Structure and chromosomal location of the bovine gene for the heart muscle isoform of cytochrome c oxidase subunit VIII

We have isolated the bovine COX8H gene for the heart/muscle isoform of cytochrome c oxidase (COX) subunit VIII from a library of bovine genomic DNA cloned into lambda EMBL3. Primer extension assays on bovine heart mRNA mapped the 5′ ends of COX8H transcripts to a CA dinucleotide 62-bp upstream from the ATG codon. The gene thus spans 1565-bp and comprises two exons and one large intron of 1227 bp. Exon 1 encodes the 5′ untranslated region, a 24-amino acid presequence, and the first 13 amino acids of the mature COX VIII-H protein. Exon 2 encodes the remainder of the cDNA: amino acids 14 to 46 plus the 66-bp 3′ untranslated region. The exon-intron boundaries matched the consensus splice junction sequences. Two protein polymorphisms were seen: an Ala/Val polymorphism at position-6 in the presequence and the previously noted Lys/Arg polymorphism at residue 7 of the mature protein. A Taq I polymorphism occurs in the intron. The COX8H gene was mapped by bovine x rodent somatic cell hybrid mapping panels to bovine (BTA) Chromosome (Chr) 25 with 100% concordancy. BTA25 is conserved relative to the long arm of human (HSA) Chr 11, which contains COX8, the gene for the single human COX VIII subunit that is homologous to the liver isoform.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47018/1/335_2004_Article_BF00303255.pd

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

TRY plant trait database – enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

El mapa génico bovino: una herramienta para el clonaje posicional comparativo

El mapa del genoma bovino incluye un mapa sinténico, un mapa de ligamiento y al menos uno de hibridación in situ para cada cromosoma. Bastante más de 1000 marcadores han sido localizados en al menos tres mapas de ligamiento publicados. Esos marcadores están siendo empleados ahora a un ritmo acelerado para generar mapas de loci de trascendencia económica (ETL). La cuestión de identificar los genes responsables de los ETL incluidos en el mapa del bovino (y de otras especies ganaderas) es formidable. Una propuesta para abordarla consiste en el clonaje de los candidatos posicionales comparativos, mediante el cual, se obtienen genes candidatos de los mapas del hombre y el ratón, a partir del mapa comparativo bovino. Esto ha puesto de manifiesto que la identificación de la sintenia conservada entre especies, es insuficiente para el clonaje del candidato posicional comparativo, a causa de los reordenamientos del orden de los genes que son abundantes dentro de los grupos de sintenia conservados. A este fin, nuestro laboratorio, y otros, se encuentran ordenando los marcadores para la elaboración de mapas comparativos (loci tipo I) en el mapa bovino. Para ilustrar la orientación y el reordenamiento dentro de regiones de sintenia conservada en bovinos, humanos y ratón, se presentan ejemplos del orden de los genes en los cromosomas bovinos 1, 7 y 19. Los experimentos en marcha, para finalmente aclarar el orden de los genes, incluyen un retrocruzamiento híbrido interespecifico y análisis por radiación de células somáticas híbridas

El mapa génico bovino: una herramienta para el clonaje posicional comparativo

El mapa del genoma bovino incluye un mapa sinténico, un mapa de ligamiento y al menos uno de hibridación in situ para cada cromosoma. Bastante más de 1000 marcadores han sido localizados en al menos tres mapas de ligamiento publicados. Esos marcadores están siendo empleados ahora a un ritmo acelerado para generar mapas de loci de trascendencia económica (ETL). La cuestión de identificar los genes responsables de los ETL incluidos en el mapa del bovino (y de otras especies ganaderas) es formidable. Una propuesta para abordarla consiste en el clonaje de los candidatos posicionales comparativos, mediante el cual, se obtienen genes candidatos de los mapas del hombre y el ratón, a partir del mapa comparativo bovino. Esto ha puesto de manifiesto que la identificación de la sintenia conservada entre especies, es insuficiente para el clonaje del candidato posicional comparativo, a causa de los reordenamientos del orden de los genes que son abundantes dentro de los grupos de sintenia conservados. A este fin, nuestro laboratorio, y otros, se encuentran ordenando los marcadores para la elaboración de mapas comparativos (loci tipo I) en el mapa bovino. Para ilustrar la orientación y el reordenamiento dentro de regiones de sintenia conservada en bovinos, humanos y ratón, se presentan ejemplos del orden de los genes en los cromosomas bovinos 1, 7 y 19. Los experimentos en marcha, para finalmente aclarar el orden de los genes, incluyen un retrocruzamiento híbrido interespecifico y análisis por radiación de células somáticas híbridas

Analysis of sequence variability and protein domain architectures for bovine peptidoglycan recognition protein 1 and Toll-like receptors 2 and 6

AbstractThe mammalian Toll-like receptors (TLRs) recognize invading pathogens, thereafter provoking innate immune responses, whereas peptidoglycan recognition protein 1 (PGLYRP1) is directly microbicidal. The primary objective of this study was to characterize single-nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (indels) within bovine TLR2, TLR6, and PGLYRP1, thereby facilitating future TLR signaling, association, and PGLYRP1 microbicidal assays relevant to bovine innate immunity. Comparative sequence analysis for 10 bovine breeds revealed 83 polymorphisms (82 SNPs, 1 indel), with 15 nonsynonymous SNPs located within predicted functional domains. Of the 83 polymorphisms detected, 72 (87%) are reported here for the first time. Several predicted amino acid replacements encoded by bovine TLR2 and TLR6, but not PGLYRP1, resulted in the confident prediction of protein domain alterations. Prediction and comparison of protein domain architectures for TLR2 and TLR6 revealed six regions of leucine-rich-repeat patterning that was conserved among multiple species. Collectively, differences in the patterns and frequencies of polymorphism were noted between bovine TLRs that predominantly recognize viral ligands (TLRs 3, 7, 8, 9) and those that recognize microbial and/or unknown ligands (TLRs 1, 2, 5, 6, 10)