Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0030994
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dc.titleCharacterization of the poly-t variant in the tomm40 gene in diverse populations
dc.contributor.authorLinnertz C.
dc.contributor.authorSaunders A.M.
dc.contributor.authorLutz M.W.
dc.contributor.authorCrenshaw D.M.
dc.contributor.authorGrossman I.
dc.contributor.authorBurns D.K.
dc.contributor.authorWhitfield K.E.
dc.contributor.authorHauser M.A.
dc.contributor.authorMcCarthy J.J.
dc.contributor.authorUlmer M.
dc.contributor.authorAllingham R.
dc.contributor.authorWelsh-Bohmer K.A.
dc.contributor.authorRoses A.D.
dc.contributor.authorChiba-Falek O.
dc.date.accessioned2019-11-11T06:42:22Z
dc.date.available2019-11-11T06:42:22Z
dc.date.issued2012
dc.identifier.citationLinnertz C., Saunders A.M., Lutz M.W., Crenshaw D.M., Grossman I., Burns D.K., Whitfield K.E., Hauser M.A., McCarthy J.J., Ulmer M., Allingham R., Welsh-Bohmer K.A., Roses A.D., Chiba-Falek O. (2012). Characterization of the poly-t variant in the tomm40 gene in diverse populations. PLoS ONE 7 (2) : e30994. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0030994
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/162001
dc.description.abstractWe 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, respectively). In African-Americans, the frequency of the L-allele (0.10) is similar to Whites and Hispanics; however, the S-allele is more prevalent (0.65) and the VL-allele is concomitantly less frequent (0.25). The allele frequencies determined using the new methodology are compared to previous reports for Ghanaian, Japanese, Korean and Han Chinese cohorts. Finally, we studied the linkage pattern between TOMM40-'523' and APOE alleles. In Whites and Hispanics, consistent with previous reports, the L is primarily linked to ?4, while the majority of the VL and S are linked to ?3. Interestingly, in African-Americans, Ghanaians and Japanese, there is an increased frequency of the '523'S-APOE?4 haplotype. These data may be used as references for '523' allele and '523'-APOE haplotype frequencies in diverse populations for the design of research studies and clinical trials. © 2012 Linnertz et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectthymidine
dc.subjectapolipoprotein E
dc.subjectcarrier protein
dc.subjectpolythymidylic acid
dc.subjectTOMM40 protein, human
dc.subjectAfrican American
dc.subjectarticle
dc.subjectcapillary electrophoresis
dc.subjectCaucasian
dc.subjectChinese
dc.subjectcontrolled study
dc.subjectethnic difference
dc.subjectgene
dc.subjectgene frequency
dc.subjectgene number
dc.subjectgenetic polymorphism
dc.subjectgenetic variability
dc.subjectgenomic fragment
dc.subjectGhana
dc.subjecthaplotype
dc.subjectHispanic
dc.subjecthuman
dc.subjectJapanese
dc.subjectKorea
dc.subjectmolecular weight
dc.subjectpolymerase chain reaction
dc.subjecttranslocase of the outer mitochondrial membrane gene
dc.subjectAlzheimer disease
dc.subjectethnic and racial groups
dc.subjectethnic group
dc.subjectethnology
dc.subjectgenetics
dc.subjectgenotype
dc.subjectintron
dc.subjectprocedures
dc.subjectAlzheimer Disease
dc.subjectApolipoproteins E
dc.subjectEthnic Groups
dc.subjectGene Frequency
dc.subjectGenotype
dc.subjectHaplotypes
dc.subjectHumans
dc.subjectIntrons
dc.subjectMembrane Transport Proteins
dc.subjectMethods
dc.subjectPoly T
dc.subjectPopulation Groups
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1371/journal.pone.0030994
dc.description.sourcetitlePLoS ONE
dc.description.volume7
dc.description.issue2
dc.description.pagee30994
dc.published.statePublished
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