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A posterior probability of linkage & association study of 111 autism candidate genes
Descriptive
TypeOfResource
Text
TitleInfo
Title
A posterior probability of linkage & association study of 111 autism candidate genes
Identifier
ETD_1679
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051184
Identifier
(type = doi)
doi:10.7282/T3BP030B
Language
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(authority = ISO 639-3:2007);
(type = text)
English
Genre
(authority = marcgt)
theses
Subject
(authority = RUETD)
Topic
Microbiology and Molecular Genetics
Subject
(authority = ETD-LCSH)
Topic
Autism--Genetics aspects
Subject
(authority = ETD-LCSH)
Topic
Autism--Etiology
Abstract
(type = abstract)
Autism is a neurodevelopmental disorder with a complex genetic basis. In this study we investigated the possible involvement of 111 candidate genes in autism by studying 386 patient families from the Autism Genetic Resource Exchange (AGRE). These genes were selected based on their functions that relate to the neurotransmission or central developmental system. In phase 1 of the study, 1497 tagSNPs were selected to efficiently capture the haplotype information of each gene and were genotyped in 265 AGRE nuclear families. The cleaned genotype data were analyzed through the Kelvin program to compute values of Posterior Probability of Linkage (PPL) and Posterior Probability of LD given linkage (PPLD), which directly measure the probability of linkage and/or association. Consistent supportive evidence for linkage was observed for EPHB6-EPHA1 locus at the 7q34 region by two- and multi-point PPL analysis. Some evidence for association was obtained from the intronic SNP rs2242601 of the EPHA1 gene (PPLD = 10.4%), and multiple SNPs from the MECP2 gene at Xq28 (PPLD range from 5~9%). Using a subset of the newly released AGRE genotype data from the Affymetrix 5.0 high-density SNP array, further evidence for association was obtained for 6 markers located 90kb distal of EPHA1 gene (PPLD range from 21% to 40%).
In phase 2 of this study, in an attempt to conduct fine mapping as well as to replicate our phase 1 results in a set of 123 additional AGRE family samples, additional SNPs were selected from the EPHA1 and MECP2 gene region for fine-scale analysis. Strong support of association with autism was observed for the markers downstream of the EPHA1 gene using the original families, with the SNP rs7801889 showing a high PPLD value of 62%. Markers from the MECP2 gene region remained moderately associated with PPLD values around 8%. Nonetheless, none of the SNPs showed any support for association in the additional family samples. These mixed preliminary results suggested the polymorphisms within and downstream of the Ephrin receptor A1 gene as potential novel susceptibility loci for autism. Limited support for the role of MECP2 in autism etiology was also observed.
In phase 2 of this study, in an attempt to conduct fine mapping as well as to replicate our phase 1 results in a set of 123 additional AGRE family samples, additional SNPs were selected from the EPHA1 and MECP2 gene region for fine-scale analysis. Strong support of association with autism was observed for the markers downstream of the EPHA1 gene using the original families, with the SNP rs7801889 showing a high PPLD value of 62%. Markers from the MECP2 gene region remained moderately associated with PPLD values around 8%. Nonetheless, none of the SNPs showed any support for association in the additional family samples. These mixed preliminary results suggested the polymorphisms within and downstream of the Ephrin receptor A1 gene as potential novel susceptibility loci for autism. Limited support for the role of MECP2 in autism etiology was also observed.
PhysicalDescription
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electronic resource
Extent
xik 122 p. : ill.
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application/pdf
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Note
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Ph.D.
Note
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Includes bibliographical references (p. 74-83)
Note
(type = statement of responsibility)
by Fang Chen
Name
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Chen
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Fang
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1975
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author
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Fang Chen
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Yu
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(type = given)
Lei
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chair
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Advisory Committee
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Lei Yu
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Matise
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Tara
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internal member
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Advisory Committee
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Tara Cox Matise
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Tischfield
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Jay
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internal member
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Advisory Committee
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Jay Tischfield
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Millonig
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Jim
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Advisory Committee
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Jim Millonig
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Brzustowicz,
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Linda
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internal member
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Advisory Committee
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Linda Brzustowicz,
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Gorden
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Derek
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outside member
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Advisory Committee
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Derek Gorden
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
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2009
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2009-05
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xx
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NjNbRU
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Rutgers University Electronic Theses and Dissertations
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ETD
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Genre
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ETD doctoral
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Rights
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The author owns the copyright to this work.
Copyright
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Copyright protected
Availability
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Open
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Non-exclusive ETD license
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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ETD
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application/pdf
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application/x-tar
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3235840
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