Short hypervariable microhaplotypes: A novel set of very short high discriminating power loci without stutter artefacts

Molecular Technology and Informatics for Personalised Medicine and Healt

FDSTools: A software package for analysis of massively parallel sequencing data with the ability to recognise and correct STR stutter and other PCR or sequencing noise

Molecular Technology and Informatics for Personalised Medicine and Healt

The Dutch Y-chromosomal landscape

Previous studies indicated existing, albeit limited, genetic-geographic population substructure in the Dutch population based on genome-wide data and a lack of this for mitochondrial SNP based data. Despite the aforementioned studies, Y-chromosomal SNP data from the Netherlands remain scarce and do not cover the territory of the Netherlands well enough to allow a reliable investigation of genetic-geographic population substructure. Here we provide the first substantial dataset of detailed spatial Y-chromosomal haplogroup information in 2085 males collected across the Netherlands and supplemented with previously published data from northern Belgium. We found Y-chromosomal evidence for genetic-geographic population substructure, and several Y-haplogroups demonstrating significant clinal frequency distributions in different directions. By means of prediction surface maps we could visualize (complex) distribution patterns of individual Y-haplogroups in detail. These results highlight the value of a micro-geographic approach and are of great use for forensic and epidemiological investigations and our understanding of the Dutch population history. Moreover, the previously noted absence of genetic-geographic population substructure in the Netherlands based on mitochondrial DNA in contrast to our Y-chromosome results, hints at different population histories for women and men in the Netherlands.Molecular Technology and Informatics for Personalised Medicine and Healt

Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic Clades in the Lion (Panthera leo)

Comparative phylogeography of African savannah mammals shows a congruent pattern in which populations in West/Central Africa are distinct from populations in East/Southern Africa. However, for the lion, all African populations are currently classified as a single subspecies (Panthera leo leo), while the only remaining population in Asia is considered to be distinct (Panthera leo persica). This distinction is disputed both by morphological and genetic data. In this study we introduce the lion as a model for African phylogeography. Analyses of mtDNA sequences reveal six supported clades and a strongly supported ancestral dichotomy with northern populations (West Africa, Central Africa, North Africa/Asia) on one branch, and southern populations (North East Africa, East/Southern Africa and South West Africa) on the other. We review taxonomies and phylogenies of other large savannah mammals, illustrating that similar clades are found in other species. The described phylogeographic pattern is considered in relation to large scale environmental changes in Africa over the past 300,000 years, attributable to climate. Refugial areas, predicted by climate envelope models, further confirm the observed pattern. We support the revision of current lion taxonomy, as recognition of a northern and a southern subspecies is more parsimonious with the evolutionary history of the lion.Netherlands Organization for Scientific Research (NWO) (project no. 820.01.002)

特集 生活習慣病

Molecular Technology and Informatics for Personalised Medicine and Healt

Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats

Peer reviewe

Development of forensic genomics research toolkits by the use of Massively Parallel Sequencing

Currently, Forensic DNA research is conducted almost exclusively using capillary electrophoresis to determine the length of fragments containing Short Tandem Repeats (STRs). Over the past decade, developments in MPS (Massively Parallel Sequencing techniques, also known as Next Generation Sequencing) offered new possibilities for forensic DNA research. This thesis focusses on the preparation, validation and implementation of MPS and the accompanying data analysis. By MPS, the exact DNA sequence of STRs is determined often revealing additional variation on top of the fragment length resulting in an even more unique DNA profile. Sequence information provides more insight on the DNA molecules comprising a conventional DNA profile. With this information, a software could be developed to make a better distinction between genuine alleles and noise offering possibilities for analysis of unbalanced DNA mixtures which are often encountered in forensic casework.As alternative DNA marker to STRs, research was conducted to select microhaplotypes (multiple variable positions in a small fragment). The statistical power of a profile generated from these microhaplotypes turned out to be almost as strong as that of STRs without suffering from the known STR-artefacts thereby offering possibilities for interpretation of DNA mixtures. </p

Development of forensic genomics research toolkits by the use of Massively Parallel Sequencing

Currently, Forensic DNA research is conducted almost exclusively using capillary electrophoresis to determine the length of fragments containing Short Tandem Repeats (STRs). Over the past decade, developments in MPS (Massively Parallel Sequencing techniques, also known as Next Generation Sequencing) offered new possibilities for forensic DNA research. This thesis focusses on the preparation, validation and implementation of MPS and the accompanying data analysis. By MPS, the exact DNA sequence of STRs is determined often revealing additional variation on top of the fragment length resulting in an even more unique DNA profile. Sequence information provides more insight on the DNA molecules comprising a conventional DNA profile. With this information, a software could be developed to make a better distinction between genuine alleles and noise offering possibilities for analysis of unbalanced DNA mixtures which are often encountered in forensic casework.As alternative DNA marker to STRs, research was conducted to select microhaplotypes (multiple variable positions in a small fragment). The statistical power of a profile generated from these microhaplotypes turned out to be almost as strong as that of STRs without suffering from the known STR-artefacts thereby offering possibilities for interpretation of DNA mixtures. LUMC / Geneeskund

Improved analysis of long STR amplicons from degraded single source and mixed DNA

Genomics, epigenetics, population genetics and bioinformatic

Cognitive-behavioural therapy for persistent and recurrent psychosis in people with schizophrenia-spectrum disorder: cost-effectiveness analysis

BACKGROUND: Evidence on cost-effectiveness is important to make well-informed decisions regarding care delivery. AIMS: To determine the balance between costs and health outcomes of cognitive-behavioural therapy (CBT) compared with treatment as usual (TAU) in people with schizophrenia who have persistent and recurrent symptoms of psychosis. Trial number: ISRCTN57292778. METHOD: A total of 216 people were randomised and followed up for 18 months. The primary clinical outcome measure was time functioning within the normal range. Normal functioning was defined as social functioning within the 95% range of the general population and no or minimal suffering and/or no or minimal affect on daily life of persistent psychotic symptoms. The difference in number of days was estimated. Using a societal perspective, cost differences were estimated and combined with clinical outcome to yield an incremental cost-effectiveness ratio (ICER). Uncertainty was accessed using bootstrapping and displayed by means of a cost-effectiveness acceptability curve. RESULTS: In the CBT group, participants experienced 183 days of normal social functioning, whereas the TAU group experienced 106 days. The ICER was euro47 per day of normal functioning gained. Cognitive-behavioural therapy implies higher costs, yet results in better health outcomes. Sensitivity analyses showed that targeting individuals who have not been hospitalised before receiving CBT results in an ICER of euro14 per day normal functioning gained. CONCLUSIONS: Days of normal functioning improved in the CBT condition compared with TAU, but this gain in health was associated with additional societal costs