Positional identification of variants of Adamts16 linked to inherited hypertension

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling B

Positional identification of variants of Adamts16 linked to inherited hypertension

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling BP

Evolutionary, biogeographic, and population genetic relationships of dreissenid mussels, with revision of component taxa

The identification of taxa and discernment of evolutionary relationships within the family Dreissenidae have been confounded by morphological plasticity as well as prior lack of a comprehensive DNA sequence data analysis. We thus analyzed the phylogenetic relationships of putative taxa (species and subspecies) in the genus Dreissena in relation to its nearest living relatives (Mytilopsis leucophaeata and Congeria kusceri) using DNA sequence data from the nuclear 28S RNA gene and three mitochondrial genes: cytochrome c oxidase subunit I (COI), 16S RNA, and cytochrome (cyt) b oxidase. Relationships resolved by maximum likelihood and Bayesian phylogenetic trees are robust and congruent and support division of Dreissena into three subgenera: Dreissena, Pontodreissena, and Carinodreissena. The subgenus Pontodreissena contains two species: Dreissena caputlacus and Dreissena rostriformis. Putative subspecies once proposed for D. rostriformis lack genetic divergence and likely should no longer be recognized; these include D. r. “bugensis” (the quagga mussel), D. r. “grimmi,” D. r. “distincta,” and D. r. “compressa.” The Pontodreissena then comprises the sister group (nearest relative) to a clade comprising the other two subgenera (Dreissena and Carinodreissena). The subgenus Carinodreissena contains the valid taxa Dreissena carinata and Dreissena blanci; both inhabit ancient lakes in the Balkan Peninsula. We consider the once recognized Dreissena “stankovici” and Dreissena “presbensis” to be synonyms of Dreissena carinata; DNA and morphological evidence supports this conclusion. The subgenus Dreissena includes two species, Dreissena polymorpha and Dreissena anatolica. D. anatolica is endemic to Turkey in lakes north of the Mediterranean, and D. polymorpha (the zebra mussel) has been widely introduced throughout much of Eurasia and North America, spreading from its native distribution in the Pontocaspian region. We additionally analyze population genetic variation for invasive and native populations of the zebra mussel D. polymorpha (using 11 nuclear DNA microsatellite loci) and the quagga mussel D. r. “bugensis” (using 9 microsatellite loci) across North America and Eurasia and compare our results with previous studies that used other markers. Results reveal significant genetic structuring of introduced populations from Eurasia and North America for both species. North American invasions of both species were founded from multiple source populations and a large number of propagules, showing no founder effects and substantial genetic diversity. In contrast, recently colonized quagga mussel populations from the Colorado River and California exhibit some founder effects. Genetic compositions of both species have changed over time at given colonization sites, with some populations adding alleles from adjacent populations, some losing them, and most retaining closest similarity to their original composition. In conclusion, these genetic data comprise a valuable baseline for resolving present and future invasion pathways for dreissenids, as well as interpreting patterns of distributions in their native ecosystems. © 2014 by Taylor & Francis Group, LLC

Association of von Willebrand factor activity with ACE I/D and MTHFR C677T polymorphisms in migrainecha_1824 960..968

Angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) and methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphisms are linked to endot-helial dysfunction and to cerebral white matter lesions. Objectives of this study were to determine if ACE and MTHFR gene polymorphisms are associated with von Willebrand factor (vWF) activity, an endothelial dysfunction marker, and with a distinct headache phenotype. We enrolled 64 women (18–50 years old) with International Classification of Headache Disorders, 2nd edn migraine without aura (MoA) and 61 with aura (MA). Genotypic frequencies: ACE D

Defining a rat blood pressure quantitative trait locus to a <81.8 kb congenic segment: comprehensive sequencing and renal transcriptome analysis

Evidence from multiple linkage and genome-wide association studies suggest that human chromosome 2 (HSA2) contains alleles that influence blood pressure (BP). Homologous to a large segment of HSA2 is rat chromosome 9 (RNO9), to which a BP quantitative trait locus (QTL) was previously mapped. The objective of the current study was to further resolve this BP QTL. Eleven congenic strains with introgressed segments spanning <81.8 kb to <1.33 Mb were developed by introgressing genomic segments of RNO9 from the Dahl salt-resistant (R) rat onto the genome of the Dahl salt-sensitive (S) rat and tested for BP. The congenic strain with the shortest introgressed segment spanning <81.8 kb significantly lowered BP of the hypertensive S rat by 25 mmHg and significantly increased its mean survival by 45 days. In contrast, two other congenic strains had increased BP compared with the S. We focused on the <81.8 kb congenic strain, which represents the shortest genomic segment to which a BP QTL has been mapped to date in any species. Sequencing of this entire region in both S and R rats detected 563 variants. The region did not contain any known or predicted rat protein coding genes. Furthermore, a whole genome renal transcriptome analysis between S and the <81.8 kb S.R congenic strain revealed alterations in several critical genes implicated in renal homeostasis. Taken together, our results provide the basis for future studies to examine the relationship between the candidate variants within the QTL region and the renal differentially expressed genes as potential causal mechanisms for BP regulation