Evidence map›Paper›PMID 21771879›Full record

ArticlePhysiological genomics2011

Identifying functional single nucleotide polymorphisms in the human CArGome.

Craig C Benson, Qian Zhou, Xiaochun Long, Joseph M Miano

Open access · greenAbstract read
In one paragraph

Article in Physiological genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Serum Response Factor Is Essential for Maintenance of Podocyte Structure and Function.Journal of the American Society of Nephrology : JASN · 2018
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. A CRISPR Path to Engineering New Genetic Mouse Models for Cardiovascular Research.Arteriosclerosis, thrombosis, and vascular biology · 2016
    Review
  17. Multi-phenotypic Role of Serum Response Factor in the Gastrointestinal System.Journal of neurogastroenterology and motility · 2016
    Review
  18. Article
  19. Transcriptional control of cardiac fibroblast plasticity.Journal of molecular and cellular cardiology · 2016
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Craig C BensonUniversity of Rochester Medical Center, Rochester, NY, USA.
Qian Zhou
Xiaochun Long
Joseph M Miano
University of Rochester · USUniversity of Rochester Medical Center · US

Funding

MOLECULAR CONTROL--SMOOTH MUSCLE CALPONIN EXPRESSIONR01HL062572 · NHLBI · UNIVERSITY OF ROCHESTER · PI MIANO, JOSEPH M · 1999 to 2011
$2.9M
Bifunctionality of Myocardin in MyogenesisR01HL091168 · NHLBI · UNIVERSITY OF ROCHESTER · PI MIANO, JOSEPH M · 2008 to 2011
$1.5M
NHLBI NIH HHS HL-091168NHLBI NIH HHS HL-62572
6 · The paper itself

Abstract

Regulatory SNPs (rSNPs) reside primarily within the nonprotein coding genome and are thought to disturb normal patterns of gene expression by altering DNA binding of transcription factors. Nevertheless, despite the explosive rise in SNP association studies, there is little information as to the function of rSNPs in human disease. Serum response factor (SRF) is a widely expressed DNA-binding transcription factor that has variable affinity to at least 1,216 permutations of a 10 bp transcription factor binding site (TFBS) known as the CArG box. We developed a robust in silico bioinformatics screening method to evaluate sequences around RefSeq genes for conserved CArG boxes. Utilizing a predetermined phastCons threshold score, we identified 8,252 strand-specific CArGs within an 8 kb window around the transcription start site of 5,213 genes, including all previously defined SRF target genes. We then interrogated this CArG dataset for the presence of previously annotated common polymorphisms. We found a total of 118 unique CArG boxes harboring a SNP within the 10 bp CArG sequence and 1,130 CArG boxes with SNPs located just outside the CArG element. Gel shift and luciferase reporter assays validated SRF binding and functional activity of several new CArG boxes. Importantly, SNPs within or just outside the CArG box often resulted in altered SRF binding and activity. Collectively, these findings demonstrate a powerful approach to computationally define rSNPs in the human CArGome and provide a foundation for similar analyses of other TFBS. Such information may find utility in genetic association studies of human disease where little insight is known regarding the functionality of rSNPs.

Indexed as

Base SequenceComputational BiologyConserved SequenceGenome, HumanHistonesHumansInternetMolecular Sequence AnnotationMolecular Sequence DataMultigene FamilyPolymorphism, Single NucleotidePromoter Regions, GeneticRegulatory Sequences, Nucleic AcidReproducibility of ResultsSerum Response FactorTranscription Initiation SiteHistonesSerum Response Factor

Identifiers

PMID21771879
PMCPMC3180741
OpenAlexW1972285104

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.