A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations

Superolateral Hoffa fat pad edema in adolescent competitive alpine skiers: temporal evolution over 4 years and risk factors

Abstract Objectives To longitudinally assess and correlate the prevalence of superolateral Hoffa fat pad (SHFP) edema with changes in features of the knee extensor mechanism in adolescent competitive alpine skiers over 48 months. Methods Competitive alpine skiers were prospectively enrolled in 2018 and underwent bilateral knee MRI at baseline and after 48 months. MRI was assessed for the prevalence of SHFP edema. Features of the knee extensor mechanism were assessed by measuring the trochlear sulcus angle and depth, lateral and medial trochlear inclination, trochlear angle, patella tilt, Insall‒Salvati ratio (ISR), and patellar ligament to lateral trochlear facet (PL-T) distance. Separate logistic regression models were used to calculate the odds ratios between each measurement and the presence of SHFP edema at both time points. Results Sixty-three athletes were included in the study (mean age 15.3 ± 1.3 years, 25 women). At baseline, 23 knees had SHFP edema, increasing to 34 knees at the 48-month follow-up. At baseline, knees with measurements in the highest quartile for ISR and lowest quartile for trochlear depth and PL-T were 9.3, 5.1, and 7.7 times more likely to show SHFP edema, respectively. At follow-up, these correlations were confirmed and additionally, knees with measurements in the highest quartile for trochlear sulcus angle and the lowest quartile for lateral trochlear inclination were 4.1 and 3.4 times more likely to show SHFP edema. Conclusion An increased prevalence of SHFP edema in competitive alpine skiers during adolescence was associated with persistent high-riding patella, reduced patellar ligament to trochlear distance, and flattened lateral trochlear facet. Critical relevance statement In clinical routine, assessment of the mechanical properties of the knee extensor mechanism, together with anatomical developments during adolescence, may improve the understanding and management of patellofemoral instability. Key points • Superolateral Hoffa fat pad (SHFP) edema is a frequent cause of anterolateral knee pain but the role of predisposing factors is still debated. • A higher prevalence of SHFP edema was associated with high-riding patella, reduced patellar ligament to trochlear distance, and flattened lateral trochlear facet. • Understanding of the mechanical interaction and the anatomical development of the knee during adolescence provides further insight into the development of SHFP edema. Graphical Abstrac

Invest in the future: “Hands-on Radiology” summer school

Key points 1. The three-day student program enhanced the visibility of radiology as a specialization. 2. Interest in and knowledge of radiology was increased among participants. 3. Participants’ motivation to consider specialization in radiology increased. 4. Participants favored onsite teaching and teaching by residents instead of consultants. 5. Networking is a major factor during such courses among participants

Mapping copy number variation by population-scale genome sequencing.

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies

Mapping copy number variation by population-scale genome sequencing

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies. © 2011 Macmillan Publishers Limited. All rights reserved.Link_to_subscribed_fulltex

An integrated map of structural variation in 2,504 human genomes

Summary Structural variants (SVs) are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight SV classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype-blocks in 26 human populations. Analyzing this set, we identify numerous gene-intersecting SVs exhibiting population stratification and describe naturally occurring homozygous gene knockouts suggesting the dispensability of a variety of human genes. We demonstrate that SVs are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of SV complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex SVs with multiple breakpoints likely formed through individual mutational events. Our catalog will enhance future studies into SV demography, functional impact and disease association

Mapping copy number variation by population-scale genome sequencing.

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies