Marker enrichment and construction of haplotype-specific BAC contigs for the polyembryony genomic region in Citrus

Abstract Arabidopsis thaliana is a highly selfing plant that nevertheless appears to undergo substantial recombination. To reconcile its selfing habit with the observations of recombination, we have sampled the genetic diversity of A. thaliana at 14 loci of ~500 bp each, spread across 170 kb of genomic sequence centered on a QTL for resistance to herbivory. A total of 170 of the 6321 nucleotides surveyed were polymorphic, with 169 being biallelic. The mean silent genetic diversity (πs) varied between 0.001 and 0.03. Pairwise linkage disequilibria between the polymorphisms were negatively correlated with distance, although this effect vanished when only pairs of polymorphisms with four haplotypes were included in the analysis. The absence of a consistent negative correlation between distance and linkage disequilibrium indicated that gene conversion might have played an important role in distributing genetic diversity throughout the region. We tested this by coalescent simulations and estimate that up to 90% of recombination is due to gene conversion.

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Molecular and Functional Mapping of the Piebald Deletion Complex on Mouse Chromosome 14

Genetics ◽

10.1093/genetics/157.2.803 ◽

2001 ◽

Vol 157 (2) ◽

pp. 803-815

Author(s):

Jeffrey J Roix ◽

Aaron Hagge-Greenberg ◽

Dennis M Bissonnette ◽

Sandra Rodick ◽

Liane B Russell ◽

...

Keyword(s):

Mouse Chromosome ◽

System Development ◽

Genomic Region ◽

Nervous System Development ◽

Chromosome 14 ◽

Developmental Defects ◽

Oak Ridge ◽

Recessive Mutations ◽

Large Deletions ◽

Critical Regions

Abstract The piebald deletion complex is a set of overlapping chromosomal deficiencies surrounding the endothelin receptor B locus collected during the Oak Ridge specific-locus-test mutagenesis screen. These chromosomal deletions represent an important resource for genetic studies to dissect the functional content of a genomic region, and several developmental defects have been associated with mice homozygous for distinct piebald deletion alleles. We have used molecular markers to order the breakpoints for 20 deletion alleles that span a 15.7–18-cM region of distal mouse chromosome 14. Large deletions covering as much as 11 cM have been identified that will be useful for regionally directed mutagenesis screens to reveal recessive mutations that disrupt development. Deletions identified as having breakpoints positioned within previously described critical regions have been used in complementation studies to further define the functional intervals associated with the developmental defects. This has focused our efforts to isolate genes required for newborn respiration and survival, skeletal patterning and morphogenesis, and central nervous system development.

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Genome-Wide Association Study (GWAS) for Examining the Genomics Controlling Prickle Production in Red Raspberry (Rubus idaeus L.)

Agronomy ◽

10.3390/agronomy11010027 ◽

2020 ◽

Vol 11 (1) ◽

pp. 27

Author(s):

Archana Khadgi ◽

Courtney A. Weber

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Genomic Region ◽

Rubus Idaeus ◽

Genome Wide Association ◽

Nucleotide Polymorphisms ◽

Red Raspberry ◽

Genome Wide ◽

A Genome ◽

Genotype By Sequencing

Red raspberry (Rubus idaeus L.) is an expanding high-value berry crop worldwide. The presence of prickles, outgrowths of epidermal tissues lacking vasculature, on the canes, petioles, and undersides of leaves complicates both field management and harvest. The utilization of cultivars with fewer prickles or prickle-free canes simplifies production. A previously generated population segregating for prickles utilizing the s locus between the prickle-free cultivar Joan J (ss) and the prickled cultivar Caroline (Ss) was analyzed to identify the genomic region associated with prickle development in red raspberry. Genotype by sequencing (GBS) was combined with a genome-wide association study (GWAS) using fixed and random model circulating probability unification (FarmCPU) to analyze 8474 single nucleotide polymorphisms (SNPs) and identify significant markers associated with the prickle-free trait. A total of four SNPs were identified on chromosome 4 that were associated with the phenotype and were located near or in annotated genes. This study demonstrates how association genetics can be used to decipher the genetic control of important horticultural traits in Rubus, and provides valuable information about the genomic region and potential genes underlying the prickle-free trait.

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An FGA Frameshift Variant Associated with Afibrinogenemia in Dachshunds

Genes ◽

10.3390/genes12071065 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1065

Author(s):

Reinhard Mischke ◽

Julia Metzger ◽

Ottmar Distl

Keyword(s):

Protein Sequence ◽

Sanger Sequencing ◽

Selective Breeding ◽

Genome Wide Association Study ◽

Frameshift Mutation ◽

Homozygosity Mapping ◽

Genomic Region ◽

Severe Bleeding ◽

Genome Wide ◽

A Genome

Congenital fibrinogen disorders are very rare in dogs. Cases of afibrinogenemia have been reported in Bernese Mountain, Bichon Frise, Cocker Spaniel, Collie, Lhasa Apso, Viszla, and St. Bernard dogs. In the present study, we examined four miniature wire-haired Dachshunds with afibrinogenemia and ascertained their pedigree. Homozygosity mapping and a genome-wide association study identified a candidate genomic region at 50,188,932–64,187,680 bp on CFA15 harboring FGB (fibrinogen beta chain), FGA (fibrinogen alpha chain), and FGG (fibrinogen gamma-B chain). Sanger sequencing of all three fibrinogen genes in two cases and validation of the FGA-associated mutation (FGA:g.6296delT, NC_006597.3:g.52240694delA, rs1152388481) in pedigree members showed a perfect co-segregation with afibrinogenemia-affected phenotypes, obligate carriers, and healthy animals. In addition, the rs1152388481 variant was validated in 393 Dachshunds and samples from 33 other dog breeds. The rs1152388481 variant is predicted to modify the protein sequence of both FGA transcripts (FGA201:p.Ile486Met and FGA-202:p.Ile555Met) leading to proteins truncated by 306 amino acids. The present data provide evidence for a novel FGA truncating frameshift mutation that is very likely to explain the cases of severe bleeding due to afibrinogenemia in a Dachshund family. This mutation has already been spread in Dachshunds through carriers before cases were ascertained. Genetic testing allows selective breeding to prevent afibrinogenemia-affected puppies in the future.

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white+ Transgene Insertions Presenting a Dorsal/Ventral Pattern Define a Single Cluster of Homeobox Genes That Is Silenced by the Polycomb-group Proteins in Drosophila melanogaster

Genetics ◽

10.1093/genetics/149.1.257 ◽

1998 ◽

Vol 149 (1) ◽

pp. 257-275 ◽

Cited By ~ 4

Author(s):

Sophie Netter ◽

Marie-Odile Fauvarque ◽

Ruth Diez del Corral ◽

Jean-Maurice Dura ◽

Dario Coen

Keyword(s):

Chromatin Structure ◽

Target Genes ◽

Position Effect ◽

Phenotypic Expression ◽

Positional Information ◽

Genomic Region ◽

Polycomb Group ◽

Position Effect Variegation ◽

Trithorax Group ◽

Clear Cut

AbstractWe used the white gene as an enhancer trap and reporter of chromatin structure. We collected white+ transgene insertions presenting a peculiar pigmentation pattern in the eye: white expression is restricted to the dorsal half of the eye, with a clear-cut dorsal/ventral (D/V) border. This D/V pattern is stable and heritable, indicating that phenotypic expression of the white reporter reflects positional information in the developing eye. Localization of these transgenes led us to identify a unique genomic region encompassing 140 kb in 69D1–3 subject to this D/V effect. This region contains at least three closely related homeobox-containing genes that are constituents of the iroquois complex (IRO-C). IRO-C genes are coordinately regulated and implicated in similar developmental processes. Expression of these genes in the eye is regulated by the products of the Polycomb -group (Pc-G) and trithorax-group (trx-G) genes but is not modified by classical modifiers of position-effect variegation. Our results, together with the report of a Pc -G binding site in 69D, suggest that we have identified a novel cluster of target genes for the Pc-G and trx-G products. We thus propose that ventral silencing of the whole IRO-C in the eye occurs at the level of chromatin structure in a manner similar to that of the homeotic gene complexes, perhaps by local compaction of the region into a heterochromatin-like structure involving the Pc-G products.

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IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children

Genes and Immunity ◽

10.1038/s41435-021-00127-7 ◽

2021 ◽

Author(s):

Ludmila Prokunina-Olsson ◽

Robert D. Morrison ◽

Adeola Obajemu ◽

Almahamoudou Mahamar ◽

Sungduk Kim ◽

...

Keyword(s):

Respiratory Infections ◽

Genomic Region ◽

First Episode ◽

Genetic Associations ◽

Gastrointestinal Infections ◽

Type Iii ◽

Functional Variants ◽

Younger Age ◽

Increased Risk ◽

Pediatric Infections

AbstractGenetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r2 = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections.

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3D reconstruction of genomic regions from sparse interaction data

NAR Genomics and Bioinformatics ◽

10.1093/nargab/lqab017 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Julen Mendieta-Esteban ◽

Marco Di Stefano ◽

David Castillo ◽

Irene Farabella ◽

Marc A Marti-Renom

Keyword(s):

3D Models ◽

Genomic Region ◽

Gene Promoters ◽

Chromosome Conformation ◽

The Matrix ◽

Chromatin Structural ◽

A Cell ◽

Similar Accuracy ◽

Genomic Regions ◽

Interaction Matrices

Abstract Chromosome conformation capture (3C) technologies measure the interaction frequency between pairs of chromatin regions within the nucleus in a cell or a population of cells. Some of these 3C technologies retrieve interactions involving non-contiguous sets of loci, resulting in sparse interaction matrices. One of such 3C technologies is Promoter Capture Hi-C (pcHi-C) that is tailored to probe only interactions involving gene promoters. As such, pcHi-C provides sparse interaction matrices that are suitable to characterize short- and long-range enhancer–promoter interactions. Here, we introduce a new method to reconstruct the chromatin structural (3D) organization from sparse 3C-based datasets such as pcHi-C. Our method allows for data normalization, detection of significant interactions and reconstruction of the full 3D organization of the genomic region despite of the data sparseness. Specifically, it builds, with as low as the 2–3% of the data from the matrix, reliable 3D models of similar accuracy of those based on dense interaction matrices. Furthermore, the method is sensitive enough to detect cell-type-specific 3D organizational features such as the formation of different networks of active gene communities.

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Fine scale human genetic structure in three regions of Cameroon reveals episodic diversifying selection

Scientific Reports ◽

10.1038/s41598-020-79124-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kevin K. Esoh ◽

Tobias O. Apinjoh ◽

Steven G. Nyanjom ◽

Ambroise Wonkam ◽

Emile R. Chimusa ◽

...

Keyword(s):

Genetic Structure ◽

Ethnic Groups ◽

Genetic Association ◽

Association Studies ◽

Genetic Association Studies ◽

Genomic Region ◽

Sub Saharan Africa ◽

Genome Wide Association Studies ◽

Fine Scale ◽

Sub Saharan

AbstractInferences from genetic association studies rely largely on the definition and description of the underlying populations that highlight their genetic similarities and differences. The clustering of human populations into subgroups (population structure) can significantly confound disease associations. This study investigated the fine-scale genetic structure within Cameroon that may underlie disparities observed with Cameroonian ethnicities in malaria genome-wide association studies in sub-Saharan Africa. Genotype data of 1073 individuals from three regions and three ethnic groups in Cameroon were analyzed using measures of genetic proximity to ascertain fine-scale genetic structure. Model-based clustering revealed distinct ancestral proportions among the Bantu, Semi-Bantu and Foulbe ethnic groups, while haplotype-based coancestry estimation revealed possible longstanding and ongoing sympatric differentiation among individuals of the Foulbe ethnic group, and their Bantu and Semi-Bantu counterparts. A genome scan found strong selection signatures in the HLA gene region, confirming longstanding knowledge of natural selection on this genomic region in African populations following immense disease pressure. Signatures of selection were also observed in the HBB gene cluster, a genomic region known to be under strong balancing selection in sub-Saharan Africa due to its co-evolution with malaria. This study further supports the role of evolution in shaping genomes of Cameroonian populations and reveals fine-scale hierarchical structure among and within Cameroonian ethnicities that may impact genetic association studies in the country.

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Dynamics of Specific cfDNA Fragments in the Plasma of Full Marathon Participants

Genes ◽

10.3390/genes12050676 ◽

2021 ◽

Vol 12 (5) ◽

pp. 676

Author(s):

Takehito Sugasawa ◽

Shin-ichiro Fujita ◽

Tomoaki Kuji ◽

Noriyo Ishibashi ◽

Kenshirou Tamai ◽

...

Keyword(s):

Exercise Physiology ◽

High Sensitivity ◽

Genomic Region ◽

Qpcr Assay ◽

Strongly Correlated ◽

Healthy Humans ◽

Blood Cell And Plasma ◽

Next Generation Sequencing Ngs ◽

Taqman Qpcr Assay ◽

Taqman Qpcr

Plasma cell-free DNA (cfDNA) is frequently analyzed using liquid biopsy to investigate cancer markers. We hypothesized that this concept might be applicable in exercise physiology. Here, we aimed to identify specific cfDNA (spcfDNA) sequences in the plasma of healthy humans using next-generation sequencing (NGS) and clearly define the dynamics regarding spcfDNA-fragment levels upon extreme exercises, such as running a full marathon. NGS analysis was performed using cfDNA of pooled plasma collected from healthy participants. We confirmed that the TaqMan-qPCR assay had high sensitivity and found that the spcfDNA sequence abundance was 16,600-fold higher than that in a normal genomic region. We then used the TaqMan-qPCR assay to investigate the dynamics of spcfDNA-fragment levels upon running a full marathon. The spcfDNA fragment levels were significantly increased post-marathon. Furthermore, spcfDNA fragment levels were strongly correlated with white blood cell and plasma myoglobin concentrations. These results suggest the spcfDNA fragments identified in this study were highly sensitive as markers of extreme physical stress. The findings of this study may provide new insights into exercise physiology and genome biology in humans.

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