scholarly journals A de novo frameshift mutation in ZEB2 causes polledness, abnormal skull shape, small body stature and subfertility in Fleckvieh cattle

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lilian J. Gehrke ◽  
Maulik Upadhyay ◽  
Kristin Heidrich ◽  
Elisabeth Kunz ◽  
Daniela Klaus-Halla ◽  
...  
Keyword(s):  
De Novo ◽  
Small Body ◽  
Protein Product ◽  
Whole Genome Sequencing Data ◽  
Chromosome 2 ◽  
Sequencing Data ◽  
Autosomal Dominant Trait ◽  
Intergenic Regions ◽  
Body Stature ◽  
Growth Of Animals

Abstract Polledness in cattle is an autosomal dominant trait. Previous studies have revealed allelic heterogeneity at the polled locus and four different variants were identified, all in intergenic regions. In this study, we report a case of polled bull (FV-Polled1) born to horned parents, indicating a de novo origin of this polled condition. Using 50K genotyping and whole genome sequencing data, we identified on chromosome 2 an 11-bp deletion (AC_000159.1:g.52364063_52364073del; Del11) in the second exon of ZEB2 gene as the causal mutation for this de novo polled condition. We predicted that the deletion would shorten the protein product of ZEB2 by almost 91%. Moreover, we showed that all animals carrying Del11 mutation displayed symptoms similar to Mowat-Wilson syndrome (MWS) in humans, which is also associated with genetic variations in ZEB2. The symptoms in cattle include delayed maturity, small body stature and abnormal shape of skull. This is the first report of a de novo dominant mutation affecting only ZEB2 and associated with a genetic absence of horns. Therefore our results demonstrate undoubtedly that ZEB2 plays an important role in the process of horn ontogenesis as well as in the regulation of overall development and growth of animals.

scholarly journals Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Clémentine Escouflaire ◽  
Emmanuelle Rebours ◽  
Mathieu Charles ◽  
Sébastien Orellana ◽  
Margarita Cano ◽  
...  
Keyword(s):  
Ectodermal Dysplasia ◽  
De Novo ◽  
Genetic Disorder ◽  
Hair Follicles ◽  
Whole Genome Sequencing Data ◽  
Recessive Mutation ◽  
Sources Of Information ◽  
Affected Animal ◽  
Sequencing Data ◽  
Hypohidrotic Ectodermal Dysplasia

Abstract Background In mammals, hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that is characterized by sparse hair, tooth abnormalities, and defects in cutaneous glands. Only four genes, EDA, EDAR, EDARADD and WNT10A account for more than 90% of HED cases, and EDA, on chromosome X, is involved in 50% of the cases. In this study, we explored an isolated case of a female Holstein calf with symptoms similar to HED. Results Clinical examination confirmed the diagnosis. The affected female showed homogeneous hypotrichosis and oligodontia as previously observed in bovine EDAR homozygous and EDA hemizygous mutants. Under light microscopy, the hair follicles were thinner and located higher in the dermis of the frontal skin in the affected animal than in the control. Moreover, the affected animal showed a five-fold increase in the number of hair follicles and a four-fold decrease in the diameter of the pilary canals. Pedigree analysis revealed that the coefficient of inbreeding of the affected calf (4.58%) was not higher than the average population inbreeding coefficient (4.59%). This animal had ten ancestors in its paternal and maternal lineages. By estimating the number of affected cases that would be expected if any of these common ancestors carried a recessive mutation, we concluded that, if they existed, other cases of HED should have been reported in France, which is not the case. Therefore, we assumed that the causal mutation was dominant and de novo. By analyzing whole-genome sequencing data, we identified a large chromosomal inversion with breakpoints located in the first introns of the EDA and XIST genes. Genotyping by PCR-electrophoresis the case and its parents allowed us to demonstrate the de novo origin of this inversion. Finally, using various sources of information we present a body of evidence that supports the hypothesis that this mutation is responsible for a skewed inactivation of X, and that only the normal X can be inactivated. Conclusions In this article, we report a unique case of X-linked HED affected Holstein female calf with an assumed full inactivation of the normal X-chromosome, thus leading to a severe phenotype similar to that of hemizygous males.

scholarly journals De novo indels within introns contribute to ASD incidence

2017 ◽  
Author(s):  
Adriana Munoz ◽  
Boris Yamrom ◽  
Yoon-ha Lee ◽  
Peter Andrews ◽  
Steven Marks ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Target Genes ◽  
De Novo ◽  
Whole Genome Sequencing Data ◽  
P Value ◽  
Whole Genome ◽  
Sequencing Data ◽  
Control Sets ◽  
The Difference

AbstractCopy number profiling and whole-exome sequencing has allowed us to make remarkable progress in our understanding of the genetics of autism over the past ten years, but there are major aspects of the genetics that are unresolved. Through whole-genome sequencing, additional types of genetic variants can be observed. These variants are abundant and to know which are functional is challenging. We have analyzed whole-genome sequencing data from 510 of the Simons Simplex Collections quad families and focused our attention on intronic variants. Within the introns of 546 high-quality autism target genes, we identified 63 de novo indels in the affected and only 37 in the unaffected siblings. The difference of 26 events is significantly larger than expected (p-val = 0.01) and using reasonable extrapolation shows that de novo intronic indels can contribute to at least 10% of simplex autism. The significance increases if we restrict to the half of the autism targets that are intolerant to damaging variants in the normal human population, which half we expect to be even more enriched for autism genes. For these 273 targets we observe 43 and 20 events in affected and unaffected siblings, respectively (p-value of 0.005). There was no significant signal in the number of de novo intronic indels in any of the control sets of genes analyzed. We see no signal from de novo substitutions in the introns of target genes.

scholarly journals Leaf form diversification in an heirloom tomato results from alterations in two different HOMEOBOX genes

2020 ◽  
Author(s):  
Hokuto Nakayama ◽  
Steven D. Rowland ◽  
Zizhang Cheng ◽  
Kristina Zumstein ◽  
Julie Kang ◽  
...  
Keyword(s):  
Gene Network ◽  
Natural Variation ◽  
De Novo ◽  
Whole Genome Sequencing Data ◽  
Phenotypic Traits ◽  
Comparative Genome Analysis ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Leaf Phenotype ◽  
Gene Network Analysis

AbstractDomesticated plants and animals display tremendous diversity in various phenotypic traits and often this diversity is seen within the same species. Tomato (Solanum lycopersicum; Solanaceae) cultivars show wide variation in leaf morphology, but the influence of breeding efforts in sculpting this diversity is not known. Here, we demonstrate that a single nucleotide deletion in the homeobox motif of BIPINNATA, which is a BEL-LIKE HOMEODOMAIN gene, led to a highly complex leaf phenotype in an heirloom tomato, Silvery Fir Tree (SiFT). Additionally, a comparative gene network analysis revealed that reduced expression of the ortholog of WUSCHEL RELATED HOMEOBOX 1 is also important for the narrow leaflet phenotype seen in SiFT. Phylogenetic and comparative genome analysis using whole-genome sequencing data suggests that the bip mutation in SiFT is likely a de novo mutation, instead of standing genetic variation. These results provide new insights into natural variation in phenotypic traits introduced into crops during improvement processes after domestication.

scholarly journals The genetic origin of evolidine, the first cyclopeptide discovered in plants, and related orbitides

2020 ◽  
Vol 295 (42) ◽  
pp. 14510-14521 ◽  
Author(s):  
Mark F. Fisher ◽  
Colton D. Payne ◽  
Thaveshini Chetty ◽  
Darren Crayn ◽  
Oliver Berkowitz ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
De Novo ◽  
Forest Tree ◽  
Whole Genome Sequencing Data ◽  
The Novel ◽  
Rna Seq ◽  
Sequencing Data ◽  
The Family

Cyclic peptides are reported to have antibacterial, antifungal, and other bioactivities. Orbitides are a class of cyclic peptides that are small, head-to-tail cyclized, composed of proteinogenic amino acids and lack disulfide bonds; they are also known in several genera of the plant family Rutaceae. Melicope xanthoxyloides is the Australian rain forest tree of the Rutaceae family in which evolidine, the first plant cyclic peptide, was discovered. Evolidine (cyclo-SFLPVNL) has subsequently been all but forgotten in the academic literature, so to redress this we used tandem MS and de novo transcriptomics to rediscover evolidine and decipher its biosynthetic origin from a short precursor just 48 residues in length. We also identified another six M. xanthoxyloides orbitides using the same techniques. These peptides have atypically diverse C termini consisting of residues not recognized by either of the known proteases plants use to macrocyclize peptides, suggesting new cyclizing enzymes await discovery. We examined the structure of two of the novel orbitides by NMR, finding one had a definable structure, whereas the other did not. Mining RNA-seq and whole genome sequencing data from other species of the Rutaceae family revealed that a large and diverse family of peptides is encoded by similar sequences across the family and demonstrates how powerful de novo transcriptomics can be at accelerating the discovery of new peptide families.

scholarly journals Whole genome sequencing data of multiple individuals of Pakistani descent

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Shahid Y. Khan ◽  
Muhammad Ali ◽  
Mei-Chong W. Lee ◽  
Zhiwei Ma ◽  
Pooja Biswas ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Sequence Data ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Asian Populations ◽  
Ethnic Populations ◽  
Novel Variants ◽  
Intergenic Regions

Abstract Here we report whole genome sequencing of four individuals (H3, H4, H5, and H6) from a family of Pakistani descent. Whole genome sequencing yielded 1084.92, 894.73, 1068.62, and 1005.77 million mapped reads corresponding to 162.73, 134.21, 160.29, and 150.86 Gb sequence data and 52.49x, 43.29x, 51.70x, and 48.66x average coverage for H3, H4, H5, and H6, respectively. We identified 3,529,659, 3,478,495, 3,407,895, and 3,426,862 variants in the genomes of H3, H4, H5, and H6, respectively, including 1,668,024 variants common in the four genomes. Further, we identified 42,422, 39,824, 28,599, and 35,206 novel variants in the genomes of H3, H4, H5, and H6, respectively. A major fraction of the variants identified in the four genomes reside within the intergenic regions of the genome. Single nucleotide polymorphism (SNP) genotype based comparative analysis with ethnic populations of 1000 Genomes database linked the ancestry of all four genomes with the South Asian populations, which was further supported by mitochondria based haplogroup analysis. In conclusion, we report whole genome sequencing of four individuals of Pakistani descent.

scholarly journals CaMuS: simultaneous fitting and de novo imputation of cancer mutational signature

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria Cartolano ◽  
Nima Abedpour ◽  
Viktor Achter ◽  
Tsun-Po Yang ◽  
Sandra Ackermann ◽  
...  
Keyword(s):  
De Novo ◽  
Probability Distributions ◽  
Simulated Data ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Mutational Signatures ◽  
Computational Performance ◽  
Reliable Parameter ◽  
Similar Accuracy ◽  
Mutational Processes

Abstract The identification of the mutational processes operating in tumour cells has implications for cancer diagnosis and therapy. These processes leave mutational patterns on the cancer genomes, which are referred to as mutational signatures. Recently, 81 mutational signatures have been inferred using computational algorithms on sequencing data of 23,879 samples. However, these published signatures may not always offer a comprehensive view on the biological processes underlying tumour types that are not included or underrepresented in the reference studies. To circumvent this problem, we designed CaMuS (Cancer Mutational Signatures) to construct de novo signatures while simultaneously fitting publicly available mutational signatures. Furthermore, we propose to estimate signature similarity by comparing probability distributions using the Hellinger distance. We applied CaMuS to infer signatures of mutational processes in poorly studied cancer types. We used whole genome sequencing data of 56 neuroblastoma, thus providing evidence for the versatility of CaMuS. Using simulated data, we compared the performance of CaMuS to sigfit, a recently developed algorithm with comparable inference functionalities. CaMuS and sigfit reconstructed the simulated datasets with similar accuracy; however two main features may argue for CaMuS over sigfit: (i) superior computational performance and (ii) a reliable parameter selection method to avoid spurious signatures.

scholarly journals Draft genome assemblies using sequencing reads from Oxford Nanopore Technology and Illumina platforms for four species of North American Fundulus killifish

GigaScience ◽  
2020 ◽  
Vol 9 (6) ◽  
Author(s):  
Lisa K Johnson ◽  
Ruta Sahasrabudhe ◽  
James Anthony Gill ◽  
Jennifer L Roach ◽  
Lutz Froenicke ◽  
...  
Keyword(s):  
North American ◽  
De Novo ◽  
Draft Genome ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Sequence Coverage ◽  
Short Read ◽  
Oxford Nanopore ◽  
Long Read ◽  
Genome Assemblies

Abstract Background Whole-genome sequencing data from wild-caught individuals of closely related North American killifish species (Fundulus xenicus, Fundulus catenatus, Fundulus nottii, and Fundulus olivaceus) were obtained using long-read Oxford Nanopore Technology (ONT) PromethION and short-read Illumina platforms. Findings Draft de novo reference genome assemblies were generated using a combination of long and short sequencing reads. For each species, the PromethION platform was used to generate 30–45× sequence coverage, and the Illumina platform was used to generate 50–160× sequence coverage. Illumina-only assemblies were fragmented with high numbers of contigs, while ONT-only assemblies were error prone with low BUSCO scores. The highest N50 values, ranging from 0.4 to 2.7 Mb, were from assemblies generated using a combination of short- and long-read data. BUSCO scores were consistently >90% complete using the Eukaryota database. Conclusions High-quality genomes can be obtained from a combination of using short-read Illumina data to polish assemblies generated with long-read ONT data. Draft assemblies and raw sequencing data are available for public use. We encourage use and reuse of these data for assembly benchmarking and other analyses.

scholarly journals Divergence and introgression among the virilis group of Drosophila

2022 ◽  
Author(s):  
Leeban Yusuf ◽  
Venera Tyukmaeva ◽  
Anneli Hoikkala ◽  
Michael G Ritchie
Keyword(s):  
Gene Flow ◽  
Related Species ◽  
De Novo ◽  
Phylogenetic Reconstruction ◽  
Sequence Divergence ◽  
Sexual Isolation ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Closely Related Species ◽  
Virilis Group

Speciation with gene flow is now widely regarded as common. However, the frequency of introgression between recently diverged species and the evolutionary consequences of gene flow are still poorly understood. The virilis group of Drosophila contains around a dozen species that are geographically widespread and show varying levels of pre-zygotic and post-zygotic isolation. Here, we utilize de novo genome assemblies and whole-genome sequencing data to resolve phylogenetic relationships and describe patterns of introgression and divergence across the group. We suggest that the virilis group consists of three, rather than the traditional two, subgroups. We found evidence of pervasive phylogenetic discordance caused by ancient introgression events between distant lineages within the group, and much more recent gene flow between closely-related species. When assessing patterns of genome-wide divergence in species pairs across the group, we found no consistent genomic evidence of a disproportionate role for the X chromosome. Some genes undergoing rapid sequence divergence across the group were involved in chemical communication and may be related to the evolution of sexual isolation. We suggest that gene flow between closely-related species has potentially had an impact on lineage-specific adaptation and the evolution of reproductive barriers. Our results show how ancient and recent introgression confuse phylogenetic reconstruction, and suggest that shared variation can facilitate adaptation and speciation.

scholarly journals The genetic origin of evolidine, the first cyclopeptide discovered in plants, and related orbitides

2020 ◽  
Author(s):  
Mark F. Fisher ◽  
Colton Payne ◽  
Thaveshini Chetty ◽  
Darren Crayn ◽  
Oliver Berkowitz ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
De Novo ◽  
Forest Tree ◽  
Whole Genome Sequencing Data ◽  
Resonance Spectroscopy ◽  
The Novel ◽  
Rna Seq ◽  
Sequencing Data

AbstractCyclic peptides are reported to have antibacterial, antifungal and other bioactivities. Several genera of the Rutaceae family are known to produce orbitides, which are small head-to-tail cyclic peptides composed of proteinogenic amino acids and lacking disulfide bonds. Melicope xanthoxyloides is an Australian rain forest tree of the Rutaceae family in which evolidine - the first plant cyclic peptide - was discovered. Evolidine (cyclo-SFLPVNL) has subsequently been all but forgotten in the academic literature, but here we use tandem mass spectrometry to rediscover evolidine and using de novo transcriptomics we show its biosynthetic origin to be from a short precursor just 48 residues in length. In all, seven M. xanthoxyloides orbitides were found and they had atypically diverse C-termini consisting of residues not recognized by either of the known proteases plants use to macrocyclize peptides. Two of the novel orbitides were studied by nuclear magnetic resonance spectroscopy and although one had definable structure, the other did not. By mining RNA-seq and whole genome sequencing data from other species, it was apparent that a large and diverse family of peptides is encoded by sequences like these across the Rutaceae.

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