23 research outputs found
The genetic study of three population microisolates in South Tyrol (MICROS): study design and epidemiological perspectives
<p>Abstract</p> <p>Background</p> <p>There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries.</p> <p>Methods</p> <p>The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken.</p> <p>Results</p> <p>Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%.</p> <p>Conclusion</p> <p>The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.</p
Stable population structure in Europe since the Iron Age, despite high mobility
Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000–3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire’s mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history
FALDOI: a new minimization strategy for large displacement variational optical flow
We propose a large displacement optical flow method that introduces a new strategy to compute a good local minimum of any optical flow energy functional. The method requires a given set of discrete matches, which can be extremely sparse, and an energy functional which locally guides the interpolation from those matches. In particular, the matches are used to guide a structured coordinate descent of the energy functional around these keypoints. It results in a two-step minimization method at the finest scale which is very robust to the inevitable outliers of the sparse matcher and able to capture large displacements of small objects. Its benefits over other variational methods that also rely on a set of sparse matches are its robustness against very few matches, high levels of noise, and outliers. We validate our proposal using several optical flow variational models. The results consistently outperform the coarse-to-fine approaches and achieve good qualitative and quantitative performance on the standard optical flow benchmarks.The first, second, and third authors acknowledge partial support by MICINN project, reference MTM2012-30772, by TIN2015-70410-C2-1-R (MINECO/FEDER, UE) and by GRC reference 2014 SGR 1301, Generalitat de Catalunya, and the fourth author by the European Research Council (advanced Grant Twelve Labours), Office of Naval research (ONR Grant N00014-14-1-0023)