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Results for “Relative copy number variation”

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PubMed1990

copia expression is variable among natural populations of Drosophila.

A survey of copia (retroviral-like element) expression in flies representing 37 populations worldwide of Drosophila melanogaster, Drosophila simulans and Drosophila mauritiana demonstrates that, although copia elements are present in all three species, copia-encoded transcripts are detectable only in D. melanogaster. Levels of copia transcripts vary nearly 100-fold among flies representing geographically diverse populations of D. melanogaster and this variation is not correlated with variability in copia copy number. Analysis of transcript levels in interpopulation hybrids demonstrates that much of this variability may be attributable to the action of trans-acting controls. The geographic and phylogenetic pattern of copia expression suggests that moderate to high levels of copia expression may be a relatively recent evolutionary acquisition. The potential evolutionary significance of these findings is discussed.

Animals↗

PubMed2004

Chromosome 1 trisomy compromises the virulence of Candida albicans.

Although increases in chromosome copy number typically have devastating developmental consequences in mammals, fungal cells such as Saccharomyces cerevisiae seem to tolerate trisomies without obvious impairment of growth. Here, we demonstrate that two commonly used laboratory strains of the yeast Candida albicans, CAI-4 and SGY-243, can carry three copies of chromosome 1. Although the trisomic strains grow well in the laboratory, Ura+ derivatives of CAI-4, carrying three copies of chromosome 1, are avirulent in the intravenously inoculated mouse model, unlike closely related strains carrying two copies of chromosome 1. Furthermore, changes in chromosome copy number occur during growth in an animal host and during growth in the presence of growth-inhibiting drugs. These results suggest that chromosome copy number variation provides a mechanism for genetic variation in this asexual organism.

Base Sequence↗

PubMed1992

Biased gene conversion, copy number, and apparent mutation rate differences within chloroplast and bacterial genomes.

We investigate the possibility that differences between synonymous substitution rates of organelle and bacterial genes differing only in copy number may be due to conversion bias. We find that the rather large observed difference in the synonymous rates between genes in the single copy and inverted-repeat regions of chloroplasts can be accounted for by a very small bias against new mutants. More generally, differences in the within-organelle fixation probability result in different apparent mutation rates as measured by the expected rate of appearance of cells homoplasmic for new mutants. Thus, differences in intracellular population parameters rather than molecular mechanisms can account for some variation in the apparent mutation rates of organelle genes, and possibly in other systems with variable numbers of gene copies. On the other hand, our analysis suggests that conversion bias is not a likely explanation for relatively low mutation rates observed near the replication origin of bacterial chromosomes.

Chloroplasts↗

PubMed2007

Gene copy number detection in animal studies.

Sensitive methods for the quantification of DNA fragments can be used to study an individual's genetic constitution for duplicated regions of the genome or to determine the relative proportion of different DNA fragments in heterogeneous samples such as pooled DNA from different individuals or in samples in which a fraction of the chromosomes carry a mutation. Here, we describe how we are using Pyrosequencing for this purpose. In Subheading 3., we describe a sensitive method that can be used to quantify the relative proportion of X- and Y-carrying sperm after sperm sorting in cattle. We also discuss our method for determining the copy numbers at a duplicated locus. This method has been applied to study genetic variation at the KIT locus in pigs, which have a major effect on coat color variation in this species.

Animals↗

PubMed2026

Unraveling the genomic blueprint of the Indian black soldier fly: From genome assembly to evolutionary insights.

The black soldier fly (BSF) (Hermetia illucens) has been renowned for its sustainable bioconversion capabilities, resulting in smart protein production with wide applications in animal feed, bioenergy, and biofertilizer. However, the genetic mechanisms underlying efficient bioconversion and productivity remain poorly understood. To advance strain-specific applications and strengthen genetic resource availability, we present the whole genome sequencing (WGS) data for an Indian isolate of black soldier fly. The assembled genome was 1.46 Gb with a scaffold N50 of 172.7 Mb, and a GC content of 42.6%. Furthermore, 64.17% of genomic sequences were masked as repeated, and 14,317 protein-coding sequences were identified. Variant analysis against the reference genome identified 34.44 million variants (∼33.25 million SNPs and ∼ 1.18 million INDELs), with the majority (99.3%) classified as MODIFIER, 0.54% as LOW impact, 0.14% as MODERATE, and only 0.003% as HIGH impact. Comparative genomic analysis with other related species revealed expansions of gene families in BSF associated with Immune effector (Antimicrobial peptides (AMPs), Lysozymes, and Peptidoglycan Recognition Protein (PGRP) and Detoxification (cytochrome P450 enzymes). Notably, AMPs in the Indian isolate showed enhanced copy number variation in defensin (27) and PGRP (40) compared to reference BSF, suggesting potential regional adaptations to pathogen exposure. Collectively, this genomic data provides an improved resource for evolutionary studies, functional genomics, and targeted genetic improvement of BSF for sustainable bioconversion applications.

Comparative genomics↗

PubMed2006

Intra- and interindividual epigenetic variation in human germ cells.

Epigenetics represents a secondary inheritance system that has been poorly investigated in human biology. The objective of this study was to perform a comprehensive analysis of DNA methylation variation between and within the germlines of normal males. First, methylated cytosines were mapped using bisulphite modification-based sequencing in the promoter regions of the following disease genes: presenilins (PSEN1 and PSEN2), breast cancer (BRCA1 and BRCA2), myotonic dystrophy (DM1), and Huntington disease (HD). Major epigenetic variation was detected within samples, since the majority of sperm cells of the same individual exhibited unique DNA methylation profiles. In the interindividual analysis, 41 of 61 pairwise comparisons revealed distinct DNA methylation profiles (P=.036 to 6.8 x 10(-14)). Second, a microarray-based epigenetic profiling of the same sperm samples was performed using a 12,198-feature CpG island microarray. The microarray analysis has identified numerous DNA methylation-variable positions in the germ cell genome. The largest degree of variation was detected within the promoter CpG islands and pericentromeric satellites among the single-copy DNA fragments and repetitive elements, respectively. A number of genes, such as EED, CTNNA2, CALM1, CDH13, and STMN2, exhibited age-related DNA methylation changes. Finally, allele-specific methylation patterns in CDH13 were detected. This study provides evidence for significant epigenetic variability in human germ cells, which warrants further research to determine whether such epigenetic patterns can be efficiently transmitted across generations and what impact inherited epigenetic individuality may have on phenotypic outcomes in health and disease.

Confounding Factors, Epidemiologic↗

PubMed1991

Semiquantitative analysis of integrated genomes of human T-lymphotropic virus type I in asymptomatic virus carriers.

A semiquantitative estimation of human T-lymphotropic virus type I (HTLV-I) integration by peripheral blood mononuclear cells (PBMC) was performed. Genomic DNA samples derived from 134 HTLV-I carriers were subjected to 40 or 60 cycles of the polymerase chain reaction to amplify the pol region of HTLV-I. The HTLV-I genome was detected by dot hybridization using a 32P-labeled oligonucleotide probe for the pol region. The radioactivity of hybridized dot membranes was then counted with an RI Imaging System (Ambis Inc, San Diego, CA) and the HTLV-I genome dose was determined by comparison with standard curve for serially diluted HTLV-I genome-positive DNA. A wide range of variation of HTLV-I genome integration was observed. When the integrated genome dose was calculated as the number of HTLV-I copies per 100 PBMC, 7 carriers (5%) had more than 10 copies, 56 (42%) had 1 to 10 copies, 46 (34%) had 0.1 to 1 copy, and 24 (18%) had less than 0.1 copy. In one sample, the HTLV-I genome was undetectable, which may indicate that the integrated genome was present at less than 0.01 copies per 100 PBMC. Age- or sex-related variations in the distribution of individuals with different HTLV-I genome were rather limited. However, carriers with a high level of the HTLV-I genome were always more than 30 years old and were predominantly male (six of seven).

Aging↗

PubMed2026

Using cancer profiles to identify synthetic lethal therapeutic targets and predictive biomarkers in cancer gene dependency data.

MOTIVATION: Large scale loss-of-function screens utilising CRISPR or siRNA can provide profound insights into the importance of individual genes for the survival of a cancer cell and can drive the identification of therapeutic targets and biomarkers, and the development of targeted drugs. However, the analysis of these data and the substantial bodies of metadata that relate to them, is technically challenging and typically requires substantial expertise in data science and computer coding. RESULTS: To facilitate the analysis of cancer gene dependency data by cancer biologists and clinical scientists, we have developed DepMine-a computational toolkit providing a powerful system for framing complex queries relating cancer gene dependency to the underlying genetic changes that occur in cancer cells. DepMine identifies synthetic lethal relationships between putative target genes and complex 'cancer profiles' built from user-specified combinations of mutations, copy-number variation, and expression levels, and can refine these to optimal biomarker definitions for target dependency. AVAILABILITY: The Python implementation of DepMine and associated data files can be obtained at https://github.com/UOSbioinformaticslab/depmine and is free to academics and Not-For-Profit organisations. The DepMine release referenced in this paper is archived as DOI: 10.5281/zenodo.19570601.

Humans↗

PubMed1998

Ribosomal RNA gene copy number and nucleolar-size polymorphisms within and among chicken lines selected for enhanced growth.

Ribosomal (r) DNA genotypes (rRNA gene copy number) and nucleolar phenotypes (nucleoli number and size) were studied in dam and sire commercial broiler pure lines from three primary breeder sources. Thirteen lines were studied to determine whether directionally selected broiler pure lines contain higher numbers of rRNA genes than a control line unselected for performance traits. Eight of the 13 lines exhibited rRNA gene copy averages between 261 and 331 copies, three lines had averages between 365 and 380, and two lines had average copy numbers equal to or greater than 450 rRNA genes. The overall source copy number average from one breeder company exhibited a value (402 rRNA genes) significantly different from the control value (300 rRNA genes). Nucleoli number and relative-size were examined in 9 of the 13 lines to establish ploidy and determine the population incidence of nucleolar size polymorphisms. All of the individuals examined for nucleolar phenotype expressed two nucleoli, indicating that gene copy number variation in those lines was generally unrelated to haploidy, aneuploidy, or polyploidy. A high frequency of individuals exhibited nucleolar size polymorphisms (line values of 57 to 87%). The results suggest that multiple nucleolus organizer region (NOR) types are segregating within and among broiler pure lines and that these NOR types contain variable numbers of rRNA genes that differ in nucleogenesis capacity.

Animals↗

PubMed2006

DNA microarray and proteomic strategies for understanding alcohol action.

This article summarizes the proceedings of a symposium presented at the 2005 annual meeting of the Research Society on Alcoholism in Santa Barbara, California. The organizer was James M. Sikela, and he and Michael F. Miles were chairs. The presentations were (1) Genomewide Surveys of Gene Copy Number Variation in Human and Mouse: Implications for the Genetics of Alcohol Action, by James M. Sikela; (2) Regional Differences in the Regulation of Brain Gene Expression: Relevance to the Detection of Genes Associated with Alcohol-Related Traits, by Robert Hitzemann; (3) Identification of Ethanol Quantitative Trait Loci Candidate Genes by Expression Profiling in Inbred Long Sleep/Inbred Short Sleep Congenic Mice, by Robnet T. Kerns; and (4) Quantitative Proteomic Analysis of AC7-Modified Mice, by Kathleen J. Grant.

Alcoholism↗

PubMed2006

Biological characteristics in bladder cancer depend on the type of genetic instability.

PURPOSE: Malignant tumors show an inherent genetic instability that can be classified as microsatellite instability (MSI) or chromosomal instability (CIN). To elucidate the differences in biological characteristics of bladder cancer between the two types of genetic instability, the expression of the mismatch repair (MMR) proteins, Aurora-A and p53 proteins, the number of centrosomes, numerical aberrations of chromosomes and 20q13, and DNA ploidy were examined in 100 human urothelial carcinomas of the bladder. EXPERIMENTAL DESIGN: Expressions of the MLH1, MSH2, Aurora-A, and p53 proteins and the numbers of centrosomes were immunohistochemically assessed. Numerical aberrations of chromosomes 7, 9, 17, and 20q13 spots were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed by laser scanning cytometry. RESULTS: The expression levels of the MMR related-proteins decreased in 9 of 100 tumors. Tumors with low MLH1 or MSH2 expression (designated as MSI cancers) were not linked with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, 20q13 gain, DNA aneuploidy, and disease progression. MSI cancers showed a favorable prognosis. CIN cancers (49 cases), defined as tumors with a large intercellular variation in centromere copy numbers, were associated more frequently with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, and 20q13 gain than the others (51 cases). Tumors with disease progression were included in the CIN cancer group. CONCLUSIONS: The present observations suggest that there are differences in the biological characteristics of the two types of genetic instability.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.

Autosomal recessive spinal muscular atrophy (SMA) is classified, on the basis of age at onset and severity, into three types: type I, severe; type II, intermediate; and type III, mild. The critical region in 5q13 contains an inverted repeat harboring several genes, including the survival motor neuron (SMN) gene, the neuronal apoptosis inhibitory protein (NAIP) gene, and the p44 gene, which encodes a transcription-factor subunit. Deletion of NAIP and p44 is observed more often in severe SMA, but there is no evidence that these genes play a role in the pathology of the disease. In > 90% of all SMA patients, exons 7 and 8 of the telomeric SMN gene (SMNtel) are not detectable, and this is also observed in some normal siblings and parents. Point mutations and gene conversions in SMNtel suggest that it plays a major role in the disease. To define a correlation between genotype and phenotype, we mapped deletions, using pulsed-field gel electrophoresis. Surprisingly, our data show that mutations in SMA types II and III, previously classed as deletions, are in fact due to gene-conversion events in which SMNtel is replaced by its centromeric counterpart, SMNcen. This results in a greater number of SMNcen copies in type II and type III patients compared with type I patients and enables a genotype/phenotype correlation to be made. We also demonstrate individual DNA-content variations of several hundred kilobases, even in a relatively isolated population from Finland. This explains why no consensus map of this region has been produced. This DNA variation may be due to a midisatellite repeat array, which would promote the observed high deletion and gene-conversion rate.

Centromere↗

PubMed2006

Overexpression of polo-like kinase 1 (PLK1) and chromosomal instability in bladder cancer.

Polo-like kinase 1 (PLK1) participates in bipolar spindle formation and entry into mitosis. Chromosomal instability (CIN) is caused by abnormalities in spindle formation and chromosome segregation. In this study, we investigated the relationship of PLK1 overexpression to CIN, and compared the PLK1 status with clinicopathological parameters in 101 human urothelial carcinomas of the urinary bladder. Expression of PLK1 and the number of centrosomes were assessed by immunohistochemistry. Numerical aberrations of chromosomes 7, 9 and 17 spots that allowed estimation of CIN were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed by laser scanning cytometry. Cancers with a large intercellular variation in centromere copy number were defined as CIN cancers. Tumors with PLK1 overexpression were associated more frequently with CIN (p < 0.0001), DNA aneuploidy (p = 0.0007) and centrosome amplification (p = 0.0013) than those without. Overexpression of PLK1 was significantly related to higher pathological grade (p = 0.0024), multiple tumors (p = 0.0241) and positive urine cytology (p = 0.0192). These data suggest that a high level expression of PLK1 confers tumor progression advantages to urothelial cancer cells, although other factors are also involved.

Adult↗

PubMed1996

Apolipoprotein(a) kringle IV repeat number predicts risk for coronary heart disease.

A high plasma concentration of lipoprotein(a) [Lp(a)] has been suggested as a risk factor for coronary heart disease (CHD), but some recent prospective studies have questioned the significance of Lp(a). Lp(a) concentrations are determined to a large extent by the hypervariable apo(a) gene locus on chromosome 6q2.7, which contains a variable number of identical tandemly arranged transcribed kringle IV type 2 repeats. The number of these repeats correlates inversely with plasma Lp(a) concentration. We analyzed whether apo(a) gene variation (kringle IV repeat number) is associated with CHD. Apo(a) genotypes were determined by pulsed-field gel electrophoresis/genomic blotting in CHD patients who had undergone angiography (n = 69) and control subjects matched for age, sex, and ethnicity (n = 69) and were related to Lp(a) concentration, apo(a) isoform in plasma, and disease status. Apo(a) alleles with a low kringle IV copy number ( < 22) and high Lp(a) concentration were significantly more frequent in the CHD group (P < .001), whereas large nonexpressed alleles were more frequent in control subjects. The odds ratio for CHD increased continuously with a decreasing number of kringle IV repeats and ranged from 0.3 in individuals with > 25 kringle IV repeats on both alleles to 4.6 in those with < 20 repeats on at least one allele. This provides direct genetic evidence that variation at the apo(a) gene locus, which determines Lp(a) levels, is also a determinant of CHD risk.

Alleles↗

PubMedDate not supplied

Giardia lamblia: identification and characterization of a variant-specific surface protein gene family.

Giardia lamblia trophozoites undergo antigenic variation by modulating the expression of variant-specific surface proteins (VSP), which are encoded by a number of small multigene families. We characterized the genomic copy of the VSP gene expressed by the cloned trophozoite line H7, derived from the isolate GS/M, in addition to a related, but nonexpressed, family member. The coding regions of the two genes encode closely related polypeptides (86% identity). However, differences in the coding region of these genes reside solely in an 873 bp segment. Only four differences were found between the 5' flanking sequences (465 bp). The proximal 205 base pairs downstream from the coding regions were identical, but thereafter the sequences diverged (37% identity over the next 391 bp). Mapping studies indicated that no other VSP gene was located within 4 kb pairs of the expressed H7 VSP gene, and transcripts from the nonexpressed gene were detected in neither GS/H7 nor heterogeneous trophozoites populations derived from this cloned line. Any mechanisms responsible for the differential expression of VSP genes must reconcile the near identity of DNA sequences that flank the coding regions of expressed and nonexpressed VSP genes.

Amino Acid Sequence↗

PubMed1997

Molecular evolution and host adaptation of Bordetella spp.: phylogenetic analysis using multilocus enzyme electrophoresis and typing with three insertion sequences.

A total of 188 Bordetella strains were characterized by the electrophoretic mobilities of 15 metabolic enzymes and the distribution and variation in positions and copy numbers of three insertion sequences (IS). The presence or absence of IS elements within certain lineages was congruent with estimates of overall genetic relationships as revealed by multilocus enzyme electrophoresis. Bordetella pertussis and ovine B. parapertussis each formed separate clusters, while human B. parapertussis was most closely related to IS1001-containing B. bronchiseptica isolates. The results of the analysis provide support for the hypothesis that the population structure of Bordetella is predominantly clonal, with relatively little effective horizontal gene flow. Only a few examples of putative recombinational exchange of an IS element were detected. Based on the results of this study, we tried to reconstruct the evolutionary history of different host-adapted lineages.

Adaptation, Biological↗

PubMed2001

Copy-number fluctuation by unequal crossing-over in the chicken avidin gene family.

The chicken avidin gene (AVD) forms a closely clustered gene family together with several avidin-related genes (AVRs). In this study, we used fluorescence in situ hybridization on extended DNA fibers (fiber-FISH) to show that the number of the AVD and AVR genes differs between individuals. Furthermore, the gene copy-number showed wide somatic variation in white blood cells of the individuals. The molecular mechanism underlying the fluctuation is most probably unequal crossing-over and/or unequal sister chromatid exchange, as judged by the Gaussian distribution of the gene counts. By definition, an increase in gene number on one locus should be accompanied by a decrease on the other locus in unequal sequence exchange. The results suggest that copy-number lability may be more common among gene families than previously thought. The chicken avidin gene family also provides an excellent model for studying the mechanisms of recombination and gene conversion.

Animals↗

PubMed1999

Abr1, a transposon-like element in the genome of the cultivated mushroom Agaricus bisporus (Lange) Imbach.

A 300-bp repetitive element was found in the genome of the white button mushroom, Agaricus bisporus, and designated Abr1. It is present in approximately 15 copies per haploid genome in the commercial strain Horst U1. Analysis of seven copies showed 89 to 97% sequence identity. The repeat has features typical of class II transposons (i.e., terminal inverted repeats, subterminal repeats, and a target site duplication of 7 bp). The latter shows a consensus sequence. When used as probe on Southern blots, Abr1 identifies relatively little variation within traditional and present-day commercial strains, indicating that most strains are identical or have a common origin. In contrast to these cultivars, high variation is found among field-collected strains. Furthermore, a remarkable difference in copy numbers of Abr1 was found between A. bisporus isolates with a secondarily homothallic life cycle and those with a heterothallic life cycle. Abr1 is a type II transposon not previously reported in basidiomycetes and appears to be useful for the identification of strains within the species A. bisporus.

Agaricus↗