A Study of the Complex Genetic Inheritance of Lipids

Hart- en vaatziekten vormen wereldwijd de belangrijkste oorzaak van morbiditeit en mortaliteit. Risicofactoren voor hart- en vaatziekten zijn vier typen circulerende lipide levels: high-density lipoproteïne cholesterol (HLD-C), low-density lipoproteïne cholesterol (LDL-C), totaal cholesterol (TC) en triglyceriden (TG). Deze vier typen circulerende lipide levels zijn in hoge mate erfelijk. Ondanks het vele onderzoek dat is gedaan naar circulerende lipide levels, is de meeste genetische variatie die de hoge erfelijkheid bepaald, nog steeds grotendeels onbekend. In dit proefschrift streef ik ernaar nieuwe variaties te ontdekken die geassocieerd kunnen worden met circulerende lipide levels. Daarvoor gebruikte ik meerdere genetische epidemiologische benaderingen: GWAS, genoomwijde interactie studies (GWIS) en exoomwijde associatie studies (ExWAS). GWAS heb ik toegepast op genoom-data van individuals die geimputeerd zijn met ofwel het Genoom van Nederland referentie panel ofwel het 1000 Genomes referentie panel. Deze individuen zijn deels afkomstig uit populatie gebaseerde cohorten en deels afkomstig uit familie gebaseerde cohorten. De hypothese vrije GWIS benadering was enkel toegepast op de Rotterdam Study, een lopende studie en de ExWAS benadering werd toegepast op een geisoleerde familie gebaseerde populatie. Alle methodes hebben nieuwe variaties gevonden die geassocieerd zijn met lipiden. Enkele varianten beinvloeden de functie en het structuur van het eiwit en hebben dus grote effecten en zijn daarom mogelijk nieuwe targets voor farmaceutische middelen

Mid- and late-Holocene vegetation and fire history at Biviere di Gela, a coastal lake in southern Sicily, Italy

The vegetation and fire history of few coastal sites has been investigated in the Mediterranean region so far. We present the first paleoecological reconstruction from coastal Sicily, the largest island in the Mediterranean Sea. We analysed pollen and charcoal in the sediments of Biviere di Gela, a lake (lagoon) on the south coast of Sicily. Our data suggest that the area became afforested after a marine transgression at ca. 7200 cal b.p. (5250 b.c.). Build-up of forest and shrublands took ca. 200-300years, mainly with the deciduous trees Quercus, Ostrya and Fraxinus. Juniperus expanded ca. 6900 cal b.p. (4950 b.c.), but declined again 6600 cal b.p. (4650 b.c.). Afterwards, evergreen trees (Q. ilex-type and Olea) became dominant in the forest and Pistacia shrublands were established. Forest and shrubland reached a maximum ca. 7000-5000 cal b.p. (5050-3050 b.c.); subsequently forest declined in response to human impact, which was probably exacerbated by a general trend towards a more arid climate. During the Neolithic, fire was used to open the landscape, significantly reducing several arboreal taxa (Q. ilex, Fraxinus, Juniperus) and promoting herbs and shrubs (Achillea, Cichorioideae, Brassicaceae, Ephedra). Final forest disruption occurred around 2600 cal b.p. (650 b.c.) with the onset of the historically documented Greek colonization. We conclude that the open maquis and garrigue vegetation of today is primarily the consequence of intensive land-use over millennia. Under natural or near-natural conditions arboreal taxa such as Q. ilex, Olea and Pistacia would be far more important than they are today, even under the hot and rather dry coastal conditions of southern Sicil

Varietal responses to soil water deficit: first results from a common-garden vineyard near Bordeaux France

In wine producing regions around the world, climate change has the potential to decrease the frequency and amount of precipitation and increase average and extreme temperatures. This will both lower soil water availability and increase evaporative demand in vineyards, thereby increasing soil water deficits and associated vine stress. Grapevines control their water status by regulating stomatal closure and other changes to internal plant hydraulics. These responses are complex and have not been clearly characterized across a wide range of different Vitis vinifera varieties. Understanding how vine water status responds to changes in soil water deficits and other variables will help growers modify vineyard design and management practices to meet their quality and yield objectives. Carbon isotope discrimination measurements of certain plant tissues have been shown to provide effective characterization of stomatal closure, while water potential measurements provide a well-proven measure of overall vine water status. Using replicated data collected from an experimental common-garden vineyard at the Institut des Sciences de la Vigne et du Vin (ISVV) near Bordeaux, France, this project will analyze the effects on carbon isotope discrimination across 39 varieties and water potential across eight varieties against estimates of soil water deficits made using a water balance model running on local meteorology and considering the phenology of each variety. Similar to the literature, preliminary analysis finds as soil water deficit increases, carbon isotope data suggests greater stomatal closure and water potential measurements indicate greater vine stress. For both parameters, analysis will be performed to distinguish any difference in these responses between varieties

Soil type and soil preparation influence vine development and grape composition through its impact on vine water and nitrogen status

The influence of soil type and preparation on vine development and grape composition was investigated in a 50 ha estate located in Saint-Emilion (Bordeaux, France) and planted predominantly with Merlot. Part of the vineyard was planted down the slopes and another part of the vineyard was planted on terraces, where soils were profoundly modified through soil preparation. Grape composition (berry weight, sugar, total acidity, malic acid and pH), vigor (pruning weight), vine nitrogen status (Yeast Available Nitrogen (YAN) in grapes) and vine water status (δ13C) was measured at a very high density grid of 10 data points per hectare. Water deficit was globally weak over the estate because of high soil water holding capacity whereas vine nitrogen status was highly variable. Vine vigor and grape composition were predominantly driven by vine nitrogen status. On terraces, where soils were deep, due to invasive soil preparation, water deficits were particularly small or non-existent and vine nitrogen status was highly variable. Grape quality potential was medium to low, except in places with low nitrogen status, but at the expense of low yields. On parcels planted down the slopes water deficits were recorded because vine rooting was limited by compact subsoils. Vine nitrogen status was homogeneous. Grape quality and yield were medium to high and relatively homogeneous. When possible, downhill plantations are to be preferred over terraces because in the latter vine yield and quality parameters are highly variable because of massive soil movements prior to plantation

Palynological investigations reveal Eemian interglacial vegetation dynamics at Spiezberg, Bernese Alps, Switzerland

Interglacial pollen records are valuable archives of past vegetation dynamics and provide important information about vegetation responses to different-than-today climates. Interglacial pollen archives pre-dating the Last Glacial Maximum (LGM) are scarce on the Swiss Plateau in contrast to the many available Late Glacial and Holocene records. This is mainly due to the rapidly changing palaeo- environmental conditions throughout the Quaternary and the low preservation potential of material suitable for palynological investigations. The Spiezberg site offers a palynological record situated most proximal to the Alps in Switzerland. Previous investigations tentatively assigned this record to the Eemian interglacial (MIS 5e). We have conducted additional pollen analytical investigations to increase the quantity of pollen information. Besides biostratigraphic interpretations, we use numerical methods such as distance analysis (distantia) and ordination techniques (PCA) to evaluate the similarities and differences between the Spiezberg record and its geographically and chronostratigraphically closest physically dated (U/Th, luminescence) analogues from the Eemian (MIS 5e) and Meikirch 3 (MIS 7a) interglacials. Our palynological investigations reveal the predominance of closed temperate forests with abundant fir (Abies) and spruce (Picea) as well as evergreen broad-leaved taxa (e.g. Hedera). The attri- bution to the Eemian interglacial relies on the observation of very rare beech (Fagus) occurrences, a phase with prominent yew (Taxus) and the unimportance of hornbeam (Carpinus), all of which are typical Eemian features on the Swiss Plateau. An Eemian age is supported by the numerical comparison with the Beerenmo€sli (MIS 5e) and Meikirch 3 (MIS 7a) reference records. Furthermore, the Picea, Taxus and Fagus dynamics observed on the Swiss Plateau during the Eemian are in excellent agreement with vegetational patterns observed elsewhere in Central Europe. Surprisingly, Carpinus was almost absent on the Swiss Plateau during the Eemian, whereas it was a major component of the forest at other European sites with a similar elevation as Spiezberg. We explain this by environmental conditions and the strong competition with Abies alba. In particular, considering the European Eemian vegetation history and the results of our reconstructions from the Swiss Plateau, we find that Abies alba was a highly competitive tree under natural warmer-than-today conditions. This finding provides further evidence that Abies alba may benefit from future climate warming

Moving towards grapevine genotypes better adapted to abiotic constraints

Vitis spp., both in their cultivated and wild forms, have been growing in a large diversity of environments for thousands of years. As a result, they have developed many adaptive mechanisms controlled by a range of regulatory processes. The cultivated species, Vitis vinifera, is quite well adapted to semi-arid conditions and its cultivation can be used to produce crops on marginal lands. However, this is threatened by climate change, which is associated with increased temperature and CO2 atmospheric content, changes in water availability and an increased likelihood of extreme events, such as heat waves and early spring frosts. Indirect effects of climate change on solar radiation and soil minerals are also expected. Consequently, cultivated grapevines will presumably face more abiotic constraints occurring concomitantly or successively over one or more growing cycles. In addition to climate change, worldwide viticulture must reduce the use of pesticides. Adapting to climate change and reducing pesticide use are challenging, and increase the need to create new grapevine varieties that are more resistant to diseases and better adapted to abiotic constraints. For this purpose, the adaptive mechanisms of wild and cultivated Vitis spp. must be exploited. While major advances have already been made in exploiting wild alleles for disease resistance, the polygenic nature of adaptation to abiotic factors has slowed down research progress. To tackle this limitation, ambitious integrative strategies need to be undertaken from collection and characterization of genetic resources, investigations on genetic architecture and identification of underlying genes (including those involved in epigenetic regulation), to the implementation of new breeding technologies and the development of genomic selection. An update on the state-of-the-art regarding these aspects is presented

Using δ13C and hydroscapes for discriminating cultivar specific drought responses

This article is published in cooperation with Terclim 2022 (XIVth International Terroir Congress and 2nd ClimWine Symposium), 3-8 July 2022, Bordeaux, France.Measurement of carbon isotope discrimination in berry juice at maturity (δ13C) provides an integrated assessment of vine water status and water use efficiency (WUE) during the period of berry ripening, and when collected over multiple seasons, can provide an indication of drought stress responses. Berry juice δ13C measurements were carried out on 48 different varieties planted in a common garden experiment in Bordeaux, France from 2014 through 2020 and found important differences across this large panel of varieties. Cluster analysis showed that δ13C values are likely affected by the differing phenology of each variety, resulting in berry ripening of different varieties taking place under different conditions of soil water availability within the same year. Accounting for these phenological differences, the cluster analysis created a classification of varieties that corresponds well to our current empirical understanding of their relative drought tolerance. In addition, using measurements of predawn and midday leaf water potential measurements collected over four seasons on a subset of six varieties, a hydroscape approach was used to develop a list of metrics indicative of the sensitivity of stomatal regulation to water stress (i.e., an/isohydric behaviour). Key hydroscape metrics were also found to be well correlated with some δ13C metrics. A variety’s water potential regulation as characterized by a minimum critical leaf water potential as determined from hydroscapes was strongly correlated to δ13C values under well-watered conditions, suggesting that the latter may be a useful indicator of drought stress response.COntinental To coastal Ecosystems: evolution, adaptability and governanc

Population-specific genotype imputations using minimac or IMPUTE2

In order to meaningfully analyze common and rare genetic variants, results from genome-wide association studies (GWASs) of multiple cohorts need to be combined in a meta-analysis in order to obtain enough power. This requires all cohorts to have the same single-nucleotide polymorphisms (SNPs) in their GWASs. To this end, genotypes that have not been measured in a given cohort can be imputed on the basis of a set of reference haplotypes. This protocol provides guidelines for performing imputations

Holocene vegetation and fire history of the mountains of Northern Sicily (Italy)

Knowledge about vegetation and fire history of the mountains of Northern Sicily is scanty. We analysed five sites to fill this gap and used terrestrial plant macrofossils to establish robust radiocarbon chronologies. Palynological records from Gorgo Tondo, Gorgo Lungo, Marcato Cixé, Urgo Pietra Giordano and Gorgo Pollicino show that under natural or near natural conditions, deciduous forests (Quercus pubescens, Q. cerris, Fraxinus ornus, Ulmus), that included a substantial portion of evergreen broadleaved species (Q. suber, Q. ilex, Hedera helix), prevailed in the upper meso- mediterranean belt. Mesophilous deciduous and evergreen broadleaved trees (Fagus sylvatica, Ilex aquifolium) dominated in the natural or quasi-natural forests of the oro- mediterranean belt. Forests were repeatedly opened for agricultural purposes. Fire activity was closely associated with farming, providing evidence that burning was a primary land use tool since Neolithic times. Land use and fire activity intensified during the Early Neolithic at 5000 bc, at the onset of the Bronze Age at 2500 bc and at the onset of the Iron Age at 800 bc. Our data and previous studies suggest that the large majority of open land communities in Sicily, from the coastal lowlands to the mountain areas below the thorny-cushion Astragalus belt (ca. 1,800 m a.s.l.), would rapidly develop into forests if land use ceased. Mesophilous Fagus-Ilex forests developed under warm mid Holocene conditions and were resilient to the combined impacts of humans and climate. The past ecology suggests a resilience of these summer-drought adapted communities to climate warming of about 2 °C. Hence, they may be particularly suited to provide heat and drought-adapted Fagus sylvatica ecotypes for maintaining drought-sensitive Central European beech forests under global warming conditions

Estimating Bulk Stomatal Conductance in Grapevine Canopies

In response to changes in their environments, grapevines regulate transpiration using various physiological mechanisms that alter conductance of water through the soil-plant-atmosphere continuum. Expressed as bulk stomatal conductance at the canopy scale, it varies diurnally in response to changes in vapor pressure deficit and net radiation, and over the season to changes in soil water deficits and hydraulic conductivity of both the soil and plant. To help with future characterization of this dynamic response, a simplified method is presented for determining bulk stomatal conductance based on the crop canopy energy flux model by Shuttleworth and Wallace using measurements of individual vine sap flow, temperature and humidity within the vine canopy, and estimates of net radiation absorbed by the vine canopy. The methodology presented respects the energy flux dynamics of vineyards with open canopies, while avoiding problematic measurements of soil heat flux and boundary layer conductance needed by other methods, which might otherwise interfere with ongoing vineyard management practices. Based on this method and measurements taken on several vines in a non-irrigated vineyard in Bordeaux France, bulk stomatal conductance was estimated on 15-minute intervals from July to mid-September 2020 producing values similar to those presented for vineyards in the literature. Time-series plots of this conductance show significant diurnal variation and seasonal decreases in conductance associated with increased vine water stress as measured by predawn leaf water potential. Global sensitivity analysis using non-parametric regression found transpiration flux and vapor pressure deficit to be the most important input variables to the calculation of bulk stomatal conductance, with absorbed net radiation and bulk boundary layer conductance being much less important. Conversely, bulk stomatal conductance was one of the most important inputs when calculating vine transpiration, emphasizing the usefulness of characterizing its dynamic response for the purpose of estimating vine canopy transpiration in water use models.COntinental To coastal Ecosystems: evolution, adaptability and governanc