Document Detail

Allele drop-out in the MECP2 gene due to G-quadruplex and i-motif sequences when using polymerase chain reaction-based diagnosis for Rett syndrome.
MedLine Citation:
PMID:  20384458     Owner:  NLM     Status:  MEDLINE    
Although few examples are formally documented, all polymerase chain reaction-based testing is theoretically vulnerable to allele drop-out (ADO), the failure to amplify one of the two alleles present in a cell. In a clinical setting, this can lead to false positive or negative diagnosis. We investigated the mechanisms leading to ADO in the MECP2 gene in two unrelated female patients undergoing testing for Rett syndrome. Both the patients had two benign DNA variations, c.819G > T and c.1161C > T, that appeared homozygous due to ADO. Bioinformatics analyses indicate that this region of the MECP2 gene is rich in complex tertiary structures called G-quadruplex and i-motifs, the disruption of which by the c.819G > T and c.1161C > T variants leads to preferential amplification of the variant allele. Other examples of ADO likely occur, and consideration of disrupting G-quadruplex and i-motif structures should be given when this phenomenon is unexpected. We identify factors in both the polymerase chain reaction amplification and the sequencing steps that help overcome ADO.
Carol J Saunders; Michael J Friez; Melanie Patterson; Masha Nzabi; Weiwei Zhao; Chengpeng Bi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Genetic testing and molecular biomarkers     Volume:  14     ISSN:  1945-0257     ISO Abbreviation:  Genet Test Mol Biomarkers     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-13     Completed Date:  2010-07-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101494210     Medline TA:  Genet Test Mol Biomarkers     Country:  United States    
Other Details:
Languages:  eng     Pagination:  241-7     Citation Subset:  IM    
Department of Pathology and Laboratory Medicine, The Children's Mercy Hospitals and Clinics, Kansas City, Missouri 64108, USA.
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MeSH Terms
Base Sequence
DNA / chemistry,  genetics
DNA Primers / genetics
Genetic Testing
Methyl-CpG-Binding Protein 2 / genetics*
Molecular Sequence Data
Nucleic Acid Conformation
Polymerase Chain Reaction / methods
Polymorphism, Single Nucleotide
Rett Syndrome / diagnosis*,  genetics*
Reg. No./Substance:
0/DNA Primers; 0/MECP2 protein, human; 0/Methyl-CpG-Binding Protein 2; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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