We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula. ...We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming. We reveal sporadic contacts between Iberia and North Africa by ~2500 BCE and, by ~2000 BCE, the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with Steppe ancestry. We show that, in the Iron Age, Steppe ancestry had spread not only into Indo-European-speaking regions but also into non-Indo-European-speaking ones, and we reveal that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia. Additionally, we document how, beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean.
Genetic alterations in adult T‐cell leukemia/lymphoma (ATLL), a T‐cell malignancy associated with HTLV‐1, and their clinical impacts, especially from the perspective of viral strains, are not fully ...elucidated. We employed targeted next‐generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV‐1 tax subgroup‐A (HTLV‐1‐taxA) is notably higher than that in mainland Japan, where most ATLL cases have HTLV‐1‐taxB, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR/NF‐ĸB (eg, PRKCB, PLCG1, and CARD11) and T‐cell trafficking pathways (CCR4 and CCR7), in contrast with North American patients who exhibited a predominance of epigenome‐associated gene mutations. Some mutations, especially GATA3 and RHOA, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV‐1‐taxB, HTLV‐1‐taxA was significantly dominant in Okinawan patients with these mutations (GATA3, 34.1% vs 14.6%, P = .044; RHOA, 24.4% vs 6.3%, P = .032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of PRDM1 (P = .027) in addition to the previously reported PRKCB mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics.
Targeted next‐generation sequencing and single nucleotide polymorphism array were applied to analyze aggressive adult T‐cell leukemia/lymphoma in Okinawa, which were not included in prior genomic studies. Our results showed that HTLV‐1 tax subgroup‐A was associated with high alteration frequencies in GATA3 and RHOA. Clinically, biallelic alterations, not heterozygous deletions or mutations, of PRDM1 were significantly associated with poor prognosis.
Ribosome assembly coming into focus Klinge, Sebastian; Woolford, Jr, John L
Nature reviews. Molecular cell biology,
02/2019, Letnik:
20, Številka:
2
Journal Article
Recenzirano
Odprti dostop
In the past 25 years, genetic and biochemical analyses of ribosome assembly in yeast have identified most of the factors that participate in this complex pathway and have generated models for the ...mechanisms driving the assembly. More recently, the publication of numerous cryo-electron microscopy structures of yeast ribosome assembly intermediates has provided near-atomic resolution snapshots of ribosome precursor particles. Satisfyingly, these structural data support the genetic and biochemical models and provide additional mechanistic insight into ribosome assembly. In this Review, we discuss the mechanisms of assembly of the yeast small ribosomal subunit and large ribosomal subunit in the nucleolus, nucleus and cytoplasm. Particular emphasis is placed on concepts such as the mechanisms of RNA compaction, the functions of molecular switches and molecular mimicry, the irreversibility of assembly checkpoints and the roles of structural and functional proofreading of pre-ribosomal particles.
Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of ...clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10
), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
Biological networks are powerful resources for the discovery of genes and genetic modules that drive disease. Fundamental to network analysis is the concept that genes underlying the same phenotype ...tend to interact; this principle can be used to combine and to amplify signals from individual genes. Recently, numerous bioinformatic techniques have been proposed for genetic analysis using networks, based on random walks, information diffusion and electrical resistance. These approaches have been applied successfully to identify disease genes, genetic modules and drug targets. In fact, all these approaches are variations of a unifying mathematical machinery - network propagation - suggesting that it is a powerful data transformation method of broad utility in genetic research.
•We investigated the inheritance of main flower characteristics via a heterosis analysis and major gene plus polygene genetic analysis.•Transgressive segregation of the main flower characteristics ...was commonly observed in the F1 generation, except for corolla color value.•Inflorescence diameter and inflorescence length were best fit by the A-0 model, indicating that they were controlled by only polygenes.•Number of flowers per inflorescence, beginning of the blooming period, inflorescence number, flower diameter and length were controlled by major genes.
The ornamental characteristics of Plumbago auriculata are mainly reflected in the floral organ. Exploring the genetic inheritance of flower characteristics is important for breeding new varieties. In this study, F1 segregating populations were obtained by using artificial hybridization (direct cross and reciprocal cross) between P. auriculata and its variant P. auriculata f. alba. A heterosis analysis and mixed major gene plus polygene inheritance model were used to investigate the inheritance of eight flower characteristics in the F1 generation: inflorescence length (IL), inflorescence diameter (ID), number of flowers per inflorescence (NFI), beginning of the blooming period (BBP), inflorescence number (IN), flower diameter (FD), flower length (FL) and corolla color value (CCV). In addition to the CCV, the other flower characteristics showed continuous unimodal and skewed distributions, which indicated that these characteristics were quantitative and controlled by polygenes. Although transgressive heterosis was observed only for BBP in both combinations, transgressive segregation was commonly observed, except for CCV in the F1 generation; these findings could facilitate the selection of beneficial individuals for breeding. Genetic analysis revealed that NFI could be described by a B-3 genetic model via two pairs of additive major genes; BBP could be followed by a B-2 genetic model via two pairs of additive-dominance major genes; both FL and FD could be described by a B-6 genetic model via two pairs of major genes that were equally dominant; IN was best fit by the A-1 model, which was controlled by a pair of additive-dominant-epistatic major genes; and IL and ID were best fit by the A-0 model, indicating that both characteristics were controlled by only polygenes. The heritability of the major genes controlling the NFI, BBP, FD, FL and IN traits were 92.58 %, 94.40 %, 63.42 %, 54.23 % and 65.67 %, respectively, indicating that these five characteristics were less affected by the environment. These results can provide some reference for quantitative trait locus (QTL) mapping and molecular marker-assisted breeding of the main flower characteristics in P. auriculata.
In this review, we argue that several key features of maximal oxygen uptake (VO2max) should underpin discussions about the biological and reductionist determinants of its interindividual variability: ...(i) training‐induced increases in VO2max are largely facilitated by expansion of red blood cell volume and an associated improvement in stroke volume, which also adapts independent of changes in red blood cell volume. These general concepts are also informed by cross‐sectional studies in athletes that have very high values for VO2max. Therefore, (ii) variations in VO2max improvements with exercise training are also likely related to variations in these physiological determinants. (iii) All previously untrained individuals will respond to endurance exercise training in terms of improvements in VO2max provided the stimulus exceeds a certain volume and/or intensity. Thus, genetic analysis and/or reductionist studies performed to understand or predict such variations might focus specifically on DNA variants or other molecular phenomena of relevance to these physiological pathways.
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