Duplicated Region Research Articles

Türkiye'de Duchenne/Becker Musküler Distrofisi Kohortunda Distrofin Gen Delesyonları ve Duplikasyonlarının Dağılımı

Duchenne Muscular Dystrophy (DMD) is the most prevalent muscle disease in children, and unfortunately, currently there are no effective treatments for either DMD or Becker Muscular Dystrophy (BMD). Nevertheless, targeted gene therapy treatments have recently emerged, and genetic diagnoses is now the basis of treatment. In addition, genetic and prenatal diagnosis have significantly reduced the incidence rates of these diseases. The aim of this study was to identify the most common deletion and duplication regions in the Turkish population using the Multiplex Ligation-dependent Probe Amplification (MLPA) method, as well as to determine the suitability of patients for current treatments and identify new treatment target regions based on the findings. In clinical practice, data from 103 patients with Duchenne and Becker muscular dystrophy who have been identified with the deletion/duplication using the Multiplex Ligation-dependent Probe Amplification (MLPA) method, as well as 35 participants carrying the deletion/duplication for these diseases, were analyzed. The aim was to detect the most common deletion/duplication regions of the Dystrophin gene in the Turkish population. The majority of patients had deletions (89.9% in males and 75% in females), while a smaller percentage had duplications. The most common deletions occurred in exons 50 and 49, while the most common duplication was in exon 7. The deletions in exons 45-52 accounted for over half of all deletions, and most deletions involved 5 or less exons. The longest deletions involved 30 exons and were found in 2 patients. The findings of this research have provided valuable insights into the prevalence of deletions and duplications in the dystrophin gene among individuals in our population. The results indicate that a significant proportion of patients may be eligible for treatments that are not yet widely available. This study highlights the critical role of population-specific data in advancing the field of dystrophin gene-based therapies.

Novel tRNA Gene Rearrangements in the Mitochondrial Genomes of Poneroid Ants and Phylogenetic Implication of Paraponerinae (Hymenoptera: Formicidae).

Ants (Formicidae) are the most diverse eusocial insects in Hymenoptera, distributed across 17 extant subfamilies grouped into 3 major clades, the Formicoid, Leptanilloid, and Poneroid. While the mitogenomes of Formicoid ants have been well studied, there is a lack of published data on the mitogenomes of Poneroid ants, which requires further characterization. In this study, we first present three complete mitogenomes of Poneroid ants: Paraponera clavata, the only extant species from the subfamily Paraponerinae, and two species (Harpegnathos venator and Buniapone amblyops) from the Ponerinae subfamily. Notable novel gene rearrangements were observed in the new mitogenomes, located in the gene blocks CR-trnM-trnI-trnQ-ND2, COX1-trnK-trnD-ATP8, and ND3-trnA-trnR-trnN-trnS1-trnE-trnF-ND5. We reported the duplication of tRNA genes for the first time in Formicidae. An extra trnQ gene was identified in H. venator. These gene rearrangements could be explained by the tandem duplication/random loss (TDRL) model and the slipped-strand mispairing model. Additionally, one large duplicated region containing tandem repeats was identified in the control region of P. clavata. Phylogenetic analyses based on protein-coding genes and rRNA genes via maximum likelihood and Bayes methods supported the monophyly of the Poneroid clade and the sister group relationship between the subfamilies Paraponerinae and Amblyoponinae. However, caution is advised in interpreting the positions of Paraponerinae due to the potential artifact of long-branch attraction.

Nondisjunction in Trisomy 21: Origin and Mechanisms

Down’s Syndrome is a chromosomal abnormality with a gain of a third copy of chromosome 21, characterized by craniofacial abnormalities, intellectual developmental delay and growth retardation. In the present study, one-day-old neonate and a patient with an aborted fetus were presented to rule out genetic aberrations via CMA screening. DNA was extracted using from the case samples and evaluated by CMA Affymetrix platform. Chromosomal abnormalities in the fetus such as trisomy emerges due to several factors including maternal age, genetic mutational events, non-disjunction of chromosomes and epigenetic changes. Genetic Cause of trisomy 21 is chromosomal aneuploidy and gain of three copies of chromosome 21. The Trisomy 21 can occur due to Robertsonian translocation, Mosaicisms or duplication of critical region of chromosome 21. The trisomy 21 is the result of nondisjunction of homologous chromosomes 21 during gametogenesis at the time of embryo development. CMA is an effective molecular diagnostic tool for predicting and diagnosing chromosomal abnormalities which needs to be promoted in India for healthy pregnancy outcomes. We report two cases of confirmed post-natal Trisomy 21. The main aim of this study is to focus on genetic diagnosis and its awareness which is still lacking with 100% coverage, in developing countries to reduce the burden of genetic diseases and associated emotional and economic consequences.

Comparative Analysis of Techniques Used to Detect Copy-Move Tampering for Real-World Electronic Images

Evolution of high computational powerful computers, easy availability of several innovative editing software package and high-definition quality-based image capturing tools follows to effortless result in producing image forgery. Though, threats for security and misinterpretation of digital images and scenes have been observed to be happened since a long period and also a lot of research has been established in developing diverse techniques to authenticate the digital images. On the contrary, the research in this region is not limited to checking the validity of digital photos but also to exploring the specific signs of distortion or forgery. This analysis would not require additional prior information of intrinsic content of corresponding digital image or prior embedding of watermarks. In this paper, recent growth in the area of copy-move tampering identification have been discussed along with benchmarking study. In this study, three combination of methods like discrete cosine transform with Fast K-Means, discrete wavelet transform with Fast K-Means and discrete cosine transform with Fuzzy-C means can efficiently locate duplicated regions with quantitative parameter i.e. 92%, 83% and 92% respectively. With variety of methodologies and concepts, different applications of forgery detection have been discussed with corresponding outcomes especially using machine and deep learning methods in order to develop efficient automated forgery detection system. The future applications and development of advanced soft-computing based techniques in digital image forgery tampering has been discussed.

A near-complete assembly of asparagus bean provides insights into anthocyanin accumulation in pods.

Asparagus bean (Vigna unguiculata ssp. sesquipedialis), a subspecies of V. unguiculata, is a vital legume crop widely cultivated in Asia for its tender pods consumed as vegetables. However, the existing asparagus bean assemblies still contain numerous gaps and unanchored sequences, which presents challenges to functional genomics research. Here, we present an improved reference genome sequence of an elite asparagus bean variety, Fengchan 6, achieved through the integration of nanopore ultra-long reads, PacBio high-fidelity reads, and Hi-C technology. The improved assembly is 521.3 Mb in length and demonstrates several enhancements, including a higher N50 length (46.4 Mb), an anchor ratio of 99.8%, and the presence of only one gap. Furthermore, we successfully assembled 14 telomeres and all 11 centromeres, including four telomere-to-telomere chromosomes. Remarkably, the centromeric regions cover a total length of 38.1 Mb, providing valuable insights into the complex architecture of centromeres. Among the 30 594 predicted protein-coding genes, we identified 2356 genes that are tandemly duplicated in segmental duplication regions. These findings have implications for defence responses and may contribute to evolutionary processes. By utilizing the reference genome, we were able to effectively identify the presence of the gene VuMYB114, which regulates the accumulation of anthocyanins, thereby controlling the purple coloration of the pods. This discovery holds significant implications for understanding the underlying mechanisms of color determination and the breeding process. Overall, the highly improved reference genome serves as crucial resource and lays a solid foundation for asparagus bean genomic studies and genetic improvement efforts.

Bioinformatic analysis the expression and clinical significance of CDRT15 in cholangiocarcinoma using TCGA database.

Cholangiocarcinoma (CCA) is a common and lethal malignant tumor originating from bile duct epithelial cells. Various tumor biomarkers have been used for its clinical screening, such as carbohydrate antigen 19-9 and carcinoembryonic antigen. This study aimed to demonstrate the value of associated genes-CMT1A duplicated region transcript 15 (CDRT15) for prognosis of CCA by integrated bioinformatics analysis. We obtained CDRT15 expression data and clinical information on patients with CCA from The Cancer Genome Atlas database. Then, we processed the data by differentially expressed gene analysis, gene set enrichment analysis, statistical analysis, etc. Gene Ontology enrichment analysis was aimed to explore the function of gene-related proteins. Single-sample gene set enrichment analysis was used to analyze the correlation between CDRT15 and immune cells. Finally, we constructed the nomogram to predict the prognosis of patients with CCA. The analysis of data in The Cancer Genome Atlas database revealed that CDRT15 was overexpressed in CCA tissues. We performed the interrelation analysis of immune infiltration, showing that CDRT15 are mainly associated with the immune/inflammatory response. ROC curve showed that CDRT15 can be a diagnostic marker of CCA. Subsequently, the prognostic analysis showed that the high expression of CDRT15 was correlated with the poor OS, and patients with high CDRT15 expression may have a poor prognosis. CDRT15 is more highly expressed in CCA, thus we identified that CDRT15 could be an efficient biomarker for patients. CDRT15 expression was negatively correlated with prognosis of CCA. CDRT15 may be involved in the immune infiltration process of CCA.

Boosting variant-calling performance with multi-platform sequencing data using Clair3-MP

BackgroundWith the continuous advances in third-generation sequencing technology and the increasing affordability of next-generation sequencing technology, sequencing data from different sequencing technology platforms is becoming more common. While numerous benchmarking studies have been conducted to compare variant-calling performance across different platforms and approaches, little attention has been paid to the potential of leveraging the strengths of different platforms to optimize overall performance, especially integrating Oxford Nanopore and Illumina sequencing data.ResultsWe investigated the impact of multi-platform data on the performance of variant calling through carefully designed experiments with a deep learning-based variant caller named Clair3-MP (Multi-Platform). Through our research, we not only demonstrated the capability of ONT-Illumina data for improved variant calling, but also identified the optimal scenarios for utilizing ONT-Illumina data. In addition, we revealed that the improvement in variant calling using ONT-Illumina data comes from an improvement in difficult genomic regions, such as the large low-complexity regions and segmental and collapse duplication regions. Moreover, Clair3-MP can incorporate reference genome stratification information to achieve a small but measurable improvement in variant calling. Clair3-MP is accessible as an open-source project at: https://github.com/HKU-BAL/Clair3-MP.ConclusionsThese insights have important implications for researchers and practitioners alike, providing valuable guidance for improving the reliability and efficiency of genomic analysis in diverse applications.

The Alfin-like transcription factors: Identification, characterization, and expression analysis in Pyrus bretschenedri provide insight into its divergent functions on abiotic response

In the previous decades, numerous investigations have been done that the Alfin-like (AL) transcription factors (TFs) are participating in several physiological and development processes in plants including root hair elongation, development of root and meristem, etc. Although the AL-TFs had been comprehensively evaluated in several species, the little finding is reported on the AL-TFs in Chinese pear (Pyrus bretschenedri). In the current study, 15 PbAL genes were systemically characterized and nomenclature as PbAL1 to PbAL15 corresponding to their chromosomal localization. Phylogeny analysis and structural features revealed that the 15 genes could be classified into six subfamilies (S-I to S-VI).Whole-genome duplication (WGD) events are the most common mechanism and may play a crucial role in the expansion of the AL gene family. Microsynteny analysis among Pyrus bretschenedri, Fragaria vesca, Prunus avium, Prunus mume, and Prunus persica showed that AL duplicated regions were more conserved and undergo purifying selection during the evolutionary process. Further analysis of introns-exons, physicochemical properties, and conserved motif showed their functional divergence, diversification in quantity, and structure. The expression pattern of PbAL gene family in various organs and different fruit development stages were conducted through transcriptomic data. Moreover, stress-related cis-acting elements of PbAL genes were found on the promoters regions to be associated with hormonal and environmental stress responses. Noticeably, the expression patterns evaluated by qRT-PCR demonstrated that PbAL genes were differentially expressed under indole acetic acid (IAA), Gibberellic acid (GA), Melatonin (ME) and abscisic acid (ABA) treatment, which response to abiotic stress and fruit growth development. Current work explored the potential function and evolution of PbAL genes in Pyrus bretschenedri. PbAL were investigated as candidate genes for further research and important clues for improving fruit quality through molecular breeding.

Evolution of the spinach sex-linked region within a rarely recombining pericentromeric region.

Sex chromosomes have evolved independently in many different plant lineages. Here, we describe reference genomes for spinach (Spinacia oleracea) X and Y haplotypes by sequencing homozygous XX females and YY males. The long arm of the 185 Mb chromosome 4 carries a 13 Mb X-linked region (XLR) and 24.1 Mb Y-linked region (YLR), of which 10 Mb is Y-specific. We describe evidence that this reflects insertions of autosomal sequences creating a "Y duplication region" or "YDR" whose presence probably directly reduces genetic recombination in the immediately flanking regions, although both the X and Y Sex-Linked Regions are within a large pericentromeric region of chromosome 4 that recombines rarely in meiosis of both sexes. Sequence divergence estimates using synonymous sites indicate that YDR genes started diverging from their likely autosomal progenitors about 3 MYA, around the time when the flanking YLR stopped recombining with the XLR. These flanking regions have a higher density of repetitive sequences in the YY than the XX assembly and include slightly more pseudogenes compared with the XLR, and the YLR has lost about 11% of the ancestral genes, suggesting some degeneration. Insertion of a male-determining factor would have caused Y-linkage across the entire pericentromeric region, creating physically small, highly recombining, terminal pseudo-autosomal regions. These findings provide a broader understanding of the origin of sex chromosomes in spinach.

Characterization of large-scale genomic differences in the first complete human genome

BackgroundThe first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release is a milestone in human genomics. The T2T-CHM13 genome assembly extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. The current human genome reference (GRCh38) has been widely used in various human genomic studies. However, the large-scale genomic differences between these two important genome assemblies are not characterized in detail yet.ResultsHere, in addition to the previously reported “non-syntenic” regions, we find 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool called SynPlotter. The discrepant regions (~ 21.6 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where the deletions or duplications are likely associated with various human diseases, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region—the KLRC gene cluster—show that the depletion of KLRC2 by a single-deletion event is associated with natural killer cell differentiation in ~ 20% of humans. Meanwhile, the rapid amino acid replacements observed within KLRC3 are probably a result of natural selection in primate evolution.ConclusionOur study provides a foundation for understanding the large-scale structural genomic differences between the two crucial human reference genomes, and is thereby important for future human genomics studies.

Changes in social behavior with MAPK2 and KCTD13/CUL3 pathways alterations in two new outbred rat models for the 16p11.2 syndromes with autism spectrum disorders.

Copy number variations (CNVs) of the human 16p11.2 locus are associated with several developmental/neurocognitive syndromes. Particularly, deletion and duplication of this genetic interval are found in patients with autism spectrum disorders, intellectual disability and other psychiatric traits. The high gene density associated with the region and the strong phenotypic variability of incomplete penetrance, make the study of the 16p11.2 syndromes extremely complex. To systematically study the effect of 16p11.2 CNVs and identify candidate genes and molecular mechanisms involved in the pathophysiology, mouse models were generated previously and showed learning and memory, and to some extent social deficits. To go further in understanding the social deficits caused by 16p11.2 syndromes, we engineered deletion and duplication of the homologous region to the human 16p11.2 genetic interval in two rat outbred strains, Sprague Dawley (SD) and Long Evans (LE). The 16p11.2 rat models displayed convergent defects in social behavior and in the novel object test in male carriers from both genetic backgrounds. Interestingly major pathways affecting MAPK1 and CUL3 were found altered in the rat 16p11.2 models with additional changes in males compared to females. Altogether, the consequences of the 16p11.2 genetic region dosage on social behavior are now found in three different species: humans, mice and rats. In addition, the rat models pointed to sexual dimorphism with lower severity of phenotypes in rat females compared to male mutants. This phenomenon is also observed in humans. We are convinced that the two rat models will be key to further investigating social behavior and understanding the brain mechanisms and specific brain regions that are key to controlling social behavior.

Novel maternal duplication of 6p22.3-p25.3 with subtelomeric 6p25.3 deletion: new clinical findings and genotype–phenotype correlations

BackgroundCopy-number variants (CNVs) drive many neurodevelopmental-related disorders. Although many neurodevelopmental-related CNVs can give rise to widespread phenotypes, it is necessary to identify the major genes contributing to phenotypic presentation. Copy-number variations in chromosome 6, such as independent 6p deletion and 6p duplication, have been reported in several live-born infants and present widespread abnormalities such as intellectual disability, growth deficiency, developmental delay, and multiple dysmorphic facial features. However, a contiguous deletion and duplication in chromosome 6p regions have been reported in only a few cases.Case presentationIn this study, we reported the first duplication of chromosome band 6p25.3–p22.3 with deletion of 6p25.3 in a pedigree. This is the first case reported involving CNVs in these chromosomal regions. In this pedigree, we reported a 1-year-old boy with maternal 6p25-pter duplication characterized by chromosome karyotype. Further analysis using CNV-seq revealed a 20.88-Mb duplication at 6p25.3-p22.3 associated with a contiguous 0.66-Mb 6p25.3 deletion. Whole exome sequencing confirmed the deletion/duplication and identified no pathogenic or likely pathogenic variants related with the patient´s phenotype. The proband presented abnormal growth, developmental delay, skeletal dysplasia, hearing loss, and dysmorphic facial features. Additionally, he presented recurrent infection after birth. CNV-seq using the proband´s parental samples showed that the deletion/duplication was inherited from the proband´s mother, who exhibited a similar phenotype to the proband. When compared with other cases, this proband and his mother presented a new clinical finding: forearm bone dysplasia. The major candidate genes contributing to recurrent infection, eye development, hearing loss features, neurodevelopmental development, and congenital bone dysplasia were further discussed.ConclusionsOur results showed a new clinical finding of a contiguous deletion and duplication in chromosome 6p regions and suggested candidate genes associated with phenotypic features, such as FOXC1, SERPINB6, NRN1, TUBB2A, IRF4, and RIPK1.

Molecular Identification of Candida albicans and C. dubliniensis Using Small Subunit rRNA Gene Sequence in Kerbala, Iraq.

This study was conducted to confirm the phenotypic diagnosis of two Candida species, including Candida albicans (C. albicans) and Candida dubliniensis (C. dubliniensis). They were previously isolated in another study from cases of oral candidiasis using polymerase chain reaction and determining the nitrogenous base sequences of the 18 SrRNA product duplication using the NS1 and NS8 primers. The sequences of the multiple bases were analyzed using the Basic Local Alignment Search Tool program (BLAST), which proved that the two diagnosed Candida strains belong to two species, including C. albicans and C. dubliniensis, respectively. Additionally, the comparison of these sequences to the data available in the National Center for Biotechnology Information (NCBI) database showed that C. albicans strains in this study were 99% similar to the universal strains of C. albicans from Japan, Brazil, the United States, Germany, India, China, Pakistan, and Egypt. The C. dubliniensis strains in this study also had the highest genetic similarity rate of 99% to the C. dubliniensis strains isolated from the United States, Netherlands, France, and Germany. The study strains were recorded in the GenBank database with the sequence codes MZ574137 and MZ574410.1 for C. albicans and C. dubliniensis, respectively. The results of the 18 SrRNA region's duplication also showed variations between C. albicans and C. dubliniensis, represented by the presence of three mutations of the first type and two mutations in the second type at different sequence sites.

Molecular cytogenetic analysis using FISH and HD-oligo micro array identified an unusual novel Down syndrome caseMolecular cytogenetic analysis using FISH and HD-oligo micro array identified an unusual novel Down syndrome case

Background: Down syndrome, caused due to trisomy of chromosome 21. Methods: 131 suspected cases of DS from university hospital after obtaining written informed consent clinical history and photographs were also recorded. Diagnosis carried out by tacking peripheral blood from the children, setting up whole blood culture as well as DNA extraction from leukocytes for molecular analysis. G-banding by Saline-Trypsin-Giemsa (STG) method and Karyotyping. Results: They were into four categories using automated Karyotyper. Category 1, out of 131 96(73.28%) cases of these had trisomy 21 while Category 2, showed 3(2.29%) cases with translocation or isochromosome involving chromosome 21. Category 3, was 0 mosaics cases. Category 4, was 0, will be karyotypically 46,/XY but show partial duplications case. An unusual Down syndrome is Category 5, had remaining 32(24.42%) cases, though referred for DS were karyotypically 46,XX or 46,XY. Of these only one cases were judiciously selected and tested for partial duplication of Down syndrome critical region (DSCR) with the help of FISH by using LSI 21 chromosome 21 specific probe but as such no duplication was observed. One of the above two case was further investigated through oligo-based cytogenetic array for micro-duplication or deletion of region on chromosome 21 other than the DSCR and it revealed no duplication or deletion of any part of chromosome 21 or whole genome. Conclusion: This study suggested besides trisomy 21 and chromosomal rearrangements there might be genetic imbalances leading to perturbations of pathway/s could result unusual Down syndrome.

Changes in HRSV Epidemiology but Not Circulating Variants in Hospitalized Children due to the Emergence of SARS-CoV-2.

This study assesses the circulation of human respiratory syncytial virus (HRSV) genotypes before, during, and toward the end of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in children and determines the influence of the pandemic on HRSV circulation patterns and evolution. Phylogenetic analysis of the hypervariable glycoprotein G gene was performed on 221/261 (84.7%) HRSV-positive samples and shows two separated clusters, one belonging to HRSV-A (129/221) and another to HRSV-B (92/221). All Slovenian HRSV-A strains contained the 72-nucleotide-long duplicated region in the attachment glycoprotein G gene and were classified as lineage GA2.3.5. All Slovenian HRSV-B strains similarly contained a 60-nucleotide-long duplicated region in the attachment glycoprotein G gene and were classified as lineage GB5.0.5a. During the 3-year period (2018-2021) covered by the study, no significant differences were observed within strains detected before the SARS-CoV-2 pandemic, during it, and after the implementation of nonpharmaceutical preventive measures. Slovenian HRSV-A strains seem to be more diverse than HRSV-B strains. Therefore, further whole-genome investigations would be required for better monitoring of the long-term impact of SARS-CoV-2 endemic circulation and the formation of new HRSV lineages and epidemiological patterns.

A High Frequency of Chromosomal Duplications in Unicellular Algae Is Compensated by Translational Regulation.

Although duplications have long been recognized as a fundamental process driving major evolutionary innovations, direct estimates of spontaneous chromosome duplication rates, leading to aneuploid karyotypes, are scarce. Here, from mutation accumulation (MA) experiments, we provide the first estimates of spontaneous chromosome duplication rates in six unicellular eukaryotic species, which range from 1 × 10-4 to 1 × 10-3 per genome per generation. Although this is ∼5 to ∼60 times less frequent than spontaneous point mutations per genome, chromosome duplication events can affect 1-7% of the total genome size. In duplicated chromosomes, mRNA levels reflected gene copy numbers, but the level of translation estimated by polysome profiling revealed that dosage compensation must be occurring. In particular, one duplicated chromosome showed a 2.1-fold increase of mRNA but translation rates were decreased to 0.7-fold. Altogether, our results support previous observations of chromosome-dependent dosage compensation effects, providing evidence that compensation occurs during translation. We hypothesize that an unknown posttranscriptional mechanism modulates the translation of hundreds of transcripts from genes located on duplicated regions in eukaryotes.

Panhypopituitarism in an Adult Patient with William-Beuren Region Duplication Syndrome: A Rare Case Report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Variants detection in regions of segmental duplication facilitates molecular diagnosis for IEI such as chronic granulomatous disease caused by NCF1 mutations

With the expanding application of next-generation sequencing (NGS) in clinical practice, rapid progress has been made in molecular diagnoses for diseases such as inborn errors of immunity (IEI). However, due to characteristic short read length and fragment size for NGS, genomic regions with segmental duplication pose a big challenge for accurate mutation detection. Reads originating from segmental duplications are mapped with high ambiguity and are often discarded by most variant callers, leading to poor variant identification. Dozens of known IEI causal genes are located in regions of segmental duplications, such as NCF1, IGLL1, FCGR3A, etc. It is important to increase the sensitivity of mutation detections in such regions.In this study, we develop a strategy to significantly increase the sensitivity of identifying rare germline variants in regions of segmental duplication for IEI patients while controlling the number of false positives. By forcing multi-aligned reads from segmental duplications to map to functionally significant coding regions in the region concerned, all possible small variants are being identified. This is followed by the identification of false positives originating from intrinsic sequence differences among genomic duplications and the identification of potential common variants by matching with an in-house database.Using simulated data and real-world data from the 'Genome In a Bottle’ project, we demonstrate a significant improvement in variant detection sensitivity, ranging from 80% to 98% and 75% to 94%, respectively. This is accompanied by a limited increase in false positives that can be dealt with by downstream analysis. Applying our method to whole exome sequencing data led to the identification of the common ΔGT mutation in NCF1 in three patients with the chronic granulomatous disease, demonstrating the power of this novel approach.In summary, we developed SDrecall, a bioinformatic method that is by far the most robust open-source approach to detect rare, disease-causing variants in regions of segmental duplication. The method should apply to both IEI and other Mendelian diseases with causal mutations located in such regions and is suited to WGS, WES, and targeted sequencing data.

Searching for intralocus sexual conflicts in the three-spined stickleback (Gasterosteus aculeatus) genome.

Differences between sexes in trait fitness optima can generate intralocus sexual conflicts that have the potential to maintain genetic diversity through balancing selection. However, these differences are unlikely to be associated with strong selective coefficients and are challenging to detect. Additionally, recent studies have highlighted that duplications on sexual chromosomes can create artifactual signals of intralocus sexual conflicts. Thus, testing the relationship between intralocus sexual conflicts and balancing selection requires stringent filtering of duplicated regions, and dedicated methods to detect loci with low levels of intersex differentiation. In this study, we investigated intralocus sexual conflicts in the three-spined stickleback using whole-genome sequencing (mean coverage = 12×) of 50 females and 49 males from an anadromous population in the St. Lawrence River, Québec, Canada. After stringent filtering of duplications from the sex chromosomes, we compared three methods to detect intralocus sexual conflicts. We found only two genomic regions under potential intralocus sexual conflict that also showed signals of balancing selection. Overall, our results suggest that most intralocus sexual conflicts do not drive long-term balancing selection and are most likely transient.

Low copy repeats in the genome: from neglected to respected

DNA paralogs that have a length of at least 1 kilobase (kb) and are duplicated with a sequence identity of over 90% are classified as low copy repeats (LCRs) or segmental duplications (SDs). They constitute 6.6% of the genome and are clustering in specific genomic loci. Due to the high sequence homology between these duplicated regions, they can misalign during meiosis resulting in non-allelic homologous recombination (NAHR) and leading to structural variation such as deletions, duplications, inversions, and translocations. When such rearrangements result in a clinical phenotype, they are categorized as a genomic disorder. The presence of multiple copies of larger genomic segments offers opportunities for evolution. First, the creation of new genes in the human lineage will lead to human-specific traits and adaptation. Second, LCR variation between human populations can give rise to phenotypic variability. Hence, the rearrangement predisposition associated with LCRs should be interpreted in the context of the evolutionary advantages.