprecedented
genetic diversity is due to the selective forces created by the
diverse group of pathogens and parasites that are endemic to each
species. However, the failure of one of the most critical
predictions, that susceptibility to specific infectious diseases
should correlate with certain MHC alleles, has created confusion.
A wide variety of data indicate that these polymorphisms are
maintained in natural populations by some form of strong balancing
selection. Although many selective mechanisms have been postulated
to contribute to the maintenance of these polymorphisms, little
progress has been made towards identifying which mechanisms
actually operate on MHC genes in natural populations. We propose
to measure directly the selective mechanisms that maintain MHC
diversity by analyzing fitness components in a captive wild mouse
population. This population level approach allows the testing of
hypotheses that could never be tested in the laboratory (e.g.
frequency dependent hypotheses) and will directly answer the
fundamental question of how MHC polymorphisms affect the fitness
of individuals. The following fitness components will be examined.
The influence of MHC genotypes on differential mortality and
reproductive success will be measured. These data will allow
testing of numerous disease based hypotheses such as heterozygote
advantage and frequency dependent selection. Mating preferences
within the enclosure will be determined through observations and
paternity exclusion techniques (e.g. genetic fingerprinting).
Mating preferences will also be tested in the laboratory, which
will allow control of confounding variables inherent in natural
social systems. Transmission distortion favoring MHC heterozygotes
will be tested by checking informative laboratory matings for
deviations from Mendelian expectations at birth. Population
genetics models indicate that the maintenance of MHC polymorphisms
requires relatively extreme levels of selection, operating either
on survival or reproductive traits. Our ignorance concerning the
mode of this selection is a major gap in our understanding of how
pathogens and the vertebrate immune system interact.
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SELECTIVE MECHANISMS MAINTAINING H-2 POLYMORPHISMS
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批准号:2444678
-
项目类别:
-
资助金额:$21.69万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H 2 POLYMORPHISMS
-
批准号:6385717
-
项目类别:
-
资助金额:$26.89万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H 2 POLYMORPHISMS
-
批准号:6481728
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项目类别:
-
资助金额:$4.04万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H 2 POLYMORPHISMS
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批准号:6606845
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项目类别:
-
资助金额:$5.0万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H 2 POLYMORPHISMS
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批准号:6519295
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项目类别:
-
资助金额:$27.69万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
Ecological functional genomics: phenotyping Hox mutants
-
批准号:6810531
-
项目类别:
-
资助金额:$25.49万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS THAT MAINTAIN MHC POLYMORPHISMS
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批准号:3042847
-
项目类别:
-
资助金额:$2.8万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H-2 POLYMORPHISMS
-
批准号:2179932
-
项目类别:
-
资助金额:$19.21万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
Ecological functional genomics: phenotyping Hox mutants
-
批准号:7234320
-
项目类别:
-
资助金额:$30.83万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H 2 POLYMORPHISMS
-
批准号:6179565
-
项目类别:
-
资助金额:$26.02万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H-2 POLYMORPHISMS
-
批准号:2179933
-
项目类别:
-
资助金额:$20.86万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H-2 POLYMORPHISMS
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批准号:2807131
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项目类别:
-
资助金额:$6.05万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS MAINTAINING H 2 POLYMORPHISMS
-
批准号:2908991
-
项目类别:
-
资助金额:$25.27万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
Ecological functional genomics: phenotyping Hox mutants
-
批准号:6899847
-
项目类别:
-
资助金额:$25.49万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
Ecological functional genomics: phenotyping Hox mutants
-
批准号:7061654
-
项目类别:
-
资助金额:$31.75万
-
财政年份:1989
-
负责人:Wayne K. Potts
-
依托单位:
SELECTIVE MECHANISMS THAT MAINTAIN MHC POLYMORPHISMS
-
批准号:3042846
-
项目类别:
-
资助金额:$2.0万
-
财政年份:1988
-
负责人:Wayne K. Potts
-
依托单位: