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https://doi.org/10.1371/journal.pone.0030994
Title: | Characterization of the poly-t variant in the tomm40 gene in diverse populations | Authors: | Linnertz 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. |
Keywords: | thymidine apolipoprotein E carrier protein polythymidylic acid TOMM40 protein, human African American article capillary electrophoresis Caucasian Chinese controlled study ethnic difference gene gene frequency gene number genetic polymorphism genetic variability genomic fragment Ghana haplotype Hispanic human Japanese Korea molecular weight polymerase chain reaction translocase of the outer mitochondrial membrane gene Alzheimer disease ethnic and racial groups ethnic group ethnology genetics genotype intron procedures Alzheimer Disease Apolipoproteins E Ethnic Groups Gene Frequency Genotype Haplotypes Humans Introns Membrane Transport Proteins Methods Poly T Population Groups |
Issue Date: | 2012 | Citation: | Linnertz 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 | Rights: | Attribution 4.0 International | 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, 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. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/162001 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0030994 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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