Analysis of the genomic expression profile in trisomy 18: insight into possible genes involved in the associated phenotypes

2019 ◽  
Vol 29 (2) ◽  
pp. 238-247
Author(s):  
Igor Albizua ◽  
Pankaj Chopra ◽  
Stephanie L Sherman ◽  
Michael J Gambello ◽  
Stephen T Warren
Keyword(s):  
Birth Defects ◽  
Trisomy 18 ◽  
Multiple Birth ◽  
Chromosome 18 ◽  
Extra Copy ◽  
Altered Expression ◽  
Genomic Expression ◽  
Autosomal Trisomy ◽  
Edwards Syndrome ◽  
Genome Wide

Abstract Trisomy 18, sometimes called Edwards syndrome, occurs in about 1 in 6000 live births and causes multiple birth defects in affected infants. The extra copy of chromosome 18 causes the altered expression of many genes and leads to severe skeletal, cardiovascular and neurological systems malformations as well as other medical problems. Due to the low rate of survival and the massive genetic imbalance, little research has been aimed at understanding the molecular consequences of trisomy 18 or considering potential therapeutic approaches. Our research is the first study to characterize whole-genome expression in fibroblast cells obtained from two patients with trisomy 18 and two matched controls, with follow-up expression confirmation studies on six independent controls. We show a detailed analysis of the most highly dysregulated genes on chromosome 18 and those genome-wide. The identified effector genes and the dysregulated downstream pathways provide hints of possible genotype–phenotype relationships to some of the most common symptoms observed in trisomy 18. We also provide a possible explanation for the sex-specific differences in survival, a unique characteristic of trisomy 18. Our analysis of genome-wide expression data moves us closer to understanding the molecular consequences of the second most common human autosomal trisomy of infants who survive to term. These insights might also translate to the understanding of the etiology of associated birth defects and medical conditions among those with trisomy 18.

scholarly journals A Dual Gender Rare Case with 47,XY, + 18/46,XX Karyotype: Chimera or Mosaic?

2021 ◽  
Vol 11 (01) ◽  
pp. e41-e44
Author(s):  
Ravindran Ankathil ◽  
Foong Eva ◽  
Zulaikha Abu Bakar ◽  
Nazihah Mohd Yunus ◽  
Nurul Alia Nawi ◽  
...  
Keyword(s):  
Birth Weight ◽  
Blood Sample ◽  
Cell Line ◽  
Apgar Score ◽  
Cytogenetic Analysis ◽  
Rare Case ◽  
Trisomy 18 ◽  
Normal Female ◽  
Conventional Cytogenetic Analysis ◽  
Edwards Syndrome

Our objective is to report one rare case of dual gender chimerism involving abnormal male trisomy 18 and normal female karyotype. The baby was born full term with birth weight of 1.8 kg, not vigorous with light meconium stained liquor and Apgar score of 51, 85 and 910. Parents are 40 years old and mother is G6P5 + 1. The baby had clinical features of Edwards syndrome, and a blood sample was sent to Human Genome Centre, Universiti Sains Malaysia, Malaysia for cytogenetic analysis. Conventional cytogenetic analysis results showed two distinct sex discordant genetic cell lines XY and XX in 90:10 ratio. The male genetic cell line XY also showed trisomy 18 (47,XY, + 18) consistent with clinical diagnosis of male Edwards syndrome, whereas the second genetic cell line showed normal 46,XX female. The present case was reported as dual gender chimera with chi 47,XY, + 18/46,XX karyotype pattern. To the best of available knowledge, dual gender chimerism with abnormal male trisomy 18 and normal female karyotype has not been reported so far, and this case is reported for its rarity and as the first report.

scholarly journals A Genome-Wide Analysis of Pathogenesis-Related Protein-1 (PR-1) Genes from Piper nigrum Reveals Its Critical Role during Phytophthora capsici Infection

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1007
Author(s):  
Divya Kattupalli ◽  
Asha Sreenivasan ◽  
Eppurathu Vasudevan Soniya
Keyword(s):  
Phytophthora Capsici ◽  
Regulatory Elements ◽  
Piper Nigrum ◽  
Binding Motif ◽  
Altered Expression ◽  
Genome Wide ◽  
A Genome ◽  
Pathogenesis Related Protein ◽  
Pathogenesis Related

Black pepper (Piper nigrum L.) is a prominent spice that is an indispensable ingredient in cuisine and traditional medicine. Phytophthora capsici, the causative agent of footrot disease, causes a drastic constraint in P. nigrum cultivation and productivity. To counterattack various biotic and abiotic stresses, plants employ a broad array of mechanisms that includes the accumulation of pathogenesis-related (PR) proteins. Through a genome-wide survey, eleven PR-1 genes that belong to a CAP superfamily protein with a caveolin-binding motif (CBM) and a CAP-derived peptide (CAPE) were identified from P. nigrum. Despite the critical functional domains, PnPR-1 homologs differ in their signal peptide motifs and core amino acid composition in the functional protein domains. The conserved motifs of PnPR-1 proteins were identified using MEME. Most of the PnPR-1 proteins were basic in nature. Secondary and 3D structure analyses of the PnPR-1 proteins were also predicted, which may be linked to a functional role in P. nigrum. The GO and KEGG functional annotations predicted their function in the defense responses of plant-pathogen interactions. Furthermore, a transcriptome-assisted FPKM analysis revealed PnPR-1 genes mapped to the P. nigrum-P. capsici interaction pathway. An altered expression pattern was detected for PnPR-1 transcripts among which a significant upregulation was noted for basic PnPR-1 genes such as CL10113.C1 and Unigene17664. The drastic variation in the transcript levels of CL10113.C1 was further validated through qRT-PCR and it showed a significant upregulation in infected leaf samples compared with the control. A subsequent analysis revealed the structural details, phylogenetic relationships, conserved sequence motifs and critical cis-regulatory elements of PnPR-1 genes. This is the first genome-wide study that identified the role of PR-1 genes during P. nigrum-P. capsici interactions. The detailed in silico experimental analysis revealed the vital role of PnPR-1 genes in regulating the first layer of defense towards a P. capsici infection in Panniyur-1 plants.

scholarly journals Transcriptional Gene Silencing of the Autism-Associated Long Noncoding RNA MSNP1AS in Human Neural Progenitor Cells

2016 ◽  
Vol 38 (5) ◽  
pp. 375-383 ◽  
Author(s):  
Jessica J. DeWitt ◽  
Patrick M. Hecht ◽  
Nicole Grepo ◽  
Brent Wilkinson ◽  
Oleg V. Evgrafov ◽  
...  
Keyword(s):  
Immune Response ◽  
Chromatin Remodeling ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Multiple Comparisons ◽  
Neural Progenitor ◽  
Autism Spectrum ◽  
Biological Processes ◽  
Altered Expression ◽  
Genome Wide

The long noncoding RNA MSNP1AS (moesin pseudogene 1, antisense) is a functional element that was previously associated with autism spectrum disorder (ASD) with genome-wide significance. Expression of MSNP1AS was increased 12-fold in the cerebral cortex of individuals with ASD and 22-fold in individuals with a genome-wide significantly associated ASD genetic marker on chromosome 5p14.1. Overexpression of MSNP1AS in human neuronal cells caused decreased expression of moesin protein, which is involved in neuronal process stability. In this study, we hypothesize that MSNP1AS knockdown impacts global transcriptome levels. We transfected the human neural progenitor cell line SK- N-SH with constructs that caused a 50% suppression of MSNP1AS expression. After 24 h, cells were harvested for total RNA isolation. Strand-specific RNA sequencing analysis indicated altered expression of 1,352 genes, including altered expression of 318 genes following correction for multiple comparisons. Expression of the OAS2 gene was increased >150-fold, a result that was validated by quantitative PCR. Gene ontology analysis of the 318 genes with altered expression following correction for multiple comparisons indicated that upregulated genes were significantly enriched for genes involved in immune response, and downregulated genes were significantly enriched for genes involved in chromatin remodeling. These data indicate multiple transcriptional and translational functions of MSNP1AS that impact ASD-relevant biological processes. Chromatin remodeling and immune response are biological processes implicated by genes with rare mutations associated with ASD. Our data suggest that the functional elements implicated by association of common genetic variants impact the same biological processes, suggesting a possible shared common molecular pathway of ASD.

Ocular Pathology in Trisomy 18 (Edwards’ Syndrome)

1986 ◽  
Vol 192 (3) ◽  
pp. 176-178 ◽  
Author(s):  
Jacob Pe’er ◽  
John T. Braun
Keyword(s):  
Trisomy 18 ◽  
Ocular Pathology ◽  
Edwards Syndrome

scholarly journals Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia

10.1038/ng792 ◽  
2001 ◽  
Vol 30 (1) ◽  
pp. 86-91 ◽  
Author(s):  
Simon E. Fisher ◽  
Clyde Francks ◽  
Angela J. Marlow ◽  
I. Laurence MacPhie ◽  
Dianne F. Newbury ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Chromosome 18 ◽  
Genome Wide ◽  
Trait Locus

scholarly journals NUTM1-Rearranged Neoplasms: A Heterogeneous Group of Primitive Tumors with Expanding Spectrum of Histology and Molecular Alterations: An Updated Review

2021 ◽  
Vol 28 (6) ◽  
pp. 4485-4503
Author(s):  
Wenyi Luo ◽  
Todd M. Stevens ◽  
Phillip Stafford ◽  
Markku Miettinen ◽  
Zoran Gatalica ◽  
...  
Keyword(s):  
Hematologic Malignancies ◽  
Protein Product ◽  
Clinical Aspects ◽  
Chromosome 15 ◽  
Altered Expression ◽  
Molecular Alterations ◽  
Genome Wide ◽  
Bromodomain Proteins ◽  
Oncogenic Driver ◽  
Adnexal Tumors

Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update on NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.

scholarly journals Amniotic band syndrome: etiology, clinical features, diagnosis

2005 ◽  
Vol 54 (2) ◽  
pp. 79-82
Author(s):  
V. G. Vakharlovsky ◽  
А. A. Koryukov ◽  
N. V. Belyak ◽  
А. А. Shikhmagomedov
Keyword(s):  
Birth Defects ◽  
Ultrasound Examination ◽  
Fetal Surgery ◽  
Clinical Heterogeneity ◽  
Congenital Diseases ◽  
Amniotic Band ◽  
Meckel Syndrome ◽  
Amniotic Band Syndrome ◽  
Edwards Syndrome ◽  
Limb Deformities

The article presents the problem of birth defects caused by amniotic bands (AB) amniotic band syndrome (ABS). This syndrome is of multifactorial origin, the incidence of diagnosis is 7,7:10 000 newborns. ABS is characterized by clinical heterogeneity: limb deformities (occur most frequently), head and brain abnormalities, rare cases of body disorders, omphalocele, etc. Fetal surgery through laser release of AB is described. In some cases ABS should be differentiated from Meckel syndrome, Edwards syndrome and other congenital diseases as well as neural tube defects. In case of ABS diagnosis in fetus as a result of ultrasound examination of a pregnant woman consultation of physicians (obstetriciangynaecologist, medical geneticist, specialist in ultrasound prenatal diagnostics, neonatologist surgeon) including pediatric orthopedist is needed to determine proper tactics of pregnancy management. Recurrence risks for future offspring of a woman whose child (or fetus in history) has had ABS as well as for the persons with ABS do not exceed 2 %.

scholarly journals Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength

Development ◽  
2021 ◽  
Vol 148 (19) ◽  
Author(s):  
Jennifer H. Kong ◽  
Cullen B. Young ◽  
Ganesh V. Pusapati ◽  
F. Hernán Espinoza ◽  
Chandni B. Patel ◽  
...  
Keyword(s):  
Small Molecules ◽  
Birth Defects ◽  
Birth Defect ◽  
Hedgehog Signaling ◽  
Multiple Birth ◽  
In Utero Exposure ◽  
Membrane Protein Complex ◽  
Protein Target ◽  
Hh Signaling ◽  
Genetic And Environmental Factors

ABSTRACT Birth defects result from interactions between genetic and environmental factors, but the mechanisms remain poorly understood. We find that mutations and teratogens interact in predictable ways to cause birth defects by changing target cell sensitivity to Hedgehog (Hh) ligands. These interactions converge on a membrane protein complex, the MMM complex, that promotes degradation of the Hh transducer Smoothened (SMO). Deficiency of the MMM component MOSMO results in elevated SMO and increased Hh signaling, causing multiple birth defects. In utero exposure to a teratogen that directly inhibits SMO reduces the penetrance and expressivity of birth defects in Mosmo−/− embryos. Additionally, tissues that develop normally in Mosmo−/− embryos are refractory to the teratogen. Thus, changes in the abundance of the protein target of a teratogen can change birth defect outcomes by quantitative shifts in Hh signaling. Consequently, small molecules that re-calibrate signaling strength could be harnessed to rescue structural birth defects.

Abstract P252: Loss of HMGB2 Induces Chromatin Remodeling and Hypertrophic Growth in Cardiomyocytes

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Sarah Franklin ◽  
Haodong Chen ◽  
Scherise Mitchell-Jordan ◽  
Shuxun Ren ◽  
Peipei Ping ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Chromatin Remodeling ◽  
Nuclear Dna ◽  
Specific Pattern ◽  
Altered Expression ◽  
Hypertrophic Growth ◽  
Knock Down ◽  
Genome Wide ◽  
Chromatin Structural

Nuclear DNA is packaged around the octameric nucleosome core particle, constituting the basic building block of chromatin. Non-nucleosome chromatin structural molecules have been shown to induce higher order packaging of DNA into structurally compact and inactive heterochromatin, or loosely packed and active euchromatin. These chromatin remodeling events are thought to establish a cell type specific pattern of gene expression. During the development of cardiac hypertrophy and failure, genes normally only expressed during development are re-activated. While a number of transcription factors involved in these changes in fetal gene expression have been identified, the means for genome-wide structural remodeling of DNA are unknown. To identify factors controlling genomic plasticity in cardiomyocytes, we used mass spectrometry to quantify chromatin-associated proteins from cardiac nuclei during stages of hypertrophy and failure in the mouse. Adult mice were subjected to cardiac pressure overload by transverse aortic constriction. Chromatin was fractionated from cardiac nuclei and DNA-bound proteins were acid extracted and analyzed by mass spectrometry. We measured chromatin occupancy patterns for >300 proteins during distinct stages of heart failure. To explore the isoform specific roles of individual chromatin structural proteins, we used siRNA to knock-down expression of two high mobility group proteins (HMGB1 and 2) exhibiting altered expression in the hypertrophic heart. Loss of HMGB2 (but not HMGB1) induced robust hypertrophic growth in cardiomyocytes. qRT-PCR analyses demonstrated that HMGB2 is responsible for some but not all changes in the fetal gene program (ANF increased 150% and SERCA decreased 20%, whereas α- and β-MHC were unchanged). To further explore the endogenous regions of the genome under control of HMGB2 packing, we performed microarrays following HMGB2 knockdown. Hypertrophy or HMGB2 knock-down induced global chromatin remodeling conducive to gene expression, as measured by histone post-translational modifications and the ratio of core to linker histones. These studies reveal a novel role of HMGB2 to inhibit hypertrophic growth and provide insights into general principles for genome-wide chromatin remodeling.

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