NDLI: Cis-Regulatory Variants Affect CHRNA5 mRNA Expression in Populations of African and European Ancestry

Content Provider	PubMed Central
Author	Wang, Jen-chyong Spiegel, Noah Bertelsen, Sarah Le, Nhung Mckenna, Nicholas Budde, John P. Harari, Oscar Kapoor, Manav Brooks, Andrew Hancock, Dana Tischfield, Jay Tatiana, Foroud Bierut, Laura J. Steinbach, Joe Henry Edenberg, Howard J. Traynor, Bryan J. Goate, Alison M.
Editor	Miao, Xiaoping
Copyright Year	2013
Abstract	Variants within the gene cluster encoding α3, α5, and β4 nicotinic receptor subunits are major risk factors for substance dependence. The strongest impact on risk is associated with variation in the CHRNA5 gene, where at least two mechanisms are at work: amino acid variation and altered mRNA expression levels. The risk allele of the non-synonymous variant (rs16969968; D398N) primarily occurs on the haplotype containing the low mRNA expression allele. In populations of European ancestry, there are approximately 50 highly correlated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and the adjacent PSMA4 gene region that are associated with CHRNA5 mRNA levels. It is not clear which of these variants contribute to the changes in CHRNA5 transcript level. Because populations of African ancestry have reduced linkage disequilibrium among variants spanning this gene cluster, eQTL mapping in subjects of African ancestry could potentially aid in defining the functional variants that affect CHRNA5 mRNA levels. We performed quantitative allele specific gene expression using frontal cortices derived from 49 subjects of African ancestry and 111 subjects of European ancestry. This method measures allele-specific transcript levels in the same individual, which eliminates other biological variation that occurs when comparing expression levels between different samples. This analysis confirmed that substance dependence associated variants have a direct cis-regulatory effect on CHRNA5 transcript levels in human frontal cortices of African and European ancestry and identified 10 highly correlated variants, located in a 9 kb region, that are potential functional variants modifying CHRNA5 mRNA expression levels.
Related Links	http://dx.doi.org/10.1371/journal.pone.0080204
Starting Page	80204
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Validating Discovered Cis-Acting Regulatory Genetic Variants: Application of an Allele Specific Expression Approach to HapMap Populations

Genotypic and Allelic Variability in CYP19A1 among Populations of African and European Ancestry

Genotype-Based Test in Mapping Cis-Regulatory Variants from Allele-Specific Expression Data

Dissecting the Within-Africa Ancestry of Populations of African Descent in the Americas

The Effect of ACACB cis-Variants on Gene Expression and Metabolic Traits

Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children

Genome-Wide Local Ancestry Approach Identifies Genes and Variants Associated with Chemotherapeutic Susceptibility in African Americans

Polymorphisms of Estrogen Metabolism-Related Genes and Prostate Cancer Risk in Two Populations of African Ancestry

Variation of Gene Expression Associated with Colonisation of an Anthropized Environment: Comparison between African and European Populations of Drosophila simulans

Cis-Regulatory Variants Affect CHRNA5 mRNA Expression in Populations of African and European Ancestry

Similar Documents

Validating Discovered Cis-Acting Regulatory Genetic Variants: Application of an Allele Specific Expression Approach to HapMap Populations

Genotypic and Allelic Variability in CYP19A1 among Populations of African and European Ancestry

Genotype-Based Test in Mapping Cis-Regulatory Variants from Allele-Specific Expression Data

Dissecting the Within-Africa Ancestry of Populations of African Descent in the Americas

The Effect of ACACB cis-Variants on Gene Expression and Metabolic Traits

Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children

Genome-Wide Local Ancestry Approach Identifies Genes and Variants Associated with Chemotherapeutic Susceptibility in African Americans

Polymorphisms of Estrogen Metabolism-Related Genes and Prostate Cancer Risk in Two Populations of African Ancestry

Variation of Gene Expression Associated with Colonisation of an Anthropized Environment: Comparison between African and European Populations of Drosophila simulans

Cis-Regulatory Variants Affect CHRNA5 mRNA Expression in Populations of African and European Ancestry