GENETIC AND MOLECULAR ANALYSIS OF IMPRINTED GENES
GENETIC AND MOLECULAR ANALYSIS OF IMPRINTED GENES
批准号:
2190650
负责人:
WILLIAM A HELD
金额:
$21.25万
依托单位国家:
美国
项目类别:
财政年份:
1995
资助国家:
美国
项目状态:
已结题
起止时间:
1995-01-01 至 1996-12-31
关键词:
DNA methylation alleles animal genetic material tag biochemical evolution developmental genetics endonuclease gel electrophoresis gene expression gene mutation genetic library genetic mapping genetically modified animals genomic imprinting genotype in situ hybridization laboratory mouse molecular cloning northern blottings nucleic acid sequence polymerase chain reaction southern blotting
中文摘要
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英文摘要
Genomic imprinting results in the specific expression of parental alleles
for endogenous genes that play significant roles in growth regulation of
mammalian embryos. Disregulation of these genes appears to be associated
with neoplasias and neonatal cancers in humans and a number of
developmental syndromes. Five imprinted genes have been characterized in
the mouse but the total number of imprinted genes and their potential
roles in cancer and other diseases is unknown. A method of screening the
mouse genome for new imprinted genes has been developed that is based upon
differential methylation of CpG islands. This proposal describes
restriction landmark genomic scanning (RLGS) which uses high resolution
two-dimensional gel electrophoresis to identify end-labeled, rare-site
cleavages of genomic DNA using Not I and similar endonucleases. Two
thousand RLGS landmarks can be identified as spots in a single two
dimensional gel and additional landmarks for a genome can be readily
produced with different restriction enzyme combinations. Genetic variation
for these landmarks has been identified between common inbred strains and
between laboratory mice and other Mus species. We have screened more than
2000 strain-specific sites in the mouse genome for differential
methylation of parental genes using a landmark enzyme that is methylation
sensitive (NotI). Parent allele-specific NotI digestion was detected by
analyzing reciprocal F1 combinations between various mouse genotypes.
Eight loci were identified that showed differential methylation of
parental genes. One locus on mouse chromosome 11 has been characterized
which shows a derived amino acid sequence homology with the U2 small
nucleoprotein auxiliary factor small subunit -U2AF binding protein.
Molecular clones for a second locus have been identified and work is in
progress to characterize the imprinted gene. This proposal outlines an
experimental program that will characterize five additional imprinted RLGS
loci (Irlgs loci) that have been identified as a first step in determining
the molecular basis for imprinting and the evolutionary reasons for
sustaining monoallelic expression of different genes. We also propose to
screen an additional 3500 - 4000 landmarks in the mouse genome for new
Irlgs loci as a means of determining the total number of endogenous genes
that are imprinted. The cloned sequences for imprinted mouse genes can be
used to identify the homologous human genes and their linkage in the human
genome. This information will provide a more complete opportunity to
establish the number of imprinted genes in the mammalian genome and their
potential involvement in cancer and other developmental disorders in
humans.
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Sites of Developmental & Tissue-specific DNA Methylation
-
批准号:6891365
-
项目类别:
-
资助金额:$30.43万
-
财政年份:2004
-
负责人:WILLIAM A HELD
-
依托单位:
Sites of Developmental & Tissue-specific DNA Methylation
-
批准号:6778565
-
项目类别:
-
资助金额:$30.08万
-
财政年份:2004
-
负责人:WILLIAM A HELD
-
依托单位:
Sites of Developmental & Tissue-specific DNA Methylation
-
批准号:7065198
-
项目类别:
-
资助金额:$30.06万
-
财政年份:2004
-
负责人:WILLIAM A HELD
-
依托单位:
Sites of Developmental & Tissue-specific DNA Methylation
-
批准号:7225212
-
项目类别:
-
资助金额:$29.54万
-
财政年份:2004
-
负责人:WILLIAM A HELD
-
依托单位:
GENETIC AND PHYSICAL ANALYSIS OF RESTRICTION LANDMARKS
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批准号:2112616
-
项目类别:
-
资助金额:$18.79万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
RESTRICTION LANDMARK GENOMIC ANALYSIS OF CANCER
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批准号:6376185
-
项目类别:
-
资助金额:$27.1万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
Restriction Landmark Genomic Analysis of Cancer
-
批准号:6919140
-
项目类别:
-
资助金额:$35.56万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
Restriction Landmark Genomic Analysis of Cancer
-
批准号:6684039
-
项目类别:
-
资助金额:$34.73万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
Restriction Landmark Genomic Analysis of Cancer
-
批准号:7081297
-
项目类别:
-
资助金额:$35.14万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
GENETIC AND PHYSICAL ANALYSIS OF RESTRICTION LANDMARKS
-
批准号:2112615
-
项目类别:
-
资助金额:$15.02万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
GENETIC AND MOLECULAR ANALYSIS OF IMPRINTED GENES
-
批准号:2190651
-
项目类别:
-
资助金额:$25.38万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
RESTRICTION LANDMARK GENOMIC ANALYSIS OF CANCER
-
批准号:2895398
-
项目类别:
-
资助金额:$25.57万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
RESTRICTION LANDMARK GENOMIC ANALYSIS OF CANCER
-
批准号:2700638
-
项目类别:
-
资助金额:$24.84万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
RESTRICTION LANDMARK GENOMIC ANALYSIS OF CANCER
-
批准号:2397400
-
项目类别:
-
资助金额:$24.39万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
RESTRICTION LANDMARK GENOMIC ANALYSIS OF CANCER
-
批准号:6172802
-
项目类别:
-
资助金额:$26.32万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
Restriction Landmark Genomic Analysis of Cancer
-
批准号:6767571
-
项目类别:
-
资助金额:$35.14万
-
财政年份:1995
-
负责人:WILLIAM A HELD
-
依托单位:
ANDROGEN CONDITIONAL CARCINOGENESIS IN TRANSGENIC MICE
-
批准号:3195318
-
项目类别:
-
资助金额:$15.18万
-
财政年份:1990
-
负责人:WILLIAM A HELD
-
依托单位:
ANDROGEN CONDITIONAL CARCINOGENESIS IN TRANSGENIC MICE
-
批准号:3195320
-
项目类别:
-
资助金额:$14.14万
-
财政年份:1990
-
负责人:WILLIAM A HELD
-
依托单位:
ANDROGEN CONDITIONAL CARCINOGENESIS IN TRANSGENIC MICE
-
批准号:2093919
-
项目类别:
-
资助金额:$15.36万
-
财政年份:1990
-
负责人:WILLIAM A HELD
-
依托单位:
ANDROGEN CONDITIONAL CARCINOGENESIS IN TRANSGENIC MICE
-
批准号:3195322
-
项目类别:
-
资助金额:$16.26万
-
财政年份:1990
-
负责人:WILLIAM A HELD
-
依托单位:
海外基金