Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

A cytosine-thymine (CT)-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer's disease and affects SNCA expression.

Publication ,  Journal Article
Lutz, MW; Saul, R; Linnertz, C; Glenn, O-C; Roses, AD; Chiba-Falek, O
Published in: Alzheimers Dement
October 2015

INTRODUCTION: We recently showed that tagging single-nucleotide polymorphisms across the SNCA locus were significantly associated with increased risk for Lewy body (LB) pathology in Alzheimer's disease (AD) cases. However, the actual genetic variant(s) that underlie the observed associations remain elusive. METHODS: We used a bioinformatics algorithm to catalog structural variants in a region of SNCA intron 4, followed by phased sequencing. We performed a genetic association analysis in autopsy series of LB variant of Alzheimer's disease (LBV/AD) cases compared with AD-only controls. We investigated the biological functions by expression analysis using temporal-cortex samples. RESULTS: We identified four distinct haplotypes within a highly polymorphic low-complexity cytosine-thymine (CT)-rich region. We showed that a specific haplotype conferred risk to develop LBV/AD. We demonstrated that the CT-rich site acts as an enhancer element, where the risk haplotype was significantly associated with elevated levels of SNCA messenger RNA. DISCUSSION: We have discovered a novel haplotype in a CT-rich region in SNCA that contributes to LB pathology in AD patients, possibly via cis-regulation of the gene expression.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Alzheimers Dement

DOI

EISSN

1552-5279

Publication Date

October 2015

Volume

11

Issue

10

Start / End Page

1133 / 1143

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Thymine
  • Risk
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Lewy Body Disease
  • Introns
  • Humans
  • Haplotypes
  • Geriatrics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lutz, M. W., Saul, R., Linnertz, C., Glenn, O.-C., Roses, A. D., & Chiba-Falek, O. (2015). A cytosine-thymine (CT)-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer's disease and affects SNCA expression. Alzheimers Dement, 11(10), 1133–1143. https://doi.org/10.1016/j.jalz.2015.05.011
Lutz, Michael W., Robert Saul, Colton Linnertz, Omolara-Chinue Glenn, Allen D. Roses, and Ornit Chiba-Falek. “A cytosine-thymine (CT)-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer's disease and affects SNCA expression.Alzheimers Dement 11, no. 10 (October 2015): 1133–43. https://doi.org/10.1016/j.jalz.2015.05.011.
Lutz MW, Saul R, Linnertz C, Glenn O-C, Roses AD, Chiba-Falek O. A cytosine-thymine (CT)-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer's disease and affects SNCA expression. Alzheimers Dement. 2015 Oct;11(10):1133–43.
Lutz, Michael W., et al. “A cytosine-thymine (CT)-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer's disease and affects SNCA expression.Alzheimers Dement, vol. 11, no. 10, Oct. 2015, pp. 1133–43. Pubmed, doi:10.1016/j.jalz.2015.05.011.
Lutz MW, Saul R, Linnertz C, Glenn O-C, Roses AD, Chiba-Falek O. A cytosine-thymine (CT)-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer's disease and affects SNCA expression. Alzheimers Dement. 2015 Oct;11(10):1133–1143.
Journal cover image

Published In

Alzheimers Dement

DOI

EISSN

1552-5279

Publication Date

October 2015

Volume

11

Issue

10

Start / End Page

1133 / 1143

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Thymine
  • Risk
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Lewy Body Disease
  • Introns
  • Humans
  • Haplotypes
  • Geriatrics