The quantitative trait linkage disequilibrium test: a more powerful alternative to the quantitative transmission disequilibrium test for use in the absence of population stratification

Linkage analysis based on identity-by-descent allele-sharing can be used to identify a chromosomal region harboring a quantitative trait locus (QTL), but lacks the resolution required for gene identification. Consequently, linkage disequilibrium (association) analysis is often employed for fine-mapping. Variance-components based combined linkage and association analysis for quantitative traits in sib pairs, in which association is modeled as a mean effect and linkage is modeled in the covariance structure has been extended to general pedigrees (quantitative transmission disequilibrium test, QTDT). The QTDT approach accommodates data not only from parents and siblings, but also from all available relatives. QTDT is also robust to population stratification. However, when population stratification is absent, it is possible to utilize even more information, namely the additional information contained in the founder genotypes. In this paper, we introduce a simple modification of the allelic transmission scoring method used in the QTDT that results in a more powerful test of linkage disequilibrium, but is only applicable in the absence of population stratification. This test, the quantitative trait linkage disequilibrium (QTLD) test, has been incorporated into a new procedure in the statistical genetics computer package SOLAR. We apply this procedure in a linkage/association analysis of an electrophysiological measurement previously shown to be related to alcoholism. We also demonstrate by simulation the increase in power obtained with the QTLD test, relative to the QTDT, when a true association exists between a marker and a QTL.     

Fine mapping of a quantitative trait locus (QTL) from Lycopersicon hirsutum chromosome 1 affecting fruit characteristics and agronomic traits: breaking linkage among QTLs affecting different traits and dissection of heterosis for yield

The near-isogenic Line TA523, containing a 40-cM introgression at the bottom of chromosome 1 from Lycopersicon hirsutum acc. LA1777, affects several agronomically important traits. A set of recombinant lines (subNILs) derived from the original NIL TA523 were developed in order to fine-map, by substitution mapping, the genetic factors included within the original introgression. In the current experiment, TA523 showed redder, rounded, less pigmented shoulder, lower-weighted fruits and higher brix, whereas higher yield and brix*yield was observed only in the hybrid TA253×TA209 suggesting heterosis for these traits. By substitution mapping we mapped independent genetic loci affecting brix, yield and fruit shape, whereas fruit weight, shoulder pigmentation and external color mapped to a position coincident with the brix locus. Analysis of the subNILs revealed that the gene action of most of the QTLs was additive or nearly additive. The exception was for the yield QTL which was dominant (d/a=0.7), eliminating the possibility that yield increase is due to true overdominance at a single gene locus. However, no negative yield effects were detected in other regions of the introgressed segment, as would be predicted by a dominance complementation model. Therefore, epistatic interactions among genetic factors along the introgressed segment are suggested as the cause of yield heterosis. Results from this study, combined with previous experiments involving different tomato wild species, demonstrate that the base of chromosome 1 of tomato contains multiple QTLs affecting various agronomic and fruit traits and that these effects can not be attributed to the pleiotropic effects of a single locus. Received: 21 April 1999 / Accepted: 17 June 1999     

“Decoding the Dots”: The ImageStream system (ISS) as a novel and powerful tool for flow cytometric analysis

The aim of this article is to provide a brief review of the ImageStream system (ISS). The ISS technology was developed as a novel method for multiparameter cell analysis and subsequently as a supportive tool for flow cytometry (FC). ISS integrates the features of FC and fluorescent microscopy collecting images of acquired cells for offline digital image analysis. The article presents an overview of the main characteristics of ISS and a comparison between ISS, FC and the laser scanning cytometer (LSC). We reviewed ISS applications focusing on those involved in cellular phenotyping and provide our own experience with using ISS as a supportive tool to classical FC and demonstrate the compatibility between FC and ISS photometric analysis as well as the advantages of using ISS to confirm FC results.     

The Duffy binding protein as a key target for a Plasmodium vivax vaccine: lessons from the Brazilian Amazon

Plasmodium vivax infects human erythrocytes through a major pathwaythat requires interaction between an apical parasite protein, the Duffy bindingprotein (PvDBP) and its receptor on reticulocytes, the Duffy antigen/receptor forchemokines (DARC). The importance of the interaction between PvDBP (region II, DBPII)and DARC to P. vivax infection has motivated our malaria researchgroup at Oswaldo Cruz Foundation (state of Minas Gerais, Brazil) to conduct a numberof immunoepidemiological studies to characterise the naturally acquired immunity toPvDBP in populations living in the Amazon rainforest. In this review, we provide anupdate on the immunology and molecular epidemiology of PvDBP in the BrazilianAmazon - an area of markedly unstable malaria transmission - andcompare it with data from other parts of Latin America, as well as Asia andOceania.     

The tree ring growth histories of UK native oaks as a tool for investigating Chronic Oak Decline: An example from the Forest of Dean

Declines are a distinctive category of tree disease, complex to define and quantify and challenging to mitigate due to their multiple causes and heterogeneous tree response patterns. In many parts of Europe oak decline syndromes are severely impacting tree health and having a measurable economic impact on forestry. In the UK the impact of periodic oak declines is expanding against a backdrop of multiple environmental pressures, to levels capable of threatening the UK’s native oak woodland. Here we explore the growth histories of oak trees at a site symptomatic of Chronic Oak Decline (COD), in the South of England; Speculation Cannop in the Forest of Dean, Gloucestershire. The dendrochronological picture at the site reveals that trees with current external COD symptoms have shown suppressed growth, in relation to the regional average, from early on in their lives. Moreover, there is an amplified reduction in minimum ring width in Symptomatic trees as compared to a healthy subsample of Control trees, likely to be heavily dominated by reduced latewood width in affected trees, as decline sets in. Broadly, the site reveals the initial appearance of decline, roughly 40 years after planting, in 1860. There is considerable variability in the later decline history pattern in Symptomatic trees but there are clusters of decline episodes in the 1920s, 1960s, 1980s and 1990s at this site. The Control trees are not always unaffected but rather show growth releases after each historical decline phase. The trees that currently show external decline symptoms do not have a history of these growth releases. We conclude that investigating the tree ring growth histories at sites impacted by COD could provide an important management tool, and ring width histories of trees at affected sites should be used in the identification of the decline predisposing factors, that a management strategy requires.