scholarly journals Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability

2019 ◽  
Author(s):  
Richard J. Wang ◽  
Gregg W.C. Thomas ◽  
Muthuswamy Raveendran ◽  
R. Alan Harris ◽  
Harshavardhan Doddapaneni ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Neurodevelopmental Disorders ◽  
Complex Disease ◽  
De Novo ◽  
Sequence Data ◽  
Mutation Accumulation ◽  
Paternal Age ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Increased Risk

AbstractMutation is the ultimate source of all genetic novelty and the cause of heritable genetic disorders. Mutational burden has been linked to complex disease, including neurodevelopmental disorders such as schizophrenia and autism. The rate of mutation is a fundamental genomic parameter and direct estimates of this parameter have been enabled by accurate comparisons of whole-genome sequences between parents and offspring. Studies in humans have revealed that the paternal age at conception explains most of the variation in mutation rate: each additional year of paternal age in humans leads to approximately 1.5 additional mutations inherited by the child. Here, we present an estimate of the de novo mutation rate in the rhesus macaque (Macaca mulatta) using whole-genome sequence data from 32 individuals in four large pedigrees. We estimated an average mutation rate of 0.58 × 10-8 per base pair per generation (at an average parental age of 7.5 years), much lower than found in direct estimates from great apes (including human, chimpanzee, and gorilla). As in humans, older macaque fathers transmit more mutations to their offspring, approximately 1.5 extra mutations per year in our probands. Mutations at CpG sites accounted for 24% of all observed point mutations. We found that the rate of mutation accumulation after puberty is similar between macaques and humans, but that a smaller number of mutations accumulate before puberty in macaques. We additionally investigated the role of paternal age on offspring sociability, a proxy for normal neurodevelopment. In 203 male macaques studied in large social groups, we found no relationship between paternal age and multiple measures of social function. Our findings are consistent with the hypothesis that the increased risk of neurodevelopmental disorders with paternal age in primates is not primarily due to de novo mutations.

scholarly journals De Novo Gene Evolution of Antifreeze Glycoproteins in Codfishes Revealed by Whole Genome Sequence Data

2017 ◽  
Vol 35 (3) ◽  
pp. 593-606 ◽  
Author(s):  
Helle Tessand Baalsrud ◽  
Ole Kristian Tørresen ◽  
Monica Hongrø Solbakken ◽  
Walter Salzburger ◽  
Reinhold Hanel ◽  
...  
Keyword(s):  
Genome Sequence ◽  
De Novo ◽  
Gene Evolution ◽  
Sequence Data ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Antifreeze Glycoproteins ◽  
Genome Sequence Data ◽  
De Novo Gene

scholarly journals Comprehensive analysis of GBA using a novel algorithm for Illumina whole-genome sequence data or targeted Nanopore sequencing

2021 ◽  
Author(s):  
Marco Toffoli ◽  
Xiao Chen ◽  
Fritz J Sedlazeck ◽  
Chiao-Yin Lee ◽  
Stephen Mullin ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Sequence Data ◽  
Whole Genome Sequence ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Short Read ◽  
Increased Risk ◽  
Long Read

GBA variants cause the autosomal recessive Gaucher disease, and carriers are at increased risk of Parkinson disease (PD) and Lewy body dementia (LBD). The presence of a highly homologous nearby pseudogene (GBAP1) predisposes to a range of structural variants arising from either gene conversion or reciprocal recombination, the latter resulting in copy number gains or losses, complicating genetic testing and analysis. To date, short-read sequencing has not been able to fully resolve these or other variants in the key homology region, and targeted long-read sequencing has not previously resolved reciprocal recombinants. We present and validate two independent methods to resolve recombinant alleles and other variants in GBA: Gauchian, a novel bioinformatics tool for short-read, whole-genome sequencing data analysis, and Oxford Nanopore long-read sequencing after enrichment with appropriate PCR. The methods were concordant for 42 samples including 30 with a range of recombinants and GBAP1-related mutations, and Gauchian outperforms the GATK Best Practices pipeline. Applying Gauchian to Illumina sequencing of over 10,000 individuals from publicly available cohorts shows that copy number variants (CNVs) spanning GBAP1 are relatively common in Africans. CNV frequencies in PD and LBD are similar to controls, but gains may coexist with other mutations in patients, and a modifying effect cannot be excluded. Gauchian detects a higher frequency of GBA variants in LBD than PD, especially severe ones. These findings highlight the importance of accurate GBA mutation detection in these patients, which is possible by either Gauchian analysis of short-read whole genome sequencing, or targeted long-read sequencing.

TIGER: inferring DNA replication timing from whole-genome sequence data

2021 ◽  
Author(s):  
Amnon Koren ◽  
Dashiell J Massey ◽  
Alexa N Bracci
Keyword(s):  
Dna Replication ◽  
Genome Sequence ◽  
Genomic Dna ◽  
Sequence Data ◽  
Replication Timing ◽  
Whole Genome Sequence ◽  
Supplementary Information ◽  
Whole Genome ◽  
Genome Sequence Data ◽  
Dna Replication Timing

Abstract Motivation Genomic DNA replicates according to a reproducible spatiotemporal program, with some loci replicating early in S phase while others replicate late. Despite being a central cellular process, DNA replication timing studies have been limited in scale due to technical challenges. Results We present TIGER (Timing Inferred from Genome Replication), a computational approach for extracting DNA replication timing information from whole genome sequence data obtained from proliferating cell samples. The presence of replicating cells in a biological specimen leads to non-uniform representation of genomic DNA that depends on the timing of replication of different genomic loci. Replication dynamics can hence be observed in genome sequence data by analyzing DNA copy number along chromosomes while accounting for other sources of sequence coverage variation. TIGER is applicable to any species with a contiguous genome assembly and rivals the quality of experimental measurements of DNA replication timing. It provides a straightforward approach for measuring replication timing and can readily be applied at scale. Availability and Implementation TIGER is available at https://github.com/TheKorenLab/TIGER. Supplementary information Supplementary data are available at Bioinformatics online

scholarly journals Whole genome sequence data of Mycobacterium tuberculosis XDR strain, isolated from patient in Kazakhstan

Data in Brief ◽  
2020 ◽  
Vol 33 ◽  
pp. 106416
Author(s):  
Asset Daniyarov ◽  
Askhat Molkenov ◽  
Saule Rakhimova ◽  
Ainur Akhmetova ◽  
Zhannur Nurkina ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Genome Sequence ◽  
Sequence Data ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Genome Sequence Data

scholarly journals Elucidating the genetic basis of an oligogenic birth defect using whole genome sequence data in a non-model organism, Bubalus bubalis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lynsey K. Whitacre ◽  
Jesse L. Hoff ◽  
Robert D. Schnabel ◽  
Sara Albarella ◽  
Francesca Ciotola ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Birth Defect ◽  
Genetic Basis ◽  
Sequence Data ◽  
Model Organism ◽  
Bubalus Bubalis ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Genome Sequence Data

scholarly journals Whole genome characterization of strains belonging to the Ralstonia solanacearum species complex and in silico analysis of TaqMan assays for detection in this heterogenous species complex

2021 ◽  
Author(s):  
Viola Kurm ◽  
Ilse Houwers ◽  
Claudia E. Coipan ◽  
Peter Bonants ◽  
Cees Waalwijk ◽  
...  
Keyword(s):  
Ralstonia Solanacearum ◽  
In Silico ◽  
Species Complex ◽  
Sequence Data ◽  
In Silico Analysis ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Genome Sequences ◽  
Pcr Assays

AbstractIdentification and classification of members of the Ralstonia solanacearum species complex (RSSC) is challenging due to the heterogeneity of this complex. Whole genome sequence data of 225 strains were used to classify strains based on average nucleotide identity (ANI) and multilocus sequence analysis (MLSA). Based on the ANI score (>95%), 191 out of 192(99.5%) RSSC strains could be grouped into the three species R. solanacearum, R. pseudosolanacearum, and R. syzygii, and into the four phylotypes within the RSSC (I,II, III, and IV). R. solanacearum phylotype II could be split in two groups (IIA and IIB), from which IIB clustered in three subgroups (IIBa, IIBb and IIBc). This division by ANI was in accordance with MLSA. The IIB subgroups found by ANI and MLSA also differed in the number of SNPs in the primer and probe sites of various assays. An in-silico analysis of eight TaqMan and 11 conventional PCR assays was performed using the whole genome sequences. Based on this analysis several cases of potential false positives or false negatives can be expected upon the use of these assays for their intended target organisms. Two TaqMan assays and two PCR assays targeting the 16S rDNA sequence should be able to detect all phylotypes of the RSSC. We conclude that the increasing availability of whole genome sequences is not only useful for classification of strains, but also shows potential for selection and evaluation of clade specific nucleic acid-based amplification methods within the RSSC.

46 Footprints of Selection in Angus and Hanwoo Beef Cattle Using Imputed Whole Genome Sequence Data

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 25-25
Author(s):  
Muhammad Yasir Nawaz ◽  
Rodrigo Pelicioni Savegnago ◽  
Cedric Gondro
Keyword(s):  
Beef Cattle ◽  
Genome Sequence ◽  
Sequence Data ◽  
Whole Genome Sequence ◽  
Fixation Index ◽  
Whole Genome ◽  
Extended Haplotype Homozygosity ◽  
Extended Haplotype ◽  
Genome Sequence Data ◽  
Genomic Regions

Abstract In this study, we detected genome wide footprints of selection in Hanwoo and Angus beef cattle using different allele frequency and haplotype-based methods based on imputed whole genome sequence data. Our dataset included 13,202 Angus and 10,437 Hanwoo animals with 10,057,633 and 13,241,550 imputed SNPs, respectively. A subset of data with 6,873,624 common SNPs between the two populations was used to estimate signatures of selection parameters, both within (runs of homozygosity and extended haplotype homozygosity) and between (allele fixation index, extended haplotype homozygosity) the breeds in order to infer evidence of selection. We observed that correlations between various measures of selection ranged between 0.01 to 0.42. Assuming these parameters were complementary to each other, we combined them into a composite selection signal to identify regions under selection in both beef breeds. The composite signal was based on the average of fractional ranks of individual selection measures for every SNP. We identified some selection signatures that were common between the breeds while others were independent. We also observed that more genomic regions were selected in Angus as compared to Hanwoo. Candidate genes within significant genomic regions may help explain mechanisms of adaptation, domestication history and loci for important traits in Angus and Hanwoo cattle. In the future, we will use the top SNPs under selection for genomic prediction of carcass traits in both breeds.

148 Multiple Dysregulated Novel Pathways and Genes in Aleutian Mink Disease Revealed by Selection Signatures and Gene Network Analyses Using Whole-genome Sequence Data

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 76-76
Author(s):  
Seyed Milad Vahedi ◽  
Karim Karimi ◽  
Siavash Salek Ardestani ◽  
Younes Miar
Keyword(s):  
Sequence Data ◽  
American Mink ◽  
Enrichment Analysis ◽  
Whole Genome Sequence ◽  
Fixation Index ◽  
Pathway Enrichment Analysis ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Network Analyses ◽  
Genome Level

Abstract Aleutian disease (AD) is a chronic persistent infection in domestic mink caused by Aleutian mink disease virus (AMDV). Female mink’s fertility and pelt quality depression are the main reasons for the AD’s negative economic impacts on the mink industry. A total number of 79 American mink from the Canadian Center for Fur Animal Research at Dalhousie University (Truro, NS, Canada) were classified based on the results of counter immunoelectrophoresis (CIEP) tests into two groups of positive (n = 48) and negative (n = 31). Whole-genome sequences comprising 4,176 scaffolds and 8,039,737 single nucleotide polymorphisms (SNPs) were used to trace the selection footprints for response to AMDV infection at the genome level. Window-based fixation index (Fst) and nucleotide diversity (θπ) statistics were estimated to compare positive and negative animals’ genomes. The overlapped top 1% genomic windows between two statistics were considered as potential regions underlying selection pressures. A total of 98 genomic regions harboring 33 candidate genes were detected as selective signals. Most of the identified genes were involved in the development and functions of immune system (PPP3CA, SMAP2, TNFRSF21, SKIL, and AKIRIN2), musculoskeletal system (COL9A2, PPP1R9A, ANK2, AKAP9, and STRIT1), nervous system (ASCL1, ZFP69B, SLC25A27, MCF2, and SLC7A14), reproductive system (CAMK2D, GJB7, SSMEM1, C6orf163), liver (PAH and DPYD), and lung (SLC35A1). Gene-expression network analysis showed the interactions among 27 identified genes. Moreover, pathway enrichment analysis of the constructed genes network revealed significant oxytocin (KEGG: hsa04921) and GnRH signaling (KEGG: hsa04912) pathways, which are likely to be impaired by AMDV leading to dams’ fecundity reduction. These results provided a perspective to the genetic architecture of response to AD in American mink and novel insight into the pathogenesis of AMDV.

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