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Higham C.F.,United Medical Systems | Higham C.F.,Boyd Orr Center for Population and Ecosystem Health | Morales F.,United Medical Systems | Morales F.,University of Costa Rica | And 5 more authors.
Human Molecular Genetics | Year: 2012

Several human genetic diseases are associated with inheriting an abnormally large unstable DNA simple sequence repeat. These sequences mutate, by changing the number of repeats, many times during the lifetime of those affected, with a bias towards expansion. These somatic changes lead not only to the presence of cells with different numbers of repeats in the same tissue, but also produce increasingly longer repeats, contributing towards the progressive nature of the symptoms. Modelling the progression of repeat length throughout the lifetime of individuals has potential for improving prognostic information as well as providing a deeper understanding of the underlying biological process. A large data set comprising blood DNA samples from individuals with one such disease, myotonic dystrophy type 1, provides an opportunity to parameterize a mathematical model for repeat length evolution that we can use to infer biological parameters of interest. We developed new mathematical models by modifying a proposed stochastic birth process to incorporate possible contraction. A hierarchical Bayesian approach was used as the basis for inference, and we estimated the distribution of mutation rates in the population. We used model comparison analysis to reveal, for the first time, that the expansion bias observed in the distributions of repeat lengths is likely to be the cumulative effect of many expansion and contraction events. We predict that mutation events can occur as frequently as every other day, which matches the timing of regular cell activities such as DNA repair and transcription but not DNA replication. © The Author 2012. Published by Oxford University Press. All rights reserved. Source


Acosta-Jamett G.,Roslin Institute | Acosta-Jamett G.,UK Institute of Zoology | Acosta-Jamett G.,Austral University of Chile | Cleaveland S.,Boyd Orr Center for Population and Ecosystem Health | And 2 more authors.
Preventive Veterinary Medicine | Year: 2010

A cross-sectional household questionnaire survey was conducted along two transects (80 and 45 km long) from Coquimbo and Ovalle cities to the Fray Jorge National Park (FJNP) in the Coquimbo region of Chile in 2005-2007 to investigate the demography of dogs in the context of a study of canine infectious diseases. Data were collected on the number of dogs per household, fecundity, mortality, and sex and age distribution. The results from 1021 households indicated that dog ownership was common, with a higher proportion of households owning dogs in rural areas (89%), than in towns (63%) or cities (49%). Dog density ranged from 1380 ± 183 to 1509 ± 972 dogs km-2 in cities, from 119 ± 18 to 1544 ± 172 dogs km-2 in towns, and from 1.0 ± 0.4 to 15.9 ± 0.4 dogs km-2 in rural sites. The dog population was estimated to be growing at 20% in cities, 19% in towns and 9% in rural areas. The human:dog ratio ranged from 5.2 to 6.2 in cities, from 2.3 to 5.3 in towns, and from 1.1 to 2.1 in rural areas. A high percentage of owned dogs was always allowed to roam freely in the different areas (27%, 50% and 67% in cities, towns and rural areas, respectively). Observations of free-roaming dogs of unknown owner were reported from a greater proportion of respondents in cities (74%), followed by towns (51%) and finally by rural areas (21%). Overall only 3% of dogs had been castrated. In addition, only 29% of dogs were reported to have been vaccinated against canine distemper virus (CDV) and 30% against canine parvovirus (CPV). The higher population size and density, higher growth rate and a higher turnover of domestic dogs in urban than in rural areas and the poorly supervised and inadequately vaccinated dog populations in urban areas suggest that urban areas are more likely to provide suitable conditions for dogs to acts as reservoirs of pathogenic infections. © 2010 Elsevier B.V. Source

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