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- Rafati, Nima, et al.
(author)
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A genomic map of clinal variation across the European rabbit hybrid zone
- 2018
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In: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 27:6, s. 1457-1478
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Journal article (peer-reviewed)abstract
- Speciation is a process proceeding from weak to complete reproductive isolation. In this continuum, naturally hybridizing taxa provide a promising avenue for revealing the genetic changes associated with the incipient stages of speciation. To identify such changes between two subspecies of rabbits that display partial reproductive isolation, we studied patterns of allele frequency change across their hybrid zone using whole-genome sequencing. To connect levels and patterns of genetic differentiation with phenotypic manifestations of subfertility in hybrid rabbits, we further investigated patterns of gene expression in testis. Geographic cline analysis revealed 253 regions characterized by steep changes in allele frequency across their natural region of contact. This catalog of regions is likely to be enriched for loci implicated in reproductive barriers and yielded several insights into the evolution of hybrid dysfunction in rabbits: (i) incomplete reproductive isolation is likely governed by the effects of many loci, (ii) protein-protein interaction analysis suggest that genes within these loci interact more than expected by chance, (iii) regulatory variation is likely the primary driver of incompatibilities, and (iv) large chromosomal rearrangements appear not to be a major mechanism underlying incompatibilities or promoting isolation in the face of gene flow. We detected extensive misregulation of gene expression in testis of hybrid males, but not a statistical overrepresentation of differentially expressed genes in candidate regions. Our results also did not support an X chromosome-wide disruption of expression as observed in mice and cats, suggesting variation in the mechanistic basis of hybrid male reduced fertility among mammals.
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- Sayyab, Shumaila, et al.
(author)
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A computational method for detection of structural variants using Deviant Reads and read pair Orientation:DevRO
- 2016
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Other publication (other academic/artistic)abstract
- Background Next generation sequencing (NGS) technology has made it possible to perform high-resolution screens for structural variants. Computational methods for detection of structural variants utilize paired-end mapping information, depth of coverage, split reads, or some combination of such data. The available methods are particularly designed to detect structural variants in single genomes or multiple genomes in a pairwise manner. The aim of this study was to develop a bioinformatics pipeline for detection of large structural variants using multiple pooled populations.Results Here we describe the method “DevRO”, developed to enable identification of structural variants using short insert paired-ends and long-range mate-pairs. DevRO uses paired-end mapping information from both types of libraries for identification of inversions, deletions and duplications followed by read depth information to screen for copy number variants. DevRO can detect structural variants in multiple populations without the need for pairwise comparisons. It uses a combined approach based on (i) paired-end mapping and (ii) depth of coverage that gives power to the study as compared to traditional methods that are based on either of these. DevRO is also designed to detect deletions in the reference assembly, which is an added functionality as compared to available methods.Conclusion We report a bioinformatics pipeline “DevRO” for detection of structural variants using paired-end mapping and depth of coverage methods tested on sequencing reads from multiple pooled rabbit populations. This method is useful when large numbers of populations have been re-sequenced as compared to traditional methods that can detect structural variants in a pairwise manner.
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- Sayyab, Shumaila, et al.
(author)
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Whole-Genome Sequencing of a Canine Family Trio Reveals a FAM83G Variant Associated with Hereditary Footpad Hyperkeratosis
- 2016
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In: G3. - : Oxford University Press (OUP). - 2160-1836. ; 6, s. 521-527
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Journal article (peer-reviewed)abstract
- Over 250 Mendelian traits and disorders, caused by rare alleles have been mapped in the canine genome. Although each disease is rare in the dog as a species, they are collectively common and have major impact on canine health. With SNP-based genotyping arrays, genome-wide association studies (GWAS) have proven to be a powerful method to map the genomic region of interest when 10-20 cases and 10-20 controls are available. However, to identify the genetic variant in associated regions, fine-mapping and targeted resequencing is required. Here we present a new approach using whole-genome sequencing (WGS) of a family trio without prior GWAS. As a proof-ofconcept, we chose an autosomal recessive disease known as hereditary footpad hyperkeratosis (HFH) in Kromfohrländer dogs. To our knowledge, this is the first time this family trio WGS-approach has been used successfully to identify a genetic variant that perfectly segregates with a canine disorder. The sequencing of three Kromfohrländer dogs from a family trio (an affected offspring and both its healthy parents) resulted in an average genome coverage of 9.2X per individual. After applying stringent filtering criteria for candidate causative coding variants, 527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences, and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G. C (p.R52P) was found to be concordant in eight additional cases, and 16 healthy Kromfohrländer dogs.
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- Viluma, Agnese, et al.
(author)
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Evaluation of Whole-Genome Sequencing of Four Chinese Crested Dogs for Variant Detection Using the Ion Proton System
- 2015
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In: Canine Genetics and Epidemiology. - : Springer Science and Business Media LLC. - 2052-6687. ; 2
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Journal article (peer-reviewed)abstract
- Background Next generation sequencing (NGS) has traditionally been performed by large genome centers, but in recent years, the costs for whole-genome sequencing (WGS) have decreased substantially. With the introduction of smaller and less expensive "desktop" systems, NGS is now moving into the general laboratory. To evaluate the Ion Proton system for WGS we sequenced four Chinese Crested dogs and analyzed the data quality in terms of genome and exome coverage, the number of detected single nucleotide variants (SNVs) and insertions and deletions (INDELs) and the genotype concordance with the Illumina HD canine SNP array. For each of the four dogs, a 200bp fragment library was constructed from genomic DNA and sequenced on two Ion PI chips per dog to reach mean coverage of 6-8x of the canine genome (genome size ≈ 2.4 Gb). Results On average, each Ion PI chip yielded approximately 73.3 million reads with a mean read length of 130bp (~9.5 Gb sequence data) of which 98.5% could be aligned to the canine reference genome (CanFam3.1). By sequencing a single dog using one fragment library and two Ion PI chips, on average 80% of the genome and 77% exome was covered by at least four reads. After removing duplicate reads (20.7%) the mean coverage across the whole genome was 6x. Using sequence data from all four individuals (four fragment libraries and eight Ion PI chips) the genome and exome coverage could be further increased to 97.2 and 94.3%, respectively. We detected 4.83 million unique SNPs and 6.10 million unique INDEL positions across all individuals. A comparison between SNP genotypes detected with the WGS and the 170K Illumina HD canine SNP array showed 90% concordance. Conclusions We have evaluated whole-genome sequencing on the Ion Proton system for genetic variant detection in four Chinese crested dogs. Even though INDEL calling with Ion Proton data is challenging due to specific platform errors, in case of SNP calling it can serve as an alternative to other next-generation sequencing platforms and SNP genotyping arrays, in studies aiming to identify causative mutations for rare monogenic diseases. In addition, we have identified new genetic variants of the Chinese Crested dog that will contribute to further whole-genome sequencing studies aimed to identify mutations associated with monogenic diseases with autosomal recessive inheritance.
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