Arm Of Chromosome Research Articles

Molecular Profile of the HepG2 Tumor Cell Line

Cell lines are widely used in scientific research due to their accessibility, stability, and functional similarity to the original cells. The HepG2 line, being the fourth most popular cell culture, is often used in toxicological and metabolic studies due to its partial retention of hepatocyte properties.In our study, the molecular portrait of the HepG2 cell culture was constructed for the first time. To build this portrait, we used previously obtained data for a single sample, including results of whole-genome sequencing (WGS), whole-genome bisulfite sequencing (WGBS), transcriptome (RNA-seq), translatome (Polysome-seq), and proteome (LC-MS/MS) profiling. For the assessment of HepG2 cell line heterogeneity, we analyzed whole-genome and transcriptome data published in the NCBI SRA database, as well as proteome research results available in the PRIDE resource.Our study showed that the HepG2 cell line generally demonstrates a high degree of stability at the genomic and transcriptomic levels; however, samples from China require closer attention when transferring the results of transcriptomic and proteomic experiments. The HepG2 genotype is characterized by stable chromosomal rearrangements, such as translocation between the short arms of chromosomes 1p and 21p, tetrasomy of chromosome 20, loss of the short arm of all SAT chromosomes, and the long arm of the Y chromosome. Despite the absence of 1216 protein-coding genes at the genomic level, 12,602 genes are expressed at the transcriptomic level, of which only 10,461 are detected at the translatome level, and only 1027 genes are identified at the proteome level, which is related to the limitations of mass spectrometry sensitivity. As a result of the omics data analysis, we presented a detailed molecular portrait of the HepG2 cell culture, illustrating the omics profile at various levels for each gene.

Are the chromosomal fusions that shaped the karyotype of Tetranematichthys wallacei (Siluriformes: Auchenipteridae) a shared feature among Ageneiosini species?

Abstract The genus Tetranematichthys has only three species, and none of them have undergone cytogenetic analyses. Therefore, this study brings for the first time the analysis of Tetranematichthys wallacei, collected from the Igarapé Apaú, Guamá River basin, municipality of Castanhal, Pará State, Brazil. The diploid number found was 52 chromosomes (32m+18sm+2st, NF = 104), in both sexes, with predominantly terminal and some interstitial heterochromatin. Telomeric sequences were observed exclusively in terminal regions. The 18S rDNA sites were found on pair 17sm of all specimens and in only one of the homologous of pair 7 in three specimens. The 5S rDNA sites were found in pairs 8m and 10m. Tetranematichthys wallacei exhibits characteristics worthy of attention regarding its current phylogenetic position, including a probable diploid number reduction. Additionally, it shares with Tympanopleura atronasus the 18S rDNA allocated in the long arm of a large sm chromosome (first pair) but does not share with Ageneiosus the large first m pair with evidence of fusion, as observed in Ageneiosus inermis. The chromosomal data generated for T. wallacei, along with the data from the other two previously studied Ageneiosini taxa, reinforces proposals from morphology-based studies suggesting that the tribe represents the most distinct clade within the family.

Clinicohistopathological Features and Immunohistochemical Expression Patterns of p53 in Epithelial Ovarian Tumours: A Cross-sectional Study

Introduction: Ovarian tumours represent 3% of female malignancies, with epithelial tumours constituting more than 90% of all ovarian cancers. Tumour suppressor gene 53 (TP53) mutations play an important role in the prognosis and treatment of ovarian cancer. The tumour suppressor gene Tumour Protein 53 (p53), located on the short arm of chromosome 17, acts by suppressing abnormal cell growth at the beginning of the Synthesis phase (S-phase) of the cell cycle. Previous studies have shown a correlation between p53 mutation or overexpression and patient prognosis in various types of tumours, including breast cancer, rectal cancer, intestinal cancer, lung cancer, and ovarian cancer. Aim: To investigate the clinicohistopathological features and immunohistochemical expression of p53 in Epithelial Ovarian Tumours (EOT). Materials and Methods: A cross-sectional study was conducted in the Department of Pathology at Hind Institute of Medical Sciences, Barabanki, Uttar Pradesh, India. The duration of the study was one year and two months, from September 2021 to November 2022. A total of 80 cases of EOT were included and histopathological diagnosis was performed, and immunohistochemical expression of p53 was evaluated in all cases. The Chi-square test was used to compare categorical data (the number of benign, borderline, and malignant EOT) and determine whether the difference in p53 expression (positive or negative) was statistically significant, using Statistical Package for the Social Sciences (SPSS) version 26.0. Results: The total of 80 cases of EOT in the present study comprised 56 (70%) benign, 5 (6.25%) borderline, and 19 (23.75%) malignant tumours. The p53 expression was statistically significant. Immunohistochemistry (IHC) for p53 showed diffuse strong positive nuclear staining (>60%) of the tumour cells in 14 cases, all of which were malignant epithelial tumours. Focally weak and patchy positive nuclear staining patterns (5%-60%) were observed in 64 cases, including 56 benign cases, four borderline cases, and four cases of malignant epithelial tumours, respectively. p53 positivity (<5% staining of tumour cells) was seen in two cases, one each of borderline and malignant epithelial tumour, respectively. Conclusion: The IHC marker p53 serves as a surrogate marker for p53 gene mutation, and its positivity is observed in serous EOT. Understanding p53 staining patterns can be used in conjunction with a panel of other antibodies to correctly classify morphologically confusing EOT. This can aid in assessing prognosis and understanding the biological behaviour of the tumour, which can be helpful in modifying the treatment plan.

Diverse modes of chromosome terminal deletion in spontaneous canavanine-resistant Schizosaccharomyces pombe mutants.

Canavanine resistance has been used to analyze mutation rates in the fission yeast Schizosaccharomyces pombe . However, the genetic basis of canavanine resistance in this organism remains incompletely understood. Here, we performed whole genome sequencing on five spontaneously arising canavanine-resistant S. pombe mutants, including the can2-1 mutant isolated in the 1970s. This analysis revealed that three mutants, including can2-1 , experienced terminal deletions of the left arm of chromosome II, leading to the loss of multiple amino acid transporter genes. Interestingly, these three mutants underwent chromosome terminal deletion through distinct mechanisms, including homology-driven translocation, homology-independent chromosome fusion, and de novo telomere addition. Our findings shed new light on the genetic basis of canavanine resistance and mechanisms underlying chromosome terminal deletions in fission yeast.

Linking Angelman and dup15q data for expanded research (LADDER) database: a model for advancing research, clinical guidance, and therapeutic development for rare conditions.

Angelman syndrome (AS) and duplication 15q (dup15q) syndrome are rare neurogenetic conditions arising from a common locus on the long arm of chromosome 15. Individuals with both conditions share some clinical features (e.g. intellectual disability, epilepsy) and often require lifelong care. Disease-modifying therapies for both conditions are emerging, resulting in a significant need for a better understanding of the natural history of both AS and dup15q. Patient advocacy groups for both conditions recognized a need for a data repository that would link data on individuals from multiple sources to expand research, increase understanding of natural history, and accelerate the development of treatments, resulting in the Linking Angelman and Dup15q Data for Expanded Research (LADDER) Database. This paper describes the development and functionality of the LADDER Database - including challenges, lessons learned, and preliminary feasibility - and how it can be used as a model for other rare conditions.

Emanuel Syndrome with a Distinctive Phenotype: A Case Report and Review with an Indian Perspective

Emanuel Syndrome (ES) is a chromosomal disorder characterised by the presence of an extra copy of chromosome 22, specifically a derivative 22 chromosome, which results from an unbalanced translocation involving chromosomes 11 and 22, due to 3:1 meiotic non disjunction. This leads to the gain of the 11q23-qter and 22pter-q11.2 regions. The syndrome is marked by developmental delay, facial dysmorphism, heart defects, genital abnormalities and renal anomalies. In most cases, one of the parents is a carrier of a balanced translocation, t(11;22). The present case is of a two-month-old male child suffering from failure to thrive and developmental delay, who was found to have a karyotype of 47,XY,+der(22)t(11;22)(q23.3;q11.2)dmat, resulting from a maternal balanced translocation, t(11;22)(q23;q11.2). Molecular cytogenetic testing confirmed the presence of partial trisomy 22q11.2 in the proband. This report presents a case of partial trisomy 22q11.2 resulting from a maternal balanced translocation between the long arms of chromosomes 11 and 22, associated with Congenital Heart Defects (CHD) and Congenital Diaphragmatic Hernia (CDH). Approximately, 11 comparable cases have been reported in the Indian population, with variations in breakpoints observed in some. However, none of these previous cases have identified CDH as a phenotypic feature, making this case particularly noteworthy

Genetic analysis and preliminary mapping by BSA-seq of the CmSR gene regulating the spotted rind trait in melon (Cucumis melo L.).

Melon (Cucumis melo L.) is an economically important horticultural crop. Spotted rind at maturity is an important appearance quality trait in melons. However, the gene controlling this trait remains unknown. In this study, the inheritance pattern of this trait was explored, and the candidate gene underlying this trait was also successfully identified. Genetic analysis showed that a single dominant gene, Cucumis melo Spotted Rind (CmSR), regulates the spotted rind trait. A preliminary genetic mapping analysis was conducted based on a BSA-seq approach. The CmAPRR2 gene was identified to be linked with the spotted rind trait and was located on the short arm of chromosome 4. It harbored two single-nucleotide mutations (chr4: 687014 G/A and chr4: 687244 C/A) in the non-spotted line 'Yellow 2', which may result in the alternative splicing of the transcript and an amino acid change in the respective protein, from proline to glutamine, respectively. Moreover, marker SNP687014-G/A was developed and co-segregated with the spotted rind trait. Therefore, it is speculated that the CmAPRR2 gene may be involved in the regulation of the spotted rind trait in melon. This study provides a theoretical foundation for further research on the gene regulatory mechanism of the rind color in melon.

The New Trends in Physiological and Pathological Actions of Ghrelin (Brain-Heart Axis) on the Heart and Cardiovascular System

Background: Ghrelin increased significantly the Left Ventriculus Eject Fraction and end-systolic volume after 30 minutes of intra-venous injection and without alterations heart rate and blood pressure. Ghrelin was discovered in 1999 as an only one 28 amino acid peptides (with octanoyl serine group) located on the short arm of chromosome 3 (position 3p25-26) having six exons, two are noncoding and four introns and encodes a 511 bp mRNA. Ghrelin is synthesized by the endocrine X/A-like cells located from the gastric fundus mucosa through the whole mucosa of the medium right vertical side of the stomach until to the 1 inch before anatomical pylorus. These cells are responsible to produced 80% of the whole ghrelin produced in the human body. Furthermore, other place of this production occurs at the hypothalamus, the pituitary, second portion of duodenum, pancreas, heart and other tissues. Bibliographic references also demonstrate the importance of ghrelin’s action in the main cardiovascular activities. Related to cardiovascular activities, ghrelin plays multitudinous beneficial and thereby help during cardiovascular diseases. Several studies demonstrated that ghrelin cause an anti-inflammatory activity by the inhibition of proinflammatory cytokines which can diminish inflammatory diseases in the heart, pericardium and specific innervations, for instance, vagus nerve and inhibited sympathetic nerves. Outcomes of this review emphasize these important actions of ghrelin. Methods: A systematic review of ghrelin activities over the heart and cardiovascular system with the inclusion of papers in review involved the physiological and physio pathological activities of ghrelin in vivo and in vitro studies. Results: Ghrelin is a natural tide with the growth hormone secretagogue (GHS) receptor (GHS-R) which cloned in 1996. The processes which generate this peptide and ghrelin-related peptides are transcriptional, translational and posttranslational. Homo and heterodimers of GHS-R and other yet unidentified receptors mediate the biological actions of acyl ghrelin and desacyl ghrelin. However, the main biological functions of ghrelin involve the secretion of growth hormone, stimulation of appetite and food intake at the hypothalamus, modulate acid secretion and motility, endocrine and exocrine pancreas secretion, blockaded insulin activity, heart functions and cardiovascular responses and other. Conclusion: One of the main occurrences in acute heart infarction is an increase activation of cardiac sympathetic nerve activity (CSNA) which is one of the causes of chronic cardiac dysfunction (CCD). Ghrelin is an effective for obtain a better cardiac function and by the suppression of renal sympathetic nerve activity which also have an important benefit to the acute myocardial infarction. Therefore, the physiological effects of ghrelin are very important to the body homeostasis even in the grave heart and cardiovascular diseases and in the immunological system.

Loss of function in NSD2 causes DNA methylation signature similar to that in Wolf-Hirschhorn syndrome

PurposeWolf-Hirschhorn syndrome (WHS), a contiguous gene syndrome caused by heterozygous deletions of the distal short arm of chromosome 4 that includes NSD2, reportedly causes specific DNA methylation signatures in peripheral blood cells. However, the genomic loci responsible for these signatures have not been elucidated. The present study aims to define the loci underlying WHS-related DNA methylation signatures and explore the role of NSD2 in these signatures. MethodsWe conducted genome-wide methylation analysis of individuals with WHS or NSD2 variants using an array method. We studied genome-edited knockin mice and induced pluripotent stem cells to explore the function of NSD2 variants. ResultsThree undiagnosed cases with NSD2 variants showed WHS-related DNA methylation signatures. In patient-derived induced pluripotent stem cells and genome-edited knockin mice, these variants cause NSD2 loss of function, respectively. The p.Pro905Leu variant caused decreased Nsd2 protein levels and altered histone H3-lysine 36 dimethylation levels similarly to what was observed in Nsd2 knockout mice. Nsd2 knockout and p.Pro905Leu knockin mice exhibited common DNA methylation changes. ConclusionThese results revealed that WHS-related DNA methylation signatures are dependent on NSD2 dysfunction and could be useful in identifying NSD2 variants of uncertain significance.

Identification of Sr67, a new gene for stem rust resistance in KU168-2 located close to the Sr13 locus in wheat

Key messageSr67 is a new stem rust resistance gene that represents a new resource for breeding stem rust resistant wheat cultivarsRe-appearance of stem rust disease, caused by the fungal pathogen Puccinia graminis f. sp. tritici (Pgt), in different parts of Europe emphasized the need to develop wheat varieties with effective resistance to local Pgt populations and exotic threats. A Kyoto University wheat (Triticum aestivum L.) accession KU168-2 was reported to carry good resistance to leaf and stem rust. To identify the genomic region associated with the KU168-2 stem rust resistance, a genetic study was conducted using a doubled haploid (DH) population from the cross RL6071 × KU168-2. The DH population was phenotyped with three Pgt races (TTKSK, TPMKC, and QTHSF) and genotyped using the Illumina 90 K wheat SNP array. Linkage mapping showed the resistance to all three Pgt races was conferred by a single stem rust resistance (Sr) gene on chromosome arm 6AL, associated with Sr13. Presently, four Sr13 resistance alleles have been reported. Sr13 allele-specific KASP and STARP markers, and sequencing markers all showed null alleles in KU168-2. KU168-2 showed a unique combination of seedling infection types for five Pgt races (TTKSK, QTHSF, RCRSF, TMRTF, and TPMKC) compared to Sr13 alleles. The phenotypic uniqueness of the stem rust resistance gene in KU168-2 and null alleles for Sr13 allele-specific markers showed the resistance was conferred by a new gene, designated Sr67. Since Sr13 is less effective in hexaploid background, Sr67 will be a good source of stem rust resistance in bread wheat breeding programs.

Frequency of cytosine methylation in the adjacent regions of soybean retrotransposon SORE-1 depends on chromosomal location.

Mobilization of transposable elements (TEs) is suppressed by epigenetic mechanisms involving cytosine methylation. However, few studies have focused on clarifying relationships between epigenetic influences of TEs on the adjacent DNA regions and time after insertion of TEs into the genome and/or their chromosomal location. Here we addressed these issues using soybean retrotransposon SORE-1. We analyzed SORE-1, inserted in exon 1 of the GmphyA2 gene, one of the newest insertions in this family so far identified. Cytosine methylation was detected in this element but was barely present in the adjacent regions. These results were correlated, respectively, with the presence and absence of the production of short interfering RNAs. Cytosine methylation profiles of 74 SORE-1 elements in the Williams 82 reference genome indicated that methylation frequency in the adjacent regions of SORE-1 was profoundly higher in pericentromeric regions than in euchromatic chromosome arms and was only weakly correlated with the length of time after insertion into the genome. Notably, the higher level of methylation in the 5' adjacent regions of SORE-1 coincided with the presence of repetitive elements in pericentromeric regions. Together, these results suggest that epigenetic influence of SORE-1 on the adjacent regions is influenced by its location on the chromosome.

A co-located QTL for seven spike architecture-related traits shows promising breeding use potential in common wheat (Triticum aestivum L.).

A co-located novel QTL for TFS, FPs, FMs, FFS, FFPs, KWS, and KWPs with potential of improving wheat yield was identified and validated. Spike-related traits, including fertile florets per spike (FFS), kernel weight per spike (KWS), total florets per spike (TFS), florets per spikelet (FPs), florets in the middle spikelet (FMs), fertile florets per spikelet (FFPs), and kernel weight per spikelet (KWPs), are key traits in improving wheat yield. In the present study, quantitative trait loci (QTL) for these traits evaluated under various environments were detected in a recombinant inbred line population (msf/Chuannong 16) mainly genotyped using the 16K SNP array. Ultimately, we identified 60 QTL, but only QFFS.sau-MC-1A for FFS was a major and stably expressed QTL. It was located on chromosome arm 1AS, where loci for TFS, FPs, FMs, FFS, FFPs, KWS, and KWPs were also simultaneously co-mapped. The effect of QFFS.sau-MC-1A was further validated in three independent segregating populations using a Kompetitive Allele-Specific PCR marker. For the co-located QTL, QFFS.sau-MC-1A, the presence of a positive allele from msf was associate with increases for all traits: + 12.29% TFS, + 10.15% FPs, + 13.97% FMs, + 17.12% FFS, + 14.75% FFPs, + 22.17% KWS, and + 19.42% KWPs. Furthermore, pleiotropy analysis showed that the positive allele at QFFS.sau-MC-1A simultaneously increased the spike length, spikelet number per spike, and thousand-kernel weight. QFFS.sau-MC-1A represents a novel QTL for marker-assisted selection with the potential for improving wheat yield. Four genes, TraesCS1A03G0012700, TraesCS1A03G0015700, TraesCS1A03G0016000, and TraesCS1A03G0016300, which may affect spike development, were predicted in the physical interval harboring QFFS.sau-MC-1A. Our results will help in further fine mapping QFFS.sau-MC-1A and be useful for improving wheat yield.

Development, identification, and utilization of wheat-tetraploid Thinopyrum elongatum 4EL translocation lines resistant to stripe rust.

The new stripe rust resistance gene Yr4EL in tetraploid Th. elongatum was identified and transferred into common wheat via 4EL translocation lines. Tetraploid Thinopyrum elongatum is a valuable genetic resource for improving the resistance of wheat to diseases such as stripe rust, powdery mildew, and Fusarium head blight. We previously reported that chromosome 4E of the 4E (4D) substitution line carries all-stage stripe rust resistance genes. To optimize the utility of these genes in wheat breeding programs, we developed translocation lines by inducing chromosomal structural changes through 60Co-γ irradiation and developing monosomic substitution lines. In total, 53 plants with different 4E chromosomal structural changes were identified. Three homozygous translocation lines (T4DS·4EL, T5AL·4EL, and T3BL·4EL) and an addition translocation line (T5DS·4EL) were confirmed by the genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), FISH-painting, and wheat 55K SNP array analyses. These four translocation lines, which contained chromosome arm 4EL, exhibited high stripe rust resistance. Thus, a resistance gene (tentatively named Yr4EL) was localized to the chromosome arm 4EL of tetraploid Th. elongatum. For the application of marker-assisted selection (MAS), 32 simple sequence repeat (SSR) markers were developed, showing specific amplification on the chromosome arm 4EL and co-segregation with Yr4EL. Furthermore, the 4DS·4EL line could be selected as a good pre-breeding line that better agronomic traits than other translocation lines. We transferred Yr4EL into three wheat cultivars SM482, CM42, and SM51, and their progenies were all resistant to stripe rust, which can be used in future wheat resistance breeding programs.

Characteristics of the karyotype of Ukrainian buffalos

The article presents the results of studying the karyotype of the Ukrainian buffalo population. With the help of routine and GTG methods of analysis of metaphase plates of chromosomes, it was established that in the studied animals the diploid chromosome set was equal to fifty chromosomes (2n=50), which consisted of 5 pairs of meta- and submetacentric and 19 pairs of acrocentric autosomes and one pair (XX) or (XY) sex chromosomes. The total number of chromosome arms (FN) was 60, which correspond to animals of the water buffalo species (Bubalus bubalis), a subspecies of the river buffalo (B. b. Bubalis). Cytogenetic control revealed wide intraspecies limits of spontaneous somatic mutagenesis: absence of constitutive chromosomal disorders; the frequency of metaphases with aneuploidy, the average value (M±m) of which was equal to 10.5±0.13%, polyploidy (M±m=0.7±0.25%), asynchronous separation of the centromeric regions of chromosomes - (M±m=5.3±2.00), chromosomal breaks (M±m=0.7±0.24%), the proportion of cells with micronuclei (M±m=2.5±0.39‰), binucleated cells (M±m=2.6±0.32‰) and mitotic index (M±m=4.8±0.65‰). It has been established that Ukrainian river buffaloes are characterized by high karyotype stability.

Major AspeMajor Aspects of Genetic Dyslipidemiascts of Genetic Dyslipidemias

This work addresses some dyslipidemias with known genetic conditioning and presents aspects related to genetic markers that have been pointed out as risk indicators of development of obstructive arterial coronary disease. Among all the anomalies related to lipid metabolism, with well-defined genetic conditioning, familial hypercholesterolemia is the one that has been most studied. The gene that informs the LDL-c receptor is located on the short arm of chromosome 19 and houses 18 exons. About 150 mutations in the LDL-c receptor gene, resulting from the replacement, addition or loss of a base (point mutation) or consequent to the loss or addition of more than one nucleotide (insertions and deletions), have already been identified. It results from mutations involving the gene that conditions the formation of Apo E. Apo E has several allelic forms, of which E3 is the most common and it is believed that the other forms (E2 and E4) have originated by mutations occurring in E3: a substitution of arginine for cysteine at position 112 of the amino acid sequence differentiates E4 from E3, and the same substitution at position 158 gives rise to E2. The identification of the type of mutation is therefore important for the genetic counseling of individuals.

SNP (A > G - rs13057211) but not GT(n) polymorphism in HMOX-1 promotor gene is associated with COVID-19 mortality

IntroductionCOVID-19 causes severe inflammatory respiratory distress syndrome. The global pandemic caused millions of cases of morbidity and mortality worldwide. Patients may present with variable symptoms including dyspnea, fever, and GIT manifestations. The HMOX-1 gene is located on the long (q) arm of chromosome 22 at position 12.3. HMOX-1 is expressed in all mammalian tissues at basal levels and is considered as a stress response enzyme. HMOX-1 has a specific polymorphic site with variable GT(n) repeats at the promotor region. Several authors evaluated the HMOX-1 GT(n) promoter polymorphism in different inflammatory conditions. We evaluated HMOX-1 promoter polymorphism in relation to serum Hemoxygenase level and inflammatory makers (CRP, Ferritin, PCT, IL-6 and D-dimer) in patients affected by SARS-COV-2 disease.Subjects and methodsNinety patients confirmed to be infected with COVID-19 were followed up till the study end point (recovery and discharge or death). HMOX-1 promotor GT(n) polymorphism was evaluated using Sanger sequencing. HMOX-1 enzyme serum level was measured by ELISA and the level of different inflammatory markers was assessed by available commercial kits.ResultsA novel Single nucleotide polymorphism (SNP) (A > G) - rs13057211 in the GT(n) region of HMOX-1 promoter gene was found in 40 (61.5%) COVID-19 patients out of the studied 65 patients. This (A > G) SNP was associated with higher mortality rate in COVID-19 as it was detected in 27 patients (75% of the patients who succumbed to the disease) (p = 0.021, Odds ratio = 3.7; 95% CI:1.29–10.56). Serum IL-6 (Interleuken-6) was positively correlated the length of Hospital Stay (LOHS) and procalcitonin (PCT); (p = 0.014, r: 0.651 and p < 0.001, r:0.997) respectively while negatively correlated with levels of HMOX-1 enzyme serum level (p = 0.013, r: -0.61). CRP correlated positively with LOHS (p = 0.021, r = 0.4), PCT (p = 0.044, r = 0.425) and age (p < 0.001, r = 0.685). Higher levels of D-Dimer and PCT were observed in patients with the long repeat. There was no significant difference between patients who recovered and those who died from COVID-19 as regards HMOX-1 level and GT(n) polymorphism.ConclusionWe report a novel SNP (A > G, rs13057211) in the GT(n) region of HMOX-1 promoter gene that was associated with mortality in COVID-19 patients, however no significant difference was found in HMOX-1 serum level or HMOX-1 (GT)n repeats within the studied groups.

Association between copy number alterations estimated using low-pass whole genome sequencing of formalin-fixed paraffin-embedded prostate tumor tissue and cancer-specific clinical parameters

Copy number alterations (CNAs) are frequently observed in early-stage prostate cancer and are associated with disease recurrence and tumor aggressiveness. Cost-effective assessment of CNAs could enhance clinical utility of CNAs. Here, we combined the cost-effectiveness of low-pass (low coverage) whole genome sequencing (LPWGS) and the routine availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue for assessing CNAs in a cohort of 187 men with early-stage localised prostate cancer. We detected well known CNAs in 8p, 8q, 13q and 16q and recurrent gains of the oncogene MYC and losses of the tumor suppressor genes NKX3-1, PTEN and RB1, indicating assay reliability. The estimated burden of CNAs was significantly associated with Gleason score, pathological T stage, surgical margin status and biochemical recurrence. Further, genomic losses or gains in specific chromosomal arms were significantly associated with worse BCR-free survival. Copy number signatures extracted from the LPWGS data showed potential for risk stratifying patients, where signatures S1 and S2 showed significant association to worse BCR-free survival compared to S3. Our study provides clinical validation of the associations between CNAs and tumor aggressiveness in an independent and representative RP cohort, while demonstrating the feasibility of performing LPWGS of FFPE tumor tissue for cost-effective assessment of CNAs.

Wolf-hirschhorn Syndrome in Malaysia

Introduction: Wolf–Hirschhorn syndrome (WHS) is rare but a well-known clinical condition due to partial deletion of the short arm of chromosome 4 (4p). It is distinguished by a distinctive facial appearance known as the “Greek warrior helmet”, impaired growth and development, intellectual incapacity and seizures. The features of WHS vary between individuals based on the size and location of the missing piece of chromosome 4. Methods: Six cases of unsuspected WHS were diagnosed from 2011 to 2020 using conventional cytogenetic and fluorescent in situ hybridization (FISH) with a WHS probe. Result: Four of them had a visible cytogenetic deletion on chromosome 4p whereas the remaining two were evaluated with fluorescent in situ hybridization (FISH) using a WHS probe. Conclusion: Conventional cytogenetic testing may yield normal findings and it does not rule out the syndrome. Targeted FISH with a WHS probe is a better option.

Small supernumerary marker chromosomes derived from human chromosome 11.

Introduction: With only 39 reported cases in the literature, carriers of a small supernumerary marker chromosome (sSMC) derived from chromosome 11 represent an extremely rare cytogenomic condition. Methods: Herein, we present a review of reported sSMC(11), add 18 previously unpublished cases, and closely review eight cases classified as 'centromere-near partial trisomy 11' and a further four suited cases from DECIPHER. Results and discussion: Based on these data, we deduced the borders of the pericentric regions associated with clinical symptoms into a range of 2.63 and 0.96Mb for chromosome 11 short (p) and long (q) arms, respectively. In addition, the minimal pericentric region of chromosome 11 without triplo-sensitive genes was narrowed to positions 47.68 and 60.52Mb (GRCh37). Furthermore, there are apparent differences in the presentation of signs and symptoms in carriers of larger sSMCs derived from chromosome 11 when the partial trisomy is derived from different chromosome arms. However, the number of informative sSMC(11) cases remains low, with overlapping presentation between p- and q-arm-imbalances. In addition, uniparental disomy (UPD) of 'normal' chromosome 11 needs to be considered in the evaluation of sSMC(11) carriers, as imprinting may be an influencing factor, although no such cases have been reported. Comprehensively, prenatal sSMC(11) cases remain a diagnostic and prognostic challenge.

The correlation between soluble human leukocyte antigen (sHLA-G) levels and +3010 polymorphism.

Human leukocyte antigen-G (HLA-G) is classified as non-classical HLA, located in the short arm of chromosome 6 and composed of seven introns and eight exons. The HLA-G gene has a lower frequency polymorphism in the coding area and higher variability at the regulatory 5'- and 3'-untranslated regions linked to HLA-G microRNA regulation. HLA-G molecule is known to have an immunomodulatory and tolerogenic features role. In 199 Saudi individuals, we examined the association between plasma soluble HLA-G (sHLA-G) levels and eight polymorphic different sites, including 14bp ins/del/+3003T-C/+3010C-G/+3027C-A/+3035C-T/+3142C-G/+3187A-G/+3196C-G single nucleotide polymorphisms (SNPs) in exon 8 in the HLA-G gene. Our results revealed higher frequency for rs17179101C (97%), rs1707T (92%) and rs9380142A (73%) alleles. Greater frequencies for the tested genotypes were observed in 3027C/C (rs17179101) (93%), 14bp (rs1704) ins/del (92%), +3003T/T (rs1707) (85%) and +3035C/T (rs17179108) (79%) SNP genotypes. Moreover, we observed a significant association of sHLA-G with +3010G/C (rs1710) SNP. In conclusion, we showed a significant association between 3010G/C (rs1710) SNP and the sHLA-G level among our sample for Saudi populations. Our findings demonstrated that specific SNP within the HLA-G gene is linked to sHLA-G molecule secretion, suggesting sHLA-G levels may be regulated genetically.