Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations

We describe and test a Markov chain model of microsatellite evolution that can explain the different distributions of microsatellite lengths across different organisms and repeat motifs. Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes both strand slippage and point mutation events. We compute the stationary distribution of allele lengths under this model and use it to fit DNA data for di-, tri-, and tetranucleotide repeats in humans, mice, fruit flies, and yeast. The best fit results lead to slippage rate estimates that are highest in mice, followed by humans, then yeast, and then fruit flies. Within each organism, the estimates are highest in di-, then tri-, and then tetranucleotide repeats. Our estimates are consistent with experimentally determined mutation rates from other studies. The results suggest that the different length distributions among organisms and repeat motifs can be explained by a simple difference in slippage rates and that selective constraints on length need not be imposed.

Somatic mosaicism in Wiskott–Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism

Somatic mosaicism caused by in vivo reversion of inherited mutations has been described in several human genetic disorders. Back mutations resulting in restoration of wild-type sequences and second-site mutations leading to compensatory changes have been shown in mosaic individuals. In most cases, however, the precise genetic mechanisms underlying the reversion events have remained unclear, except for the few instances where crossing over or gene conversion have been demonstrated. Here, we report a patient affected with Wiskott–Aldrich syndrome (WAS) caused by a 6-bp insertion (ACGAGG) in the WAS protein gene, which abrogates protein expression. Somatic mosaicism was documented in this patient whose majority of T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage in vivo. Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same six nucleotides. These findings strongly suggest that DNA polymerase slippage was the cause of the original germ-line insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the propositus T cell progenitors, thus leading to reversion mosaicism.

Rolling resistance of tires measured under transient and equilibrium conditions on Calspan's tire research. Final report.

Transportation Department, Office of the Assistant Secretary for Systems Development and Technology, Washington, D.C.

Mechanics of pneumatic tires.

Mode of access: Internet.

Correlation between ultrasonic nondestructive inspection and wheel test of 34 retreaded tires. Interim report.

National Highway Traffic Safety Administration, Office of Research and Development, Washington, D.C.

Report of pre and post road test ultrasonic inspection results on 134 passenger tires: final report.

National Highway Traffic Safety Administration, Washington, D.C.

Rolling resistance of light truck tires. Final report.

National Highway Traffic Safety Administration, Office of Research and Development, Washington, D.C.

Research report on the physical condition of passenger vehicle tires in highway use. Final report.

National Bureau of Standards, Office of Vehicle Systems Research, Washington, D.C.

Equilibrium and transient rolling resistance of truck tires measured on Calspan's tire research facility. Final report.

Transportation Department, Office of Noise Abatement, Washington, D.C.

Results of energy-loss measurements on passenger car tires operating in the free-rolling and braking/traction modes. Final report.

Transportation Systems Center, Cambridge, Mass.

An experimental and analytical investigation of the vibration noise generation mechanism in truck tires. Interim report.

National Highway Traffic Safety Administration, Office of Heavy Duty Vehicle Research, Washington, D.C.

Safety related recall campaigns for motor vehicles and motor vehicle equipment, including tires, January 1, 1977 to December 31, 1977.

Mode of access: Internet.

Safety related recall campaigns for motor vehicles and motor vehicle equipment, including tires, January 1, 1978 to December 31, 1978.

Mode of access: Internet.