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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.

We have determined the radial velocities of the [O iii]-emitting gas in the inner narrow-line region of the Seyfert 2 galaxy NGC 1068, along a slit at position angle 202 degrees, from STIS observations at a spatial resolution of 0&farcs;1 and a spectral resolving power of lambda&solm0;Deltalambda approximately 1000. We use these data to investigate the kinematics of the narrow-line region within 6&arcsec; ( approximately 430 pc) of the nucleus. The emission-line knots show evidence for radial acceleration to a projected angular distance of 1&farcs;7 in most cases, followed by deceleration that approaches the systemic velocity at a projected distance of approximately 4&arcsec;. We find that a simple kinematic model of biconical radial outflow can match the general trend of observed radial velocities. In this model, the emitting material is evacuated along the bicone axis, and the axis is inclined 5 degrees out of the plane of the sky. The acceleration of the emission-line clouds provides support for dynamical models that invoke radiation and/or wind pressure. We suggest that the deceleration of the clouds is due to their collision with a patchy and anistropically distributed ambient medium.