Mobile DNA elements in primate and human evolution

Roughly 50% of the primate genome consists of mobile, repetitive DNA sequences such as Alu and LINE1 elements. The causes and evolutionary consequences of mobile element insertion, which have received considerable attention during the past decade, are reviewed in this article. Because of their unique mutational mechanisms, these elements are highly useful for answering phylogenetic questions. We demonstrate how they have been used to help resolve a number of questions in primate phylogeny, including the human-chimpanzee- gorilla trichotomy and New World primate phylogeny. Alu and LINE1 element insertion polymorphisms have also been analyzed in human populations to test hypotheses about human evolution and population affinities and to address forensic issues. Finally, these elements have had impacts on the genome itself. We review how they have influenced fundamental ongoing processes like nonhomologous recombination, genomic deletion, and X chromosome inactivation. © 2007 Wiley-Liss, Inc

Mobile element scanning (ME-Scan) by targeted high-throughput sequencing

<p>Abstract</p> <p>Background</p> <p>Mobile elements (MEs) are diverse, common and dynamic inhabitants of nearly all genomes. ME transposition generates a steady stream of polymorphic genetic markers, deleterious and adaptive mutations, and substrates for further genomic rearrangements. Research on the impacts, population dynamics, and evolution of MEs is constrained by the difficulty of ascertaining rare polymorphic ME insertions that occur against a large background of pre-existing fixed elements and then genotyping them in many individuals.</p> <p>Results</p> <p>Here we present a novel method for identifying nearly all insertions of a ME subfamily in the whole genomes of multiple individuals and simultaneously genotyping (for presence or absence) those insertions that are variable in the population. We use ME-specific primers to construct DNA libraries that contain the junctions of all ME insertions of the subfamily, with their flanking genomic sequences, from many individuals. Individual-specific "index" sequences are designed into the oligonucleotide adapters used to construct the individual libraries. These libraries are then pooled and sequenced using a ME-specific sequencing primer. Mobile element insertion loci of the target subfamily are uniquely identified by their junction sequence, and all insertion junctions are linked to their individual libraries by the corresponding index sequence. To test this method's feasibility, we apply it to the human <it>AluYb8 </it>and <it>AluYb9 </it>subfamilies. In four individuals, we identified a total of 2,758 <it>AluYb8 </it>and <it>AluYb9 </it>insertions, including nearly all those that are present in the reference genome, as well as 487 that are not. Index counts show the sequenced products from each sample reflect the intended proportions to within 1%. At a sequencing depth of 355,000 paired reads per sample, the sensitivity and specificity of ME-Scan are both approximately 95%.</p> <p>Conclusions</p> <p>Mobile Element Scanning (ME-Scan) is an efficient method for quickly genotyping mobile element insertions with very high sensitivity and specificity. In light of recent improvements to high-throughput sequencing technology, it should be possible to employ ME-Scan to genotype insertions of almost any mobile element family in many individuals from any species.</p

Mobile element scanning (ME-Scan) identifies thousands of novel Alu insertions in diverse human populations

Alu retrotransposons are the most numerous and active mobile elements in humans, causing genetic disease and creating genomic diversity. Mobile element scanning (ME-Scan) enables comprehensive and affordable identification of mobile element insertions (MEI) using targeted high-throughput sequencing of multiplexed MEI junction libraries. In a single experiment, ME-Scan identifies nearly all AluYb8 and AluYb9 elements, with high sensitivity for both rare and common insertions, in 169 individuals of diverse ancestry. ME-Scan detects heterozygous insertions in single individuals with 91% sensitivity. Insertion presence or absence states determined by ME-Scan are 95% concordant with those determined by locus-specific PCR assays. By sampling diverse populations from Africa, South Asia, and Europe, we are able to identify 5799 Alu insertions, including 2524 novel ones, some of which occur in exons. Sub-Saharan populations and a Pygmy group in particular carry numerous intermediate-frequency Alu insertions that are absent in non-African groups. There is a significant dearth of exon-interrupting insertions among common Alu polymorphisms, but the density of singleton Alu insertions is constant across exonic and nonexonic regions. In one case, a validated novel singleton Alu interrupts a proteincoding exon of FAM187B. This implies that exonic Alu insertions are generally deleterious and thus eliminated by natural selection, but not so quickly that they cannot be observed as extremely rare variants. © 2013, Published by Cold Spring Harbor Laboratory Press

Modeling the Amplification Dynamics of Human Alu Retrotransposons

Retrotransposons have had a considerable impact on the overall architecture of the human genome. Currently, there are three lineages of retrotransposons (Alu, L1, and SVA) that are believed to be actively replicating in humans. While estimates of their copy number, sequence diversity, and levels of insertion polymorphism can readily be obtained from existing genomic sequence data and population sampling, a detailed understanding of the temporal pattern of retrotransposon amplification remains elusive. Here we pose the question of whether, using genomic sequence and population frequency data from extant taxa, one can adequately reconstruct historical amplification patterns. To this end, we developed a computer simulation that incorporates several known aspects of primate Alu retrotransposon biology and accommodates sampling effects resulting from the methods by which mobile elements are typically discovered and characterized. By modeling a number of amplification scenarios and comparing simulation-generated expectations to empirical data gathered from existing Alu subfamilies, we were able to statistically reject a number of amplification scenarios for individual subfamilies, including that of a rapid expansion or explosion of Alu amplification at the time of human–chimpanzee divergence

Alu repeats increase local recombination rates

BACKGROUND: Recombination rates vary widely across the human genome, but little of that variation is correlated with known DNA sequence features. The genome contains more than one million Alu mobile element insertions, and these insertions have been implicated in non-homologous recombination, modulation of DNA methylation, and transcriptional regulation. If individual Alu insertions have even modest effects on local recombination rates, they could collectively have a significant impact on the pattern of linkage disequilibrium in the human genome and on the evolution of the Alu family itself. RESULTS: We carried out sequencing, SNP identification, and SNP genotyping around 19 AluY insertion loci in 347 individuals sampled from diverse populations, then used the SNP genotypes to estimate local recombination rates around the AluY loci. The loci and SNPs were chosen so as to minimize other factors (such as SNP ascertainment bias and SNP density) that could influence recombination rate estimates. We detected a significant increase in recombination rate within ~2 kb of the AluY insertions in our African population sample. To test this observation against a larger set of AluY insertions, we applied our locus- and SNP-selection design and analyses to the HapMap Phase II data. In that data set, we observed a significantly increased recombination rate near AluY insertions in both the CEU and YRI populations. CONCLUSION: We show that the presence of a fixed AluY insertion is significantly predictive of an elevated local recombination rate within 2 kb of the insertion, independent of other known predictors. The magnitude of this effect, approximately a 6% increase, is comparable to the effects of some recombinogenic DNA sequence motifs identified via their association with recombination hot spots

Особенности терапии атипичного герпеса и ассоциированного с ним рецидивирующего вульвовагинального кандидоза

КАНДИДОЗ ВУЛЬВОВАГИНАЛЬНЫЙ /ЛЕК ТЕРВЛАГАЛИЩА БОЛЕЗНИ /ЛЕК ТЕРВУЛЬВЫ БОЛЕЗНИ /ЛЕК ТЕРЖЕНСКИЕ БОЛЕЗНИ /ЛЕК ТЕРПРОТИВОГРИБКОВЫЕ СРЕДСТВАПРОТИВОВИРУСНЫЕ СРЕДСТВАГЕРПЕСВИРУСНЫЕ ИНФЕКЦИИРЕЦИДИВГЕРПЕСВИРУС 1 ЧЕЛОВЕКАГЕРПЕСВИРУС 2 ЧЕЛОВЕК

Triple-gated motion and blood pool clearance corrections improve reproducibility of coronary 18F-NaF PET

PurposeTo improve the test-retest reproducibility of coronary plaque 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) uptake measurements.MethodsWe recruited 20 patients with coronary artery disease who underwent repeated hybrid PET/CT angiography (CTA) imaging within 3&nbsp;weeks. All patients had 30-min PET acquisition and CTA during a single imaging session. Five PET image-sets with progressive motion correction were reconstructed: (i) a static dataset (no-MC), (ii) end-diastolic PET (standard), (iii) cardiac motion corrected (MC), (iv) combined cardiac and gross patient motion corrected (2 × MC) and, (v) cardiorespiratory and gross patient motion corrected (3 × MC). In addition to motion correction, all datasets were corrected for variations in the background activities which are introduced by variations in the injection-to-scan delays (background blood pool clearance correction, BC). Test-retest reproducibility of PET target-to-background ratio (TBR) was assessed by Bland-Altman analysis and coefficient of reproducibility.ResultsA total of 47 unique coronary lesions were identified on CTA. Motion correction in combination with BC improved the PET TBR test-retest reproducibility for all lesions (coefficient of reproducibility: standard = 0.437, no-MC = 0.345 (27% improvement), standard&nbsp;+&nbsp;BC = 0.365 (20% improvement), no-MC + BC = 0.341 (27% improvement), MC + BC = 0.288 (52% improvement), 2 × MC + BC = 0.278 (57% improvement) and 3 × C + BC = 0.254 (72% improvement), all p &lt; 0.001). Importantly, in a sub-analysis of 18F-NaF-avid lesions with gross patient motion &gt;&nbsp;10&nbsp;mm following corrections, reproducibility was improved by 133% (coefficient of reproducibility: standard = 0.745, 3 × MC = 0.320).ConclusionJoint corrections for cardiac, respiratory, and gross patient motion in combination with background blood pool corrections markedly improve test-retest reproducibility of coronary 18F-NaF PET

Ancestry of the Iban Is Predominantly Southeast Asian: Genetic Evidence from Autosomal, Mitochondrial, and Y Chromosomes

Humans reached present-day Island Southeast Asia (ISEA) in one of the first major human migrations out of Africa. Population movements in the millennia following this initial settlement are thought to have greatly influenced the genetic makeup of current inhabitants, yet the extent attributed to different events is not clear. Recent studies suggest that south-to-north gene flow largely influenced present-day patterns of genetic variation in Southeast Asian populations and that late Pleistocene and early Holocene migrations from Southeast Asia are responsible for a substantial proportion of ISEA ancestry. Archaeological and linguistic evidence suggests that the ancestors of present-day inhabitants came mainly from north-to-south migrations from Taiwan and throughout ISEA approximately 4,000 years ago. We report a large-scale genetic analysis of human variation in the Iban population from the Malaysian state of Sarawak in northwestern Borneo, located in the center of ISEA. Genome-wide single-nucleotide polymorphism (SNP) markers analyzed here suggest that the Iban exhibit greatest genetic similarity to Indonesian and mainland Southeast Asian populations. The most common non-recombining Y (NRY) and mitochondrial (mt) DNA haplogroups present in the Iban are associated with populations of Southeast Asia. We conclude that migrations from Southeast Asia made a large contribution to Iban ancestry, although evidence of potential gene flow from Taiwan is also seen in uniparentally inherited marker data

H I - MaNGA : H I follow-up for the MaNGA survey

We present the H I-MaNGA programme of H I follow-up for the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. MaNGA, which is part of the Fourth phase of the Sloan Digital Sky Surveys, is in the process of obtaining integral field unit spectroscopy for a sample of ∼10 000 nearby galaxies. We give an overview of the H I 21cm radio follow-up observing plans and progress and present data for the first 331 galaxies observed in the 2016 observing season at the Robert C. Bryd Green Bank Telescope. We also provide a cross-match of the current MaNGA(DR15) sample with publicly available H I data from the Arecibo Legacy Fast Arecibo L-band Feed Array survey. The addition of H I data to the MaNGA data set will strengthen the survey's ability to address several of its key science goals that relate to the gas content of galaxies, while also increasing the legacy of this survey for all extragalactic science.Publisher PDFPeer reviewe