scholarly journals Non-crossover gene conversions show strong GC bias and unexpected clustering in humans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Amy L Williams ◽  
Giulio Genovese ◽  
Thomas Dyer ◽  
Nicolas Altemose ◽  
Katherine Truax ◽  
...  
Keyword(s):  
Sequence Data ◽  
Snp Array ◽  
Strand Break ◽  
Genome Wide ◽  
Tremendous Progress ◽  
Close Proximity ◽  
Order Of Magnitude ◽  
Gc Bias ◽  
A Site ◽  
Sperm Typing

Although the past decade has seen tremendous progress in our understanding of fine-scale recombination, little is known about non-crossover (NCO) gene conversion. We report the first genome-wide study of NCO events in humans. Using SNP array data from 98 meioses, we identified 103 sites affected by NCO, of which 50/52 were confirmed in sequence data. Overlap with double strand break (DSB) hotspots indicates that most of the events are likely of meiotic origin. We estimate that a site is involved in a NCO at a rate of 5.9 × 10−6/bp/generation, consistent with sperm-typing studies, and infer that tract lengths span at least an order of magnitude. Observed NCO events show strong allelic bias at heterozygous AT/GC SNPs, with 68% (58–78%) transmitting GC alleles (p = 5 × 10−4). Strikingly, in 4 of 15 regions with resequencing data, multiple disjoint NCO tracts cluster in close proximity (∼20–30 kb), a phenomenon not previously seen in mammals.

scholarly journals Non-crossover gene conversions show strong GC bias and unexpected clustering in humans

2014 ◽  
Author(s):  
Amy L. Williams ◽  
Giulio Geneovese ◽  
Thomas Dyer ◽  
Nicolas Altemose ◽  
Katherine Truax ◽  
...  
Keyword(s):  
Sequence Data ◽  
Snp Array ◽  
Strand Break ◽  
Genome Wide ◽  
Tremendous Progress ◽  
Close Proximity ◽  
Order Of Magnitude ◽  
Gc Bias ◽  
A Site ◽  
Sperm Typing

Although the past decade has seen tremendous progress in our understanding of fine-scale recombination, little is known about non-crossover (NCO) gene conversion. We report the first genome-wide study of NCO events in humans. Using SNP array data from 98 meioses, we identified 103 sites affected by NCO, of which 50/52 were confirmed in sequence data. Overlap with double strand break (DSB) hotspots indicates that the events are likely of meiotic origin. We estimate that a site is involved in a NCO at a rate of 5.7×10-6/bp/generation, consistent with sperm-typing studies, and infer that tract lengths span at least an order of magnitude. Observed NCO events show strong allelic bias at heterozygous AT/GC SNPs, with 68% (58?78%) transmitting GC alleles (P=5×10-4). Strikingly, in 4 of 15 regions for which there are also resequencing data, multiple disjoint NCO tracts cluster in close proximity (~20?30 kb), a phenomenon not previously seen in mammals.

Genome-wide association study on chicken carcass traits using sequence data imputed from SNP array

2018 ◽  
Vol 59 (3) ◽  
pp. 335-344 ◽  
Author(s):  
Shuwen Huang ◽  
Yingting He ◽  
Shaopan Ye ◽  
Jiaying Wang ◽  
Xiaolong Yuan ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Sequence Data ◽  
Carcass Traits ◽  
Snp Array ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Chicken Carcass

scholarly journals Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Nature ◽  
2021 ◽  
Vol 590 (7845) ◽  
pp. 290-299 ◽  
Author(s):  
Daniel Taliun ◽  
◽  
Daniel N. Harris ◽  
Michael D. Kessler ◽  
Jedidiah Carlson ◽  
...  
Keyword(s):  
Rare Variants ◽  
Sequence Data ◽  
Association Studies ◽  
Genotype Imputation ◽  
Genome Wide Association Studies ◽  
Phenotypic Data ◽  
Treatment And Prevention ◽  
Genome Wide ◽  
Diverse Backgrounds ◽  
Unmapped Reads

AbstractThe Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.

scholarly journals Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Helena R. R. Wells ◽  
Fatin N. Zainul Abidin ◽  
Maxim B. Freidin ◽  
Frances M. K. Williams ◽  
Sally J. Dawson
Keyword(s):  
Association Study ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Uk Biobank ◽  
Significance Threshold ◽  
Genome Wide ◽  
Final Sample ◽  
Close Proximity ◽  
Repressor Complex

AbstractTinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case–control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E−08), rs4900545 (p = 1.8E−08) and 14:103042287_CT_C (p = 3.50E−08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E−06.

scholarly journals Genome diversity in Ukraine

GigaScience ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Taras K Oleksyk ◽  
Walter W Wolfsberger ◽  
Alexandra M Weber ◽  
Khrystyna Shchubelka ◽  
Olga T Oleksyk ◽  
...  
Keyword(s):  
Sequence Data ◽  
Copy Number Variations ◽  
Genomic Variation ◽  
High Coverage ◽  
Genome Data ◽  
New Information ◽  
Genome Wide ◽  
Public Data ◽  
Genome Wide Data ◽  
Multiple Samples

Abstract Background The main goal of this collaborative effort is to provide genome-wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for public data release. BGISEQ-500 sequence data and genotypes by an Illumina GWAS chip were cross-validated on multiple samples and additionally referenced to 1 sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. Results The genome data have been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, copy number variations, single-nucletide polymorphisms, and microsatellites. To our knowledge, this study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for medical research in a large understudied population. Conclusions Our results indicate that the genetic diversity of the Ukrainian population is uniquely shaped by evolutionary and demographic forces and cannot be ignored in future genetic and biomedical studies. These data will contribute a wealth of new information bringing forth a wealth of novel, endemic and medically related alleles.

scholarly journals RMR-Related MAP2K6 Gene Variation on the Risk of Overweight/Obesity in Children: A 3-Year Panel Study

2021 ◽  
Vol 11 (2) ◽  
pp. 91
Author(s):  
Myoungsook Lee ◽  
Yunkyoung Lee ◽  
Inhae Kang ◽  
Jieun Shin ◽  
Sungbin R. Sorn
Keyword(s):  
Dietary Intake ◽  
Resting Metabolic Rate ◽  
Panel Study ◽  
Snp Array ◽  
Fat Intake ◽  
Nucleotide Polymorphisms ◽  
Korean Children ◽  
Gene Variation ◽  
Genome Wide ◽  
Prevalence Of Obesity

From a pilot GWAS, seven MAP2K6 (MEK6) SNPs were significantly associated with resting metabolic rate (RMR) in obese children aged 8–9 years. The aim of this study was to investigate how RMR-linked MEK6 variation affected obesity in Korean children. With the follow-up students (77.9%) in the 3-year panel study, the changes of the variables associated with obesity (such as anthropometrics, blood biochemistry, and dietary intake) were collected. After the MEK6 SNPs were screened by Affymetrix Genome-Wide Human SNP array 6.0, the genotyping of the seven MEK6 SNPs was performed via SNaPshot assay. As the prevalence of obesity (≥85th percentile) increased from 19.4% to 25.5%, the rates of change of the variables RMR, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), and dietary intake (energy and carbohydrate intakes) increased. The rate of overweight/obesity was higher in all mutant alleles of the seven MEK6 SNPs than it was in the matched children without mutant alleles. However, over the 3-year study period, RMRs were only significantly increased by the mutants of two single nucleotide polymorphisms (SNPs), rs996229 and rs756942, mainly related to male overweight/obesity as both WC and SBP levels increased. In the mutants of two of the SNPs, the odds ratio of overweight/obesity risk was six times higher in the highest tercile of fat intake and SBP than those of the lowest tercile. For personalized medicine to prevent pediatric obesity, SBP, WC, and dietary fat intake should be observed, particularly if boys have mutants of MEK6 SNPs, rs9916229, or rs756942.

scholarly journals Genome-Wide Analyses Identifies Known and New Markers Responsible of Chicken Plumage Color

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 493
Author(s):  
Salvatore Mastrangelo ◽  
Filippo Cendron ◽  
Gianluca Sottile ◽  
Giovanni Niero ◽  
Baldassare Portolano ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Snp Array ◽  
Fixation Index ◽  
Phenotypic Traits ◽  
Plumage Color ◽  
Phenotypic Marker ◽  
Genome Wide ◽  
A Genome ◽  
The Difference ◽  
Genomic Regions

Through the development of the high-throughput genotyping arrays, molecular markers and genes related to phenotypic traits have been identified in livestock species. In poultry, plumage color is an important qualitative trait that can be used as phenotypic marker for breed identification. In order to assess sources of genetic variation related to the Polverara chicken breed plumage colour (black vs. white), we carried out a genome-wide association study (GWAS) and a genome-wide fixation index (FST) scan to uncover the genomic regions involved. A total of 37 animals (17 white and 20 black) were genotyped with the Affymetrix 600 K Chicken single nucleotide polymorphism (SNP) Array. The combination of results from GWAS and FST revealed a total of 40 significant markers distributed on GGA 01, 03, 08, 12 and 21, and located within or near known genes. In addition to the well-known TYR, other candidate genes have been identified in this study, such as GRM5, RAB38 and NOTCH2. All these genes could explain the difference between the two Polverara breeds. Therefore, this study provides the basis for further investigation of the genetic mechanisms involved in plumage color in chicken.

scholarly journals Development and Evaluation of a Genome-Wide 6K SNP Array for Diploid Sweet Cherry and Tetraploid Sour Cherry

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e48305 ◽  
Author(s):  
Cameron Peace ◽  
Nahla Bassil ◽  
Dorrie Main ◽  
Stephen Ficklin ◽  
Umesh R. Rosyara ◽  
...  
Keyword(s):  
Sweet Cherry ◽  
Snp Array ◽  
Sour Cherry ◽  
Genome Wide ◽  
A Genome

scholarly journals Sites of Acetylation on Newly Synthesized Histone H4 Are Required for Chromatin Assembly and DNA Damage Response Signaling

2013 ◽  
Vol 33 (16) ◽  
pp. 3286-3298 ◽  
Author(s):  
Zhongqi Ge ◽  
Devi Nair ◽  
Xiaoyan Guan ◽  
Neha Rastogi ◽  
Michael A. Freitas ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Histone H3 ◽  
Model Organism ◽  
Strand Break ◽  
Chromatin Assembly ◽  
Histone H4 ◽  
Histone H4 Acetylation ◽  
Damage Response ◽  
A Site

The best-characterized acetylation of newly synthesized histone H4 is the diacetylation of the NH2-terminal tail on lysines 5 and 12. Despite its evolutionary conservation, this pattern of modification has not been shown to be essential for either viability or chromatin assembly in any model organism. We demonstrate that mutations in histone H4 lysines 5 and 12 in yeast confer hypersensitivity to replication stress and DNA-damaging agents when combined with mutations in histone H4 lysine 91, which has also been found to be a site of acetylation on soluble histone H4. In addition, these mutations confer a dramatic decrease in cell viability when combined with mutations in histone H3 lysine 56. We also show that mutation of the sites of acetylation on newly synthesized histone H4 results in defects in the reassembly of chromatin structure that accompanies the repair of HO-mediated double-strand breaks. This defect is not due to a decrease in the level of histone H3 lysine 56 acetylation. Intriguingly, mutations that alter the sites of newly synthesized histone H4 acetylation display a marked decrease in levels of phosphorylated H2A (γ-H2AX) in chromatin surrounding the double-strand break. These results indicate that the sites of acetylation on newly synthesized histones H3 and H4 can function in nonoverlapping ways that are required for chromatin assembly, viability, and DNA damage response signaling.

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