List of Titles

Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD Searching for an effect of allelic heterogeneity

- Tovo-Rodrigues, Luciana, Rohde, Luis, Roman, Tatiana, Schmitz, Marcelo, Polanczyk, Guilherme, Zeni, Cristian, Marques, Francine, Contini, Veronica, Grevet, Eugenio, Belmonte-De-Abreu, Paulo, Bau, Claiton, Hutz, Mara

Authors: Tovo-Rodrigues, Luciana , Rohde, Luis , Roman, Tatiana , Schmitz, Marcelo , Polanczyk, Guilherme , Zeni, Cristian , Marques, Francine , Contini, Veronica , Grevet, Eugenio , Belmonte-De-Abreu, Paulo , Bau, Claiton , Hutz, Mara
Date: 2012
Type: Text , Journal article
Relation: Molecular Psychiatry Vol. 17, no. 5 (May 2012), p. 520-526
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Description: Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/ hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P = 0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P = 0.008 for total substitutions and P = 0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.
Description: C1

A multi-omics glimpse into the biology of arterial stiffness

- Eales, James, Romaine, Simon, Charchar, Fadi, Tomaszewski, Maciej

Authors: Eales, James , Romaine, Simon , Charchar, Fadi , Tomaszewski, Maciej
Date: 2015
Type: Text , Journal article
Relation: Journal of Hypertension Vol. 34, no. 1 (2015), p. 32-35
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Description: It has long been recognized that the structure of arteries throughout the vascular tree is not uniform. Notably, the media of large proximal (central) vessels contains relatively much greater amounts of elastin and elastic lamellae than smaller, more distal (peripheral) arteries; the converse is true of vascular smooth muscle cells. Under physiological conditions, the greater elasticity of central arteries compared with more muscular peripheral arteries allows conversion of the pulsatile nature of ventricular ejection into a relatively steady flow of blood at the distal end of the arterial system, conferring protection from pulsatile energy [1,2]. Furthermore, these differences in impedance can generate partial wave reflections, which arrive in the aorta during diastole, boosting diastolic blood pressure and augmenting coronary perfusion pressure [3].

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Undiagnosed cryptic diversity in small, microendemic frogs (Leptolalax) from the Central Highlands of Vietnam

- Rowley, Jodi, Tran, Dao, Frankham, Greta, Dekker, Anthony, Le, Duong, Nguyen, Truong, Dau, Vinh, Hoang, Huy

Authors: Rowley, Jodi , Tran, Dao , Frankham, Greta , Dekker, Anthony , Le, Duong , Nguyen, Truong , Dau, Vinh , Hoang, Huy
Date: 2015
Type: Text , Journal article
Relation: PLoS ONE Vol. 10, no. 5 (2015), p. 1-21
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Description: A major obstacle in prioritizing species or habitats for conservation is the degree of unrecognized diversity hidden within complexes of morphologically similar, "cryptic" species. Given that amphibians are one of the most threatened groups of organisms on the planet, our inability to diagnose their true diversity is likely to have significant conservation consequences. This is particularly true in areas undergoing rapid deforestation, such as Southeast Asia. The Southeast Asian genus Leptolalax is a group of small-bodied, morphologically conserved frogs that inhabit the forest-floor. We examined a particularly smallbodied and morphologically conserved subset, the Leptolalax applebyi group, using a combination of molecular, morphometric, and acoustic data to identify previously unknown diversity within. In order to predict the geographic distribution of the group, estimate the effects of habitat loss and assess the degree of habitat protection, we used our locality data to perform ecological niche modelling using MaxEnt. Molecular (mtDNA and nuDNA), acoustic and subtle morphometric differences revealed a significant underestimation of diversity in the L. applebyi group; at least two-thirds of the diversity may be unrecognised. Patterns of diversification and microendemism in the group appear driven by limited dispersal, likely due to their small body size, with several lineages restricted to watershed basins. The L. applebyi group is predicted to have historically occurred over a large area of the Central Highlands of Vietnam, a considerable portion of which has already been deforested. Less than a quarter of the remaining forest predicted to be suitable for the group falls within current protected areas. The predicted distribution of the L. applebyi group extends into unsurveyed watershed basins, each potentially containing unsampled diversity, some of which may have already been lost due to deforestation. Current estimates of amphibian diversity based on morphology alone are misleading, and accurate alpha taxonomy is essential to accurately prioritize conservation efforts. © 2015 Rowley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Isolated remnant or recent introduction? Estimating the provenance of Yellingbo Leadbeater's possums by genetic analysis and bottleneck simulation

- Hansen, Birgita, Taylor, Andrea

Authors: Hansen, Birgita , Taylor, Andrea
Date: 2008
Type: Text , Journal article
Relation: Molecular Ecology Vol. 17, no. 18 (2008), p. 4039-4052
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Description: Effective conservation management requires that genetically divergent populations potentially harbouring important local adaptations be identified and maintained as separate management units. In the case of the endangered Australian Leadbeater's possum (Gymnobelideus leadbeateri), an arboreal marsupial endemic to Victoria, uncertainty over the evolutionary origin of a potentially important extant wild population recently discovered in atypical habitat (lowland swamp) at Yellingbo is hampering such efforts. The population is rumoured to be a recent introduction. Microsatellite allele frequencies at Yellingbo differed substantially from those in sampled populations in montane ash forest (FST between 0.23 and 0.36), and Bayesian clustering analyses of genotypes strongly separated them (K = 2). We conducted a suite of bottlenecking tests which all indicated that Yellingbo had undergone a recent reduction in size. The extent to which the distinctiveness of Yellingbo animals might be expected solely through bottlenecking associated with a recent introduction, was tested by simulating population-history scenarios seeded with genotypes from candidate wild and captive sources. No bottleneck scenario reproduced anything approaching the genetic distinction of the Yellingbo population, with all structure analyses placing Yellingbo in a separate cluster to simulated populations (K = 2, minimum FST = 0.13). These results suggest that Yellingbo does not share recent ancestry with other extant populations and instead may be a remnant of an otherwise extinct gene pool. Importantly, this may include genes involved in adaptation to a lowland swamp environment, substantially adding to the conservation importance of this population, and suggesting that separate management may be prudent until evidence suggests otherwise. © 2008 The Authors.

Pathway analysis shows association between FGFBP1 and hypertension

- Tomaszewski, Maciej, Charchar, Fadi, Nelson, Christopher, Barnes, Timothy, Denniff, Matthew, Kaiser, Michael, Debiec, Radoslaw, Christofidou, Paraskevi, Rafelt, Suzanne, Van Harst, Pim Der, Wang, William, Maric, Christine, Zukowska-Szczechowska, Ewa, Samani, Nilesh

Authors: Tomaszewski, Maciej , Charchar, Fadi , Nelson, Christopher , Barnes, Timothy , Denniff, Matthew , Kaiser, Michael , Debiec, Radoslaw , Christofidou, Paraskevi , Rafelt, Suzanne , Van Harst, Pim Der , Wang, William , Maric, Christine , Zukowska-Szczechowska, Ewa , Samani, Nilesh
Date: 2011
Type: Text , Journal article
Relation: Journal of the American Society of Nephrology Vol. 22, no. 5 (2011), p. 947-955
Full Text: false
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Description: Variants in the gene encoding fibroblast growth factor 1 (FGF1) co-segregate with familial susceptibility to hypertension, and glomerular upregulation of FGF1 associates with hypertension. To investigate whether variants in other members of the FGF signaling pathway may also associate with hypertension, we genotyped 629 subjects from 207 Polish families with hypertension for 79 single nucleotide polymorphisms in eight genes of this network. Family-based analysis showed that parents transmitted the major allele of the rs16892645 polymorphism in the gene encoding FGF binding protein 1 (FGFBP1) to hypertensive offspring more frequently than expected by chance (P = 0.005). An independent cohort of 807 unrelated Polish subjects validated this association. Furthermore, compared with normotensive subjects, hypertensive subjects had approximately 1.5- and 1.4-fold higher expression of renal FGFBP1 mRNA and protein (P = 0.04 and P = 0.001), respectively. By immunohistochemistry, hypertensionrelated upregulation of FGFBP1 was most apparent in the glomerulus and juxtaglomerular space. Taken together, these data suggest that FGFBP1 associates with hypertension and that systematic analysis of signaling pathways can identify previously undescribed genetic associations. Copyright Â© 2011 by the American Society of Nephrology.

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