Characterization of the poly-T variant in the TOMM40 gene in diverse populations.

PloS One
C LinnertzO Chiba-Falek

Abstract

We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T, rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset of Alzheimer's disease and with cognitive performance in elderly. Three allele groups were defined for rs10524523, hereafter '523', based on the number of 'T'-residues: 'Short' (S, T≤19), 'Long' (L, 20≤T≤29) and 'Very Long' (VL, T≥30). Homopolymers, particularly long homopolymers like '523', are difficult to genotype because 'slippage' occurs during PCR-amplification. We initially genotyped this locus by PCR-amplification followed by Sanger-sequencing. However, we recognized the need to develop a higher-throughput genotyping method that is also accurate and reliable. Here we describe a new '523' genotyping assay that is simple and inexpensive to perform in a standard molecular genetics laboratory. The assay is based on the detection of differences in PCR-fragment length using capillary electrophoresis. We discuss technical problems, solutions, and the steps taken for validation. We employed the novel assay to investigate the '523' allele frequencies in different ethnicities. Whites and Hispanics have similar frequencies of S/L/VL alleles (0.45/0.11/0.44 and 0.43/0.09/0.48, r...Continue Reading

References

Jan 11, 2003·Clinical Chemistry and Laboratory Medicine : CCLM·Werner KochAdnan Kastrati
Mar 29, 2008·Metabolic Syndrome and Related Disorders·Tamara NelsonJeanette J McCarthy
Dec 24, 2009·The Pharmacogenomics Journal·A D RosesE M Reiman
Mar 20, 2010·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Michael W LutzAllen D Roses
Jul 14, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Aleksandra Maruszak, Cezary Żekanowski
Dec 3, 2010·The EPMA Journal·Iris GrossmanAllen D Roses
Jul 26, 2011·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Sterling C JohnsonMark A Sager
Aug 9, 2011·Neurobiology of Aging·Su Hee ChuRobert A Sweet
Aug 10, 2011·Archives of Neurology·Carlos CruchagaUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Oct 20, 2011·Journal of Alzheimer's Disease : JAD·Aleksandra MaruszakCezary Zekanowski

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Citations

Jan 2, 2016·Pharmacological Reports : PR·Justyna GodyńBarbara Malawska
Aug 28, 2015·International Journal of Stroke : Official Journal of the International Stroke Society·Donald M LyallJoanna M Wardlaw
Mar 3, 2015·The Journal of the American Dental Association·Thomas M BraunWilliam V Giannobile
Apr 5, 2016·Current Neurology and Neuroscience Reports·Michael W LutzAllen D Roses
Sep 24, 2013·Mutation Research. Reviews in Mutation Research·Varinderpal S Dhillon, Michael Fenech
Sep 28, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Allen D RosesKathleen A Welsh-Bohmer
Oct 10, 2013·Neuromuscular Disorders : NMD·F L MastagliaUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Jan 21, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Colton LinnertzOrnit Chiba-Falek
Sep 28, 2013·Biochimica Et Biophysica Acta·Russell H SwerdlowShaharyar M Khan
May 22, 2016·Journal of the Neurological Sciences·Alexandra M V WennbergMarilyn S Albert
Jun 14, 2016·Pharmacogenomics·Ramón CacabelosJuan Carlos Carril
Dec 20, 2012·Clinical Pharmacology and Therapeutics·D G CrenshawA D Roses
May 8, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Allen RosesMichael Lutz
Nov 11, 2017·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Akira NishimuraAllen D Roses
Dec 4, 2019·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Inga ProkopenkoLefkos T Middleton
Apr 24, 2020·Current Alzheimer Research·Michal PrendeckiWojciech Kozubski
Oct 6, 2020·Journal of Alzheimer's Disease : JAD·Remy CardosoCatarina Resende Oliveira
Apr 28, 2020·Neurology. Genetics·Parker L BussiesJeffery M Vance
Sep 26, 2017·Expert Review of Precision Medicine and Drug Development·Ornit Chiba-Falek, Michael W Lutz
Feb 14, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Kacie D DetersLisa L Barnes

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Methods Mentioned

BETA
genotyping
PCR
electrophoresis
electrophoretic assay

Software Mentioned

GeneMapper
Ensembl
SDS

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