Allelic mRNA expression imbalance in C-type lectins reveals a frequent regulatory SNP in the human surfactant protein A (SP-A) gene

A. K. Azad, A. Curtis, A. Papp, A. Webb, Daren L Knoell, W. Sadee, L. S. Schlesinger

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Genetic variation in C-type lectins influences infectious disease susceptibility but remains poorly understood. We used allelic mRNA expression imbalance (AEI) technology for surfactant protein (SP)-A1, SP-A2, SP-D, dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), macrophage mannose receptor (MRC1) and Dectin-1, expressed in human macrophages and/or lung tissues. Frequent AEI, an indicator of regulatory polymorphisms, was observed in SP-A2, SP-D and DC-SIGN. AEI was measured for SP-A2 in 38 lung tissues using four marker single-nucleotide polymorphisms (SNPs) and was confirmed by next-generation sequencing of one lung RNA sample. Genomic DNA at the SP-A2 DNA locus was sequenced by Ion Torrent technology in 16 samples. Correlation analysis of genotypes with AEI identified a haplotype block, and, specifically, the intronic SNP rs1650232 (30% minor allele frequency); the only variant consistently associated with an approximately twofold change in mRNA allelic expression. Previously shown to alter a NAGNAG splice acceptor site with likely effects on SP-A2 expression, rs1650232 generates an alternative splice variant with three additional bases at the start of exon 3. Validated as a regulatory variant, rs1650232 is in partial linkage disequilibrium with known SP-A2 marker SNPs previously associated with risk for respiratory diseases including tuberculosis. Applying functional DNA variants in clinical association studies, rather than marker SNPs, will advance our understanding of genetic susceptibility to infectious diseases.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalGenes and Immunity
Volume14
Issue number2
DOIs
StatePublished - Mar 1 2013

Fingerprint

Pulmonary Surfactant-Associated Protein A
C-Type Lectins
Surface-Active Agents
Single Nucleotide Polymorphism
varespladib methyl
Messenger RNA
Genes
Pulmonary Surfactant-Associated Protein D
Proteins
Lung
Dendritic Cells
Communicable Diseases
DNA
Macrophages
Technology
RNA Splice Sites
Somatostatin-Secreting Cells
Disease Susceptibility
Linkage Disequilibrium
Genetic Predisposition to Disease

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Allelic mRNA expression imbalance in C-type lectins reveals a frequent regulatory SNP in the human surfactant protein A (SP-A) gene. / Azad, A. K.; Curtis, A.; Papp, A.; Webb, A.; Knoell, Daren L; Sadee, W.; Schlesinger, L. S.

In: Genes and Immunity, Vol. 14, No. 2, 01.03.2013, p. 99-106.

Research output: Contribution to journalArticle

Azad, A. K. ; Curtis, A. ; Papp, A. ; Webb, A. ; Knoell, Daren L ; Sadee, W. ; Schlesinger, L. S. / Allelic mRNA expression imbalance in C-type lectins reveals a frequent regulatory SNP in the human surfactant protein A (SP-A) gene. In: Genes and Immunity. 2013 ; Vol. 14, No. 2. pp. 99-106.
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