دورية أكاديمية
Characterization of the poly-T variant in the TOMM40 gene in diverse populations.
| العنوان: | Characterization of the poly-T variant in the TOMM40 gene in diverse populations. |
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| المؤلفون: | Colton Linnertz, Ann M Saunders, Michael W Lutz, Donna M Crenshaw, Iris Grossman, Daniel K Burns, Keith E Whitfield, Michael A Hauser, Jeanette J McCarthy, Megan Ulmer, Rand Allingham, Kathleen A Welsh-Bohmer, Allen D Roses, Ornit Chiba-Falek |
| المصدر: | PLoS ONE, Vol 7, Iss 2, p e30994 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | 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 ε4, while the majority of the VL and S are linked to ε3. Interestingly, in African-Americans, Ghanaians and Japanese, there is an increased frequency of the '523'S-APOEε4 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC3281049?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0030994 |
| URL الوصول: | https://doaj.org/article/f942e05d472a4d749d9caeb46a486e20 |
| رقم الأكسشن: | edsdoj.f942e05d472a4d749d9caeb46a486e20 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0030994 |