Detection Of Copy Number Variations Research Articles

Genome-Wide Detection of Copy Number Variations Associated with Miniature Features in Horses.

Copy number variations (CNVs) are crucial structural genomic variants affecting complex traits in humans and livestock animals. The current study was designed to conduct a comprehensive comparative copy number variation analysis among three breeds, Debao (DB), Baise (BS), and Warmblood (WB), with a specific focus on identifying genomic regions associated with miniature features in horses. Using whole-genome next-generation resequencing data, we identified 18,974 CNVs across 31 autosomes. Among the breeds, we found 4279 breed-specific CNV regions (CNVRs). Baise, Debao, and Warmblood displayed 2978, 986, and 895 distinct CNVRs, respectively, with 202 CNVRs shared across all three breeds. After removing duplicates, we obtained 1545 CNVRs from 26 horse genomes. Functional annotation reveals enrichment in biological functions, including antigen processing, cell metabolism, olfactory conduction, and nervous system development. Debao horses have 970 genes overlapping with CNVRs, possibly causing their small size and mountainous adaptations. We also found that the genes GHR, SOX9, and SOX11 may be responsible for the miniature features of the Debao horse by analyzing their overlapping CNVRs. Overall, this study offers valuable insights into the widespread presence of CNVs in the horse genome. The findings contribute to mapping horse CNVs and advance research on unique miniature traits observed in the Debao horse.

Low-pass whole genome sequencing is a reliable and cost-effective approach for copy number variant analysis in the clinical setting.

Next generation sequencing technology has greatly reduced the cost and time required for sequencing a genome. An approach that is rapidly being adopted as an alternative method for CNV analysis is the low-pass whole genome sequencing (LP-WGS). Here, we evaluated the performance of LP-WGSto detect copy number variants (CNVs) in clinical cytogenetics. DNA samples with known CNVs detected by chromosomal microarray analyses (CMA) were selected for comparison and used as positive controls; our panel included 44 DNA samples (12 prenatal and 32 postnatal), comprising a total of 55 chromosome imbalances. The selected cases were chosen to provide a wide range of clinically relevant CNVs, the vast majority being associated with intellectual disability or recognizable syndromes. The chromosome imbalances ranged in size from 75kb to 90.3Mb, including aneuploidies and two cases of mosaicism. All CNVs were successfully detected by LP-WGS, showing a high level of consistency and robust performance of the sequencing method. Notably, the size of chromosome imbalances detected by CMA and LP-WGS were compatible between the two different platforms, which indicates that the resolution and sensitivity of the LP-WGS approach are at least similar to those provided by CMA. Our data show the potential use of LP-WGS to detect CNVs in clinical diagnosis and confirm the method as an alternative for chromosome imbalances detection. The diagnostic effectiveness and feasibility of LP-WGS, in this technical validation study, were evidenced by a clinically representative dataset of CNVs that allowed a systematic assessment of the detection power and the accuracy of the sequencing approach. Further, since the software used in this study is commercially available, the method can easily be tested and implemented in a routine diagnostic setting.

A novel method to assess copy number variations in melanocytic neoplasms: Droplet digital PCR for precise quantitation of MYC and MYB genes.

While most melanocytic neoplasms can be classified as either benign or malignant by histopathology alone, ancillary molecular diagnostic tests can be necessary to establish the correct diagnosis in challenging cases. Currently, the detection of copy number variations (CNVs) by fluorescence in situ hybridization and chromosomal microarray (CMA) are the most popular methods, but remain expensive and inaccessible. We aim to develop a relatively inexpensive, fast, and accessible molecular assay to detect CNVs relevant to melanoma using droplet digital polymerase chain reaction (ddPCR) technology. In this proof-of-concept study, we evaluated CNVs in MYC and MYB genes from 73 cases of benign nevi, borderline melanocytic lesions, and primary and metastatic melanoma at our institution from 2015 to 2022. A multiplexed ddPCR assay and CMA were performed on each sample, and the results were compared. Concordance analysis of ddPCR with CMA for quantification of MYC and MYB CNVs revealed a sensitivity and specificity of 89% and 86% for MYC and 83% and 74% for MYB, respectively. We demonstrate the first use of a multiplexed ddPCR assay to identify CNVs in melanocytic neoplasms. With further improvement and validation, ddPCR may represent a low-cost and rapid tool to aid in the diagnosis of histopathologically ambiguous melanocytic tumors.

Comparative Benchmarking of Optical Genome Mapping and Chromosomal Microarray Reveals High Technological Concordance in CNV Identification and Additional Structural Variant Refinement.

The recommended practice for individuals suspected of a genetic etiology for disorders including unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA) involves a genetic testing workflow including chromosomal microarray (CMA), Fragile-X testing, karyotype analysis, and/or sequencing-based gene panels. Since genomic imbalances are often found to be causative, CMA is recommended as first tier testing for many indications. Optical genome mapping (OGM) is an emerging next generation cytogenomic technique that can detect not only copy number variants (CNVs), triploidy and absence of heterozygosity (AOH) like CMA, but can also define the location of duplications, and detect other structural variants (SVs), including balanced rearrangements and repeat expansions/contractions. This study compares OGM to CMA for clinically reported genomic variants, some of these samples also have structural characterization by fluorescence in situ hybridization (FISH). OGM was performed on IRB approved, de-identified specimens from 55 individuals with genomic abnormalities previously identified by CMA (61 clinically reported abnormalities). SVs identified by OGM were filtered by a control database to remove polymorphic variants and against an established gene list to prioritize clinically relevant findings before comparing with CMA and FISH results. OGM results showed 100% concordance with CMA findings for pathogenic variants and 98% concordant for all pathogenic/likely pathogenic/variants of uncertain significance (VUS), while also providing additional insight into the genomic structure of abnormalities that CMA was unable to provide. OGM demonstrates equivalent performance to CMA for CNV and AOH detection, enhanced by its ability to determine the structure of the genome. This work adds to an increasing body of evidence on the analytical validity and ability to detect clinically relevant abnormalities identified by CMA. Moreover, OGM identifies translocations, structures of duplications and complex CNVs intractable by CMA, yielding additional clinical utility.

Detection of copy number variations based on a local distance using next-generation sequencing data.

As one of the main types of structural variation in the human genome, copy number variation (CNV) plays an important role in the occurrence and development of human cancers. Next-generation sequencing (NGS) technology can provide base-level resolution, which provides favorable conditions for the accurate detection of CNVs. However, it is still a very challenging task to accurately detect CNVs from cancer samples with different purity and low sequencing coverage. Local distance-based CNV detection (LDCNV), an innovative computational approach to predict CNVs using NGS data, is proposed in this work. LDCNV calculates the average distance between each read depth (RD) and its k nearest neighbors (KNNs) to define the distance of KNNs of each RD, and the average distance between the KNNs for each RD to define their internal distance. Based on the above definitions, a local distance score is constructed using the ratio between the distance of KNNs and the internal distance of KNNs for each RD. The local distance scores are used to fit a normal distribution to evaluate the significance level of each RDS, and then use the hypothesis test method to predict the CNVs. The performance of the proposed method is verified with simulated and real data and compared with several popular methods. The experimental results show that the proposed method is superior to various other techniques. Therefore, the proposed method can be helpful for cancer diagnosis and targeted drug development.

Identification and Management of a Novel PRDM5 Gene Pathologic Variant in a Family With Brittle Cornea Syndrome.

The aim of this study was to report a novel PRDM5 pathologic variant and ophthalmic findings in a family with 3 children diagnosed with brittle cornea syndrome (BCS). Histopathologic findings and surgical outcome of a child with BCS who underwent full-thickness corneal transplant are described. This is an observational case report of a nonconsanguineous Laotian family with 3 siblings diagnosed with BCS. Data collected included visual acuity, cycloplegic refraction, slit-lamp biomicroscopy, dilated fundus examination, corneal pachymetry, corneal topography, and general medical findings. Targeted testing through PRDM5 gene sequencing with copy number variation detection was conducted. The 3 siblings included a 12-year-old boy and 8- and 6-year-old sisters, all of whom presented with myopia, blue-tinted sclerae, thin corneas, and variable corneal scarring. All 3 affected children were found to be homozygous for the PRDM5 gene variant c.1117_1123delinsTTTAATGCTTACAAATGTTTG p.Asp373Phefs*57. Coding sequences of PRDM5 and ZNF469 genes were sequenced in their entirety, and this was the only pathologic variant present in this family. The youngest affected sister developed persistent hydrops with severely decreased vision and underwent penetrating keratoplasty. Histopathology revealed severe corneal thinning, diffuse absence of Bowman layer, and ruptured Descemet membrane scrolls. Three siblings with clinical signs of BCS, including corneal thinning, myopia, and blue sclerae, were found to have a novel PRDM5 gene pathologic variant. This pathologic variant has not been previously reported, although 1 downstream nonsense pathologic variant has been reported as pathogenic. The similar phenotypes in all affected patients support the pathogenicity of this variant. Surgical management of BCS presents unique challenges due to severe tissue fragility.

Saliva DNA: An alternative biospecimen for single nucleotide polymorphism chromosomal microarray analysis in autism.

Chromosomal microarray analysis (CMA) is typically performed for investigation of autism using blood DNA. However, blood collection poses significant challenges for autistic children with repetitive behaviors and sensory and communication issues, often necessitating physical restraint or sedation. Noninvasive saliva collection offers an alternative, however, no published studies to date have evaluated saliva DNA for CMA in autism. Furthermore, previous reports suggest that saliva is suboptimal for detecting copy number variation. We therefore aimed to evaluate saliva DNA for single nucleotide polymorphism (SNP) CMA in autistic children. Saliva DNA from 48 probands and parents (n = 133) was obtained with a mean concentration of 141.7 ng/μL. SNP CMA was successful in 131/133 (98.5%) patients from which we correlated the size and accuracy of a copy number variant(s) called between a proband and carrier parent, and for a subgroup (n = 17 probands) who had a previous CMA using blood sample. There were no discordant copy number variant results between the proband and carrier parent, or the subgroup, however, there was an acceptable mean size difference of 0.009 and 0.07 Mb, respectively. Our findings demonstrate that saliva DNA can be an alternative for SNP CMA in autism, which avoids blood collection with significant implications for clinical practice guidelines.

Identification of the first homozygous intragenic deletion in the YY1AP1 gene in a consanguineous family: New insights into the phenotypic variability associated with Grange syndrome.

Grange syndrome (GRNG-MIM#135580) is a rare recessive disorder associating variable features including diffuse vascular stenosis, brachysyndactyly, osteopenia with increased bone fragility, cardiac malformations, and variable developmental delay. Since its first description in 1998, only 15 individuals from 10 families have been reported, carrying homozygous or compound heterozygous frameshift or nonsense variants in YY1AP1. In a patient with cutaneous and bone syndactyly and a hemorrhagic stroke at the age of 16 months, consistent with a clinical diagnosis of GRNG, we performed exome sequencing after negative array-CGH and congenital limb malformation panel results. Copy number variant analysis from exome data identified a homozygous intragenic out-of-frame deletion of 1.84 kb encompassing exons seven and eight of YY1AP1, confirming a molecular diagnosis of GRNG. Genetic counseling led to the identification of additional family members compatible with GRNG. Here, we provide new insights into the phenotypic variability associated with GRNG and highlight the utility of the detection of small copy number variants to identify the molecular causes of heterogeneous malformative genetic disorders.

Genetic Diagnosis of Children With Neurodevelopmental Disorders Using Whole Genome Sequencing

BackgroundNeurodevelopmental disorders (NDDs) have diverse phenotypes. Their genetic diagnoses are often challenged by difficulties of targeting causative genes due to heterogeneous genetic etiologies. The objective of this study was to perform genetic diagnosis of children with NDDs using whole genome sequencing. MethodsThis study included 78 pediatric patients with NDDs and their 152 family members for whole genome sequencing (WGS). All cases except one were families with at least two members. Seventy-five patients had previously undergone other genetic tests besides WGS. Detected variants were classified according to the guidelines of the American College of Medical Genetics and Genomics. ResultsAmong 78 probands, 26 patients were genetically diagnosed with NDDs through WGS, showing a diagnostic rate of 33.3%. Of them, 22 cases had de novo variants (DNVs) identified through trio analysis. Of these DNVs, half were novel variants. Three structural variants, including a multiexon deletion, a contiguous gene deletion involving 13 Mb, and a retrotransposon insertion, were revealed by WGS. All cases except one had defects in different genes, consistent with the phenotypically diverse nature of NDDs. In addition, three patients were inconclusive, two of them had one likely pathogenic variant in a gene associated with autosomal recessive disease and the other one had no clinical phenotypes associated with the detected DNV. ConclusionsOur experience demonstrates the advantage of WGS in the diagnosis of NDDs, including detection of copy number variations and also the advantage of trio sequencing for interpretation of DNVs.

Copy number variation analysis in 138 families with steroid-resistant nephrotic syndrome identifies causal homozygous deletions in PLCE1 and NPHS2 in two families.

Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of kidney failure in children and adults under the age of 20years. Previously, we were able to detect by exome sequencing (ES) a known monogenic cause of SRNS in 25-30% of affected families. However, ES falls short of detecting copy number variants (CNV). Therefore, we hypothesized that causal CNVs could be detected in a large SRNS cohort. We performed genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on a cohort of 138 SRNS families, in whom we previously did not identify a genetic cause through ES. We evaluated ES and CNV data for variants in 60 known SRNS genes and in 13 genes in which variants are known to cause a phenocopy of SRNS. We applied previously published, predefined criteria for CNV evaluation. We detected a novel CNV in two genes in 2 out of 138 families (1.5%). The 9,673bp homozygous deletion in PLCE1 and the 6,790bp homozygous deletion in NPHS2 were confirmed across the breakpoints by PCR and Sanger sequencing. We confirmed that CNV analysis can identify the genetic cause in SRNS families that remained unsolved after ES. Though the rate of detected CNVs is minor, CNV analysis can be used when there are no other genetic causes identified. Causative CNVs are less common in SRNS than in other monogenic kidney diseases, such as congenital anomalies of the kidneys and urinary tract, where the detection rate was 5.3%. A higher resolution version of the Graphical abstract is available as Supplementary information.

Non-invasive prenatal testing (NIPT): Combination of copy number variant and gene analyses using an "in-house" target enrichment next generation sequencing-Solution for non-centralized NIPT laboratory?

Recent studies have integrated copy number variant (CNV) and gene analysis using target enrichment. Here, we transferred this concept to our routine genetics laboratory, which is not linked to centralized non-invasive prenatal testing (NIPT) facilities. From a cohort of 100 pregnant women, 22 were selected for the analysis of maternal genomic DNA (gDNA) along with fetal cell-free DNA. Using targeted enrichment, 135 genes were analyzed, combined with aberrations of chromosomes 21, 18, 13, X, and Y. The data were subjected to specificity and sensitivity analyses, and correlated with the results from invasive testing methods. The sensitivity/specificity was determined for the CNV analysis of chromosomes: 21 (80%/75%), 18 (-/82%), 13 (100%/67%), and Y (100%/100%). The gene detection was valid for maternal gDNA. However, for cell-free fetal DNA, it was not possible to determine the boundary between an artifact and a real sequence variant. The target enrichment method combining CNV and gene detection seems feasible in a regular laboratory. However, this method can only be responsibly optimized with a sufficient number of controls and further validation on a strong bioinformatic background. The present results showed that NIPT should be performed in specialized centers, and that its introduction to isolated laboratories may not provide valid data.

A comprehensive framework for detecting copy number variants from single nucleotide polymorphism data: 'rCNV', a versatile r package for paralogue and CNV detection.

Recent studies have highlighted the significant role of copy number variants (CNVs) in phenotypic diversity, environmental adaptation and species divergence across eukaryotes. The presence of CNVs also has the potential to introduce genotyping biases, which can pose challenges to accurate population and quantitative genetic analyses. However, detecting CNVs in genomes, particularly in non-model organisms, presents a formidable challenge. To address this issue, we have developed a statistical framework and an accompanying r software package that leverage allelic-read depth from single nucleotide polymorphism (SNP) data for accurate CNV detection. Our framework capitalises on two key principles. First, it exploits the distribution of allelic-read depth ratios in heterozygotes for individual SNPs by comparing it against an expected distribution based on binomial sampling. Second, it identifies SNPs exhibiting an apparent excess of heterozygotes under Hardy-Weinberg equilibrium. By employing multiple statistical tests, our method not only enhances sensitivity to sampling effects but also effectively addresses reference biases, resulting in optimised SNP classification. Our framework is compatible with various NGS technologies (e.g. RADseq, Exome-capture). This versatility enables CNV calling from genomes of diverse complexities. To streamline the analysis process, we have implemented our framework in the user-friendly r package 'rCNV', which automates the entire workflow seamlessly. We trained our models using simulated data and validated their performance on four datasets derived from different sequencing technologies, including RADseq (Chinook salmon-Oncorhynchus tshawytscha), Rapture (American lobster-Homarus americanus), Exome-capture (Norway spruce-Picea abies) and WGS (Malaria mosquito-Anopheles gambiae).

Performance of noninvasive prenatal testing for twin pregnancies in South China

ObjectiveThe purpose of this study was to evaluate the performance of noninvasive prenatal testing (NIPT) for the detection of chromosomal aneuploidies and copy number variations (CNVs) in twin pregnancies.MethodA cohort of 2010 women with twin pregnancies was recruited. 1331 patients opted for NIPT, and 679 patients opted for expanded NIPT (NIPT-plus). All high-risk patients were advised to undergo invasive prenatal diagnosis. All participants were followed up until 6 months after birth.ResultsTwenty-two cases were predicted to have a high risk of chromosome abnormalities by NIPT, of which 14 pregnant women underwent invasive prenatal diagnosis. The 14 cases included 3 cases of trisomy 21, 1 case of trisomy 18, 1 case of trisomy 7, 2 cases of sex chromosome aneuploidies (SCAs), and 7 cases of CNVs, of which the confirmed cases numbered 2, 1, 0, 1, and 0, respectively. Twenty cases were predicted to have a high risk of chromosome abnormalities by NIPT-plus, of which 16 pregnant women underwent invasive prenatal diagnosis. The 16 cases included 1 case of trisomy 21, 1 case of trisomy 7, 7 cases of SCAs, and 7 cases of CNVs, of which were confirmed in 1, 0, 3, and 2, respectively. No false-negative result was reported during the follow-up period.ConclusionThe NIPT/NIPT-plus has excellent performance in the detection of chromosome aneuploidies in twin pregnancies. But for CNVs, the effectiveness of NIPT is poor, and the NIPT-plus have a certain detection efficiency. It is worth noting that pre- and post-genetic counseling is especially important, and the chorionicity, mode of conception, clinical indications, and fetal fraction should be considered as influencing factors.

Germline CNV Detection through Whole-Exome Sequencing (WES) Data Analysis Enhances Resolution of Rare Genetic Diseases.

Whole-Exome Sequencing (WES) has proven valuable in the characterization of underlying genetic defects in most rare diseases (RDs). Copy Number Variants (CNVs) were initially thought to escape detection. Recent technological advances enabled CNV calling from WES data with the use of accurate and highly sensitive bioinformatic tools. Amongst 920 patients referred for WES, 454 unresolved cases were further analysed using the ExomeDepth algorithm. CNVs were called, evaluated and categorized according to ACMG/ClinGen recommendations. Causative CNVs were identified in 40 patients, increasing the diagnostic yield of WES from 50.7% (466/920) to 55% (506/920). Twenty-two CNVs were available for validation and were all confirmed; of these, five were novel. Implementation of the ExomeDepth tool promoted effective identification of phenotype-relevant and/or novel CNVs. Among the advantages of calling CNVs from WES data, characterization of complex genotypes comprising both CNVs and SNVs minimizes cost and time to final diagnosis, while allowing differentiation between true or false homozygosity, as well as compound heterozygosity of variants in AR genes. The use of a specific algorithm for calling CNVs from WES data enables ancillary detection of different types of causative genetic variants, making WES a critical first-tier diagnostic test for patients with RDs.

The predictive value of noninvasive prenatal screening for copy number variations: a cohort study and a systematic meta-analysis

ABSTRACT Objective To assess the diagnostic accuracy of noninvasive prenatal screening (NIPS) in screening for copy number variations (CNVs). Methods We conducted a systematic review and meta-analysis by combining our study results with those reported in other articles. We retrospectively collected the data of pregnant women with NIPS testing in the Hangzhou Women’s Hospital from December 2019 to February 2022. Simultaneously, a systematic search of PubMed, EMBASE, and Web of Science was carried out to identify all relevant peer-reviewed publications. Statistical analysis was performed based on the random-effects model to determine a pooled estimate of the positive predictive value (PPV). Results A total of 29 studies involving 2,667 women were included for analysis. The pooled PPV of NIPS in the detection of CNVs was 32.86% (95% confidence interval [24.61–41.64]). Statistical heterogeneity was high, while no significant publication bias was found in this meta-analysis. There were insufficient data to accurately determine sensitivity and specificity, as most studies only performed confirmatory tests on high-risk women. Conclusions The PPV of NIPS in screening for CNVs was approximately 33%. Cautions should be kept in mind for the pretest guidance and subsequent after-test counseling when offering such genome-wide NIPS tests.

Copy Number Variations in Hereditary Spastic Paraplegia-Related Genes: Evaluation of an Iranian Hereditary Spastic Paraplegia Cohort and Literature Review

Introduction: In human genetic disorders, copy number variations (CNVs) are considered a considerable underlying cause. CNVs are generally detected by array-based methods but can also be discovered by read-depth analysis of whole-exome sequencing (WES) data. We performed WES-based CNV identification in a cohort of 35 Iranian families with hereditary spastic paraplegia (HSP) patients. Methods: Thirty-five patients whose routine single-nucleotide variants (SNVs) and insertion/deletion analyses from exome data were unrevealing underwent a pipeline of CNV analysis using the read-depth detection method. Subsequently, a comprehensive search about the existence of CNVs in all 84 known HSP-causing genes was carried out in all reported HSP cases, so far. Results and Discussion: CNV analysis of exome data indicated that 1 patient harbored a heterozygous deletion in exon 17 of the SPAST gene. Multiplex ligation-dependent probe amplification analysis confirmed this deletion in the proband and his affected father. Literature review demonstrated that, to date, pathogenic CNVs have been identified in 30 out of 84 HSP-causing genes (∼36%). However, CNVs in only 17 of these genes were specifically associated with the HSP phenotype. Among them, CNVs were more common in L1CAM, PLP1, SPAST, SPG7, SPG11, and REEP1 genes. The identification of the CNV in 1 of our patients suggests that WES allows the detection of both SNVs and CNVs from a single method without additional costs and execution time. However, because of intrinsic issues of WES in the detection of large rearrangements, it may not yet be exploited to replace the CNV detection methods in standard clinical practice.

Detection of Single-Nucleotide and Copy Number Defects Underlying Hyperphenylalaninemia by Next-Generation Sequencing.

Hyperphenylalaninemia (HPA) is the most common inherited amino acid metabolism disorder characterized by serious clinical manifestations, including irreversible brain damage, intellectual deficiency and epilepsy. Due to its extensive genic and allelic heterogeneity, next-generation sequencing (NGS) technology may help to identify the molecular basis of this genetic disease. Herein, we describe the development and validation of a targeted NGS (tNGS) approach for the simultaneous detection of single-nucleotide changes and copy number variations (CNVs) in genes associated with HPA (PAH, GCH1, PTS, QDPR, PCBD1, DNAJC12) or useful for its differential diagnosis (SPR). Our tNGS approach offers the possibility to detail, with a high accuracy and in a single workflow, the combined effect of a broader spectrum of genomic variants in a comprehensive view, providing a significant step forward in the development of optimized patient care and management.

Genome-wide detection of CNV regions between Anqing six-end-white and Duroc pigs

BackgroundAnqing six-end-white pig is a native breed in Anhui Province. The pigs have the disadvantages of a slow growth rate, low proportion of lean meat, and thick back fat, but feature the advantages of strong stress resistance and excellent meat quality. Duroc pig is an introduced pig breed with a fast growth rate and high proportion of lean meat. With the latter breed featuring superior growth characteristics but inferior meat quality traits, the underlying molecular mechanism that causes these phenotypic differences between Chinese and foreign pigs is still unclear.ResultsIn this study, copy number variation (CNV) detection was performed using the re-sequencing data of Anqing Six-end-white pigs and Duroc pigs, A total of 65,701 CNVs were obtained. After merging the CNVs with overlapping genomic positions, 881 CNV regions (CNVRs) were obtained. Based on the obtained CNVR information combined with their positions on the 18 chromosomes, a whole-genome map of the pig CNVs was drawn. GO analysis of the genes in the CNVRs showed that they were primarily involved in the cellular processes of proliferation, differentiation, and adhesion, and primarily involved in the biological processes of fat metabolism, reproductive traits, and immune processes.ConclusionThe difference analysis of the CNVs between the Chinese and foreign pig breeds showed that the CNV of the Anqing six-end-white pig genome was higher than that of the introduced pig breed Duroc. Six genes related to fat metabolism, reproductive performance, and stress resistance were found in genome-wide CNVRs (DPF3, LEPR, MAP2K6, PPARA, TRAF6, NLRP4).

Diagnostic Effectiveness of Copy Number Variation Detection Using Multiplex Ligation-Dependent Probe Amplification in Patients with Lynch Syndrome-Related Cancer

Diagnostic Effectiveness of Copy Number Variation Detection Using Multiplex Ligation-Dependent Probe Amplification in Patients with Lynch Syndrome-Related Cancer

Detection of genome-wide copy number variation in Murrah buffaloes

Riverine Buffaloes, especially the Murrah breed because of their adaptability to harsh climatic conditions, is farmed in many countries to convert low-quality feed into valuable dairy products and meat. Here, we investigated the copy number variations (CNVs) in 296 Murrah buffalo using the Axiom® Buffalo Genotyping Array 90K (Affymetrix, Santa Clara, CA, USA). The CNVs were detected on the autosomes, using the Copy Number Analysis Module (CNAM) using the univariate analysis. 7937 CNVs were detected in 279 Buffaloes, the average length of the CNVs was 119,048.87 bp that ranged between 7800 and 4,561,030 bp. These CNVs were accounting for 10.33% of the buffalo genome, which was comparable to cattle, sheep, and goat CNV analyses. Further, CNVs were merged and 1541 CNVRs were detected using the Bedtools-mergeBed command. 485 genes were annotated within 196 CNVRs that were identified in at least 10 animals of Murrah population. Out of these, 40 CNVRs contained 59 different genes that were associated with 69 different traits. Overall, the study identified a significant number of CNVs and CNVRs in the Murrah breed of buffalo, with a wide range of lengths and frequencies across the autosomes. The identified CNVRs contained genes associated with important traits related to production and reproduction, making them potentially important targets for future breeding and genetic improvement efforts.