One Hundred Years of Gene Balance: How Stoichiometric Issues Affect Gene Expression, Genome Evolution, and Quantitative Traits

A century ago experiments with the flowering plant <i>Datura stramonium</i> and the fruit fly <i>Drosophila melanogaster</i> revealed that adding an extra chromosome to a karyotype was much more detrimental than adding a whole set of chromosomes. This phenomenon was referred to as gene balance and has been recapitulated across eukaryotic species. Here, we retrace some developments in this field. Molecular studies suggest that the basis of balance involves stoichiometric relationships of multi-component interactions. This concept has implication for the mechanisms controlling gene expression, genome evolution, sex chromosome evolution/dosage compensation, speciation mechanisms, and the underlying genetics of quantitative traits.

Ten Reasons Why People With Down Syndrome are Protected From the Development of Most Solid Tumors -A Review

People with Down syndrome have unique characteristics as a result of the presence of an extra chromosome 21. Regarding cancer, they present a unique pattern of tumors, which has not been fully explained to date. Globally, people with Down syndrome have a similar lifetime risk of developing cancer compared to the general population. However, they have a very increased risk of developing certain tumors (e.g., acute leukemia, germ cell tumors, testicular tumors and retinoblastoma) and, on the contrary, there are some other tumors which appear only exceptionally in this syndrome (e.g., breast cancer, prostate cancer, medulloblastoma, neuroblastoma and Wilms tumor). Various hypotheses have been developed to explain this situation. The genetic imbalance secondary to the presence of an extra chromosome 21 has molecular consequences at several levels, not only in chromosome 21 but also throughout the genome. In this review, we discuss the different proposed mechanisms that protect individuals with trisomy 21 from developing solid tumors: genetic dosage effect, tumor suppressor genes overexpression, disturbed metabolism, impaired neurogenesis and angiogenesis, increased apoptosis, immune system dysregulation, epigenetic aberrations and the effect of different microRNAs, among others. More research into the molecular pathways involved in this unique pattern of malignancies is still needed.

Mouse models of aneuploidy to understand chromosome disorders

An organism or cell carrying a number of chromosomes that is not a multiple of the haploid count is in a state of aneuploidy. This condition results in significant changes in the level of expression of genes that are gained or lost from the aneuploid chromosome(s) and most cases in humans are not compatible with life. However, a few aneuploidies can lead to live births, typically associated with deleterious phenotypes. We do not understand why phenotypes arise from aneuploid syndromes in humans. Animal models have the potential to provide great insight, but less than a handful of mouse models of aneuploidy have been made, and no ideal system exists in which to study the effects of aneuploidy per se versus those of raised gene dosage. Here, we give an overview of human aneuploid syndromes, the effects on physiology of having an altered number of chromosomes and we present the currently available mouse models of aneuploidy, focusing on models of trisomy 21 (which causes Down syndrome) because this is the most common, and therefore, the most studied autosomal aneuploidy. Finally, we discuss the potential role of carrying an extra chromosome on aneuploid phenotypes, independent of changes in gene dosage, and methods by which this could be investigated further.

A rare familial rearrangement of chromosomes 9 and 15 associated with intellectual disability: a clinical and molecular study

Background There are many reports on rearrangements occurring separately in the regions of chromosomes 9p and 15q affected in the case under study. 15q duplication syndrome is caused by the presence of at least one extra maternally derived copy of the Prader–Willi/Angelman critical region. Trisomy 9p is the fourth most frequent chromosome anomaly with a clinically recognizable syndrome often accompanied by intellectual disability. Here we report a new case of a patient with maternally derived unique complex sSMC resulting in partial trisomy of both chromosomes 9 and 15 associated with intellectual disability. Case presentation We characterise a supernumerary derivative chromosome 15: 47,XY,+der(15)t(9;15)(p21.2;q13.2), likely resulting from 3:1 malsegregation during maternal gametogenesis. Chromosomal analysis showed that a phenotypically normal mother is a carrier of balanced translocation t(9;15)(p21.1;q13.2). Her 7-year-old son showed signs of intellectual disability and a number of physical abnormalities including bilateral cryptorchidism and congenital megaureter. The child’s magnetic resonance imaging showed changes in brain volume and in structural and functional connectivity revealing phenotypic changes caused by the presence of the extra chromosome material, whereas the mother’s brain MRI was normal. Sequence analyses of the microdissected der(15) chromosome detected two breakpoint regions: HSA9:25,928,021-26,157,441 (9p21.2 band) and HSA15:30,552,104-30,765,905 (15q13.2 band). The breakpoint region on chromosome HSA9 is poor in genetic features with several areas of high homology with the breakpoint region on chromosome 15. The breakpoint region on HSA15 is located in the area of a large segmental duplication. Conclusions We discuss the case of these phenotypic and brain MRI features in light of reported signatures for 9p partial trisomy and 15 duplication syndromes and analyze how the genomic characteristics of the found breakpoint regions have contributed to the origin of the derivative chromosome. We recommend MRI for all patients with a developmental delay, especially in cases with identified rearrangements, to accumulate more information on brain phenotypes related to chromosomal syndromes.

Evaluation of the main oral manifestations associated with Down Syndrome: Integrative review

Down Syndrome or Trisomy of chromosome 21, as it is also known worldwide, is characterized by an error in chromosome distribution with the presence of an extra chromosome in the distal portion of it, generating specific physical and clinical characteristics throughout these people's lives. This paper aims to identify and discuss the main issues related to the role of oral health in the quality of life of people with Down syndrome. A search for papers was carried out in the following electronic databases: BIREME and PubMed, between the years 2010 to 2020. The search for electronic databases retrieved 22 articles. After reading the title and abstract, reading in full and applying the inclusion and exclusion criteria, a total of 09 articles were selected. It is concluded that there are frequent oral alterations in people with Down syndrome and some of these can be observed and treated from the first months of the child's life. In this way, the present study contributes in a scientific way to the general knowledge of oral problems and frequent alterations in people with down syndrome and elucidates their means of prevention and dental treatments from early childhood as a way to improve the quality of life and well-being of these patients.

Identification of Chromosome 17 Trisomy in a Cynomolgus Monkey (Macaca fascicularis) by Multicolor FISH Techniques

A female cynomolgus monkey (<i>Macaca fascicularis</i>) with facial features characteristic of Down syndrome showed abnormal behavior, unwariness toward humans, and poor concentration. The number of metaphase chromosomes in blood lymphocytes was examined and found to be 43, which indicated one extra chromosome to the normal diploid number (2n = 42). We then used Q-banding and multicolor FISH techniques to identify the extra chromosome. The results revealed an additional chromosome 17, with no other chromosomal rearrangements, such as translocations. Since no mosaicism or heterozygous variant chromosomes were observed, full trisomy 17 was assessed in this female cynomolgus monkey. Chromosome 17 corresponds to human chromosome 13, and human trisomy 13, known as Patau syndrome, results in severe clinical signs and, often, a short life span; however, this individual has reached an age of 10 years with only mild clinical signs. Although genomic differences exist between human and macaques, this individual’s case could help to reveal the pathological and genetic mechanisms of Patau syndrome.

Illumination on the structure and characteristics of Entamoeba histolytica genome.

Entamoeba histolytica, likes other Organismes, is characterized by diversity and heterogeneity in its genetic content, which is one of the most paramount reasons for survival, and the increase in susceptibility to infection. Non-condensation of chromosomes during the process of cell division and the ambiguity of the chromosomal ploidy makes predicting the exact chromosomal numeral difficult. Genes distributed across 14 chromosomes as well as many extra-chromosome elements. Most Genes compose of one axon only, with Introns in 25% of Genes. This genome is characterized by the presence of Polymorphic internal repeat regions, and several gene families, one of these large families encoding Transmembrane kinas, Cysteine protease (CP), SREHP protein, and others.

Congenital Chylothorax in Newborn with Trisomy 21

Dawn syndrome Trisomy 21 means there’s an extra copy of chromosome 21 in every cell. This is the most common form of Down syndrome, there is three types of Down syndrome. Trisomy 21 which there is an extra copy of chromosome 21 in every cell. Mosaicism occurs when a child is born with an extra chromosome in some but not all of their cells. Translocation in this type of Down syndrome, children have only an extra part of chromosome 21. There are 46 total chromosomes. However, one of them has an extra piece of chromosome 21 attached. Down syndrome is associated with a lots of complication like congenital heart disease. Vision. Hearing behavior and mental problem. Our case is Down syndrome with congenital chylothorax which is rare complication. Neonatal chylothorax results from the accumulation of chyle in the pleural space and may be either congenital or an acquired condition. Congenital chylothorax is most likely due to abnormal development or obstruction of the lymphatic system. It is often associated with hydrops fetalis. It can be idiopathic or may be associated with various chromosomal anomalies including Trisomy 21, Turner syndrome, Noonan syndrome, and other genetic abnormalities [1]. Treatment of chylothorax is multidisplenery need insertion of chest tube to decrease respiratory distress, diet management and pediatric surgery.

What Causes Down Syndrome?

Trisomy 21 (Down Syndrome) is the model human phenotype for all genome gain-dosage imbalance situations, including microduplications. Years after the sequencing of chromosome 21, the discovery of functional genomics and the creation of multiple cellular and mouse models provided an unprecedented opportunity to demonstrate the molecular consequences of genome dosage imbalance. It was stated years ago that Down syndrome, caused by meiotic separation of chromosome 21 in humans, is associated with advanced maternal age, but defining and understanding other risk factors is insufficient. Commonly referred to as Down syndrome (DS) in humans, trisomy 21 is the most cited genetic cause of mental retardation. In about 95% of cases, the extra chromosome occurs as a result of meiotic non- nondisjunction (NDJ) or abnormal separation of chromosomes. In most of these cases the error occurs during maternal oogenesis, especially in meiosis I.

Illumination on the Structure and Characteristics of Entamoeba Histolytica Genome

Entamoeba histolytica, like other Organismes, is characterized by diversity and heterogeneity in its genetic content, which is one of the most important reasons for survival, and the increase in susceptibility to infection.Non-condensation of chromosomes during the process of cell division and the ambiguity of the chromosomal ploidy makes predicting the exact chromosomal number difficult. Genes distributed across 14 chromosomes as well as many extra-chromosome elements. Most Genes composed of one axon only, with Introns in 25% of Genes. This genome is characterized by the presence of Polymorphic internal repeat regions, and several gene families, one of these large families encoding Transmembrane kinas, Cysteine protease (CP), SREHP protein, and others.