An FPT haplotyping algorithm on pedigrees with a small number of sites

<p>Abstract</p> <p>Background</p> <p>Genetic disease studies investigate relationships between changes in chromosomes and genetic diseases. Single haplotypes provide useful information for these studies but extracting single haplotypes directly by biochemical methods is expensive. A computational method to infer haplotypes from genotype data is therefore important. We investigate the problem of computing the minimum number of recombination events for general pedigrees with a small number of sites for all members.</p> <p>Results</p> <p>We show that this NP-hard problem can be parametrically reduced to the Bipartization by Edge Removal problem with additional parity constraints. We solve this problem with an exact algorithm that runs in <inline-formula><graphic file="1748-7188-6-8-i1.gif"/></inline-formula> time, where <it>n </it>is the number of members, <it>m </it>is the number of sites, and <it>k </it>is the number of recombination events.</p> <p>Conclusions</p> <p>This algorithm infers haplotypes for a small number of sites, which can be useful for genetic disease studies to track down how changes in haplotypes such as recombinations relate to genetic disease.</p

High Expression Levels of Total IGF-1R and Sensitivity of NSCLC Cells In Vitro to an Anti-IGF-1R Antibody (R1507)

© 2009 Gong et al

Haplotype inference in general pedigrees with two sites

<p>Abstract</p> <p>Background</p> <p>Genetic disease studies investigate relationships between changes in chromosomes and genetic diseases. Single haplotypes provide useful information for these studies but extracting single haplotypes directly by biochemical methods is expensive. A computational method to infer haplotypes from genotype data is therefore important. We investigate the problem of computing the minimum number of recombination events for general pedigrees with two sites for all members.</p> <p>Results</p> <p>We show that this NP-hard problem can be parametrically reduced to the Bipartization by Edge Removal problem and therefore can be solved by an <it>O</it>(2<it>^k</it> · <it>n</it>²) exact algorithm, where <it>n</it> is the number of members and <it>k</it> is the number of recombination events.</p> <p>Conclusions</p> <p>Our work can therefore be useful for genetic disease studies to track down how changes in haplotypes such as recombinations relate to genetic disease.</p

On the complexity of resource-bounded logics

We revisit decidability results for resource-bounded logics and use decision problems for vector addition systems with states (VASS) to characterise the complexity of (decidable) model-checking problems. We show that the model-checking problem for the logic RB+-ATL is 2EXPTIME-complete by using recent results on alternating VASS. In addition, we establish that the model-checking problem for RBTL is decidable and has the same complexity as for RBTL* (the extension of RBTL with arbitrary path formulae), namely EXPSPACE-complete, proving a new decidability result as a by-product of the approach. Finally, we establish that the model-checking problem for RB+-ATL* is decidable by a reduction to parity games, and show how to synthesise values for resource parameters

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function

The concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) influenced the association between CR contributors and cognitive function in older adults. We show that BDNF Val66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers. APOE polymorphisms were not linked to the influence of CR on cognitive function. This result implicates BDNF in having an important role in capacity for building or accessing CR