Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari type I malformation.
Abstract
BACKGROUND: Expression quantitative trait loci (eQTL) play an important role in the
regulation of gene expression. Gene expression levels and eQTLs are expected to vary
from tissue to tissue, and therefore multi-tissue analyses are necessary to fully
understand complex genetic conditions in humans. Dura mater tissue likely interacts
with cranial bone growth and thus may play a role in the etiology of Chiari Type I
Malformation (CMI) and related conditions, but it is often inaccessible and its gene
expression has not been well studied. A genetic basis to CMI has been established;
however, the specific genetic risk factors are not well characterized. RESULTS: We
present an assessment of eQTLs for whole blood and dura mater tissue from individuals
with CMI. A joint-tissue analysis identified 239 eQTLs in either dura or blood, with
79% of these eQTLs shared by both tissues. Several identified eQTLs were novel and
these implicate genes involved in bone development (IPO8, XYLT1, and PRKAR1A), and
ribosomal pathways related to marrow and bone dysfunction, as potential candidates
in the development of CMI. CONCLUSIONS: Despite strong overall heterogeneity in expression
levels between blood and dura, the majority of cis-eQTLs are shared by both tissues.
The power to detect shared eQTLs was improved by using an integrative statistical
approach. The identified tissue-specific and shared eQTLs provide new insight into
the genetic basis for CMI and related conditions.
Type
Journal articleSubject
AdolescentArnold-Chiari Malformation
Bone Development
Child
Child, Preschool
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
Dura Mater
Female
Gene Regulatory Networks
Genotype
Humans
Male
Pentosyltransferases
Polymorphism, Single Nucleotide
Quantitative Trait Loci
beta Karyopherins
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https://hdl.handle.net/10161/15599Published Version (Please cite this version)
10.1186/s12864-014-1211-8Publication Info
Lock, Eric F; Soldano, Karen L; Garrett, Melanie E; Cope, Heidi; Markunas, Christina
A; Fuchs, Herbert; ... Ashley-Koch, Allison E (2015). Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari
type I malformation. BMC Genomics, 16. pp. 11. 10.1186/s12864-014-1211-8. Retrieved from https://hdl.handle.net/10161/15599.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Allison Elizabeth Ashley-Koch
Professor in Medicine
One of my major research foci is in the genetic basis of psychiatric and neurological
disorders. I am currently involved in studies to dissect the genetic etiology of
attention deficit hyperactivity disorder (ADHD), autism, chiari type I malformations,
essential tremor, and neural tube defects. Additional research foci include genetic
modifiers of sickle cell disease, and genetic contributions to birth outcomes, particularly
among African American women.
David B. Dunson
Arts and Sciences Distinguished Professor of Statistical Science
My research focuses on developing new tools for probabilistic learning from complex
data - methods development is directly motivated by challenging applications in ecology/biodiversity,
neuroscience, environmental health, criminal justice/fairness, and more. We seek
to develop new modeling frameworks, algorithms and corresponding code that can be
used routinely by scientists and decision makers. We are also interested in new inference
framework and in studying theoretical properties
Herbert Edgar Fuchs
Professor of Neurosurgery
Clinical neuro-oncology research including collaborations studying molecular genetics
of childhood brain tumors. Potential role of the free electron laser in surgery
of pediatric brain tumors. Current work includes animal models with human brain tumor
xenografts in preclinical studies. Collaboration with the neurooncology laboratory
of Dr. Darell Bigner in preclinical studies of new therapeutic agents.
Gerald Arthur Grant
Allan H. Friedman Distinguished Professor of Neurosurgery
Simon Gray Gregory
Professor in Neurosurgery
Dr. Gregory is a tenured Professor and Director of the Brain Tumor Omics Program (BTOP)
in the Duke Department of Neurosurgery, the Vice Chair of Research in the Department
of Neurology, and Director of the Molecular Genomics Core at the Duke Molecular Physiology
Institute.
As a neurogenomicist, Dr. Gregory applies the experience gained from leading the sequencing
of chromosome 1 for the Human Genome Project to elucidating the mechanisms underlying
multi-factorial
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