Patterns of Inheritance: Mendelian and Non-Mendelian
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Although males have only one copy of an X-linked gene and females have two copies, males and females generally have equal amounts of the proteins encoded for by these genes. In the 1960s, Dr. Mary Lyon proposed a mechanism to explain this “dosage compensation.” This principle is known as X inactivation or the “Lyon” hypothesis. This hypothesis states that in females only one X chromosome in each somatic cell is active although recent evidence indicates that part of the inactive X chromosome remains active (2). The other X chromosome is inactivated and appears in interphase cells as a condensed sex chromatin or the “Barr body.” Inactivation occurs in the first week of embryonic development. The inactivation process is random with either the paternal or maternal X inactivated. Once an X chromosome is inactivated in a cell, all of the descendents of that cell will have the same inactive X. Therefore, X inactivation is randomly determined but fixed for all future cells. As a result of X inactivation, females have two populations of cells. One population has an active paternal X chromosome and the other has an active maternal X chromosome. Females are “mosaics” for the X chromosome with two populations of cells. Males are not mosaics but are “hemizygous.” They have only one X chromosome in each cell and that X remains active.
Hypogonadism, erectile dysfunction, and infertility in men
Philip E. Harris, Pierre-Marc G. Bouloux in Endocrinology in Clinical Practice, 2014
The 47,XXY karyotype in patients with Klinefelter’s syndrome results from nondysjunction during the first meiotic division in one of the parents. Nondysjunction of maternal chromosomes is the cause of the 47,XXY karyotype in two-thirds of affected men. Advanced maternal age is a risk factor for nondysjunction. The mechanism by which an extra X chromosome renders patients infertile is not known. In male germ cells, inactivation of the single X chromosome in primary spermatocytes of heterogametic males is necessary for spermatogenesis to proceed through meiosis. The necessity for X inactivation in male germ cell differentiation in heterogametic species is not clearly understood; however, inactivation of the single X may be necessary for normal sex chromosome pairing or to prevent expression of some X-linked genes that are detrimental to spermatogenesis.
Aicardi Syndrome and Klinefelter Syndrome
Dongyou Liu in Handbook of Tumor Syndromes, 2020
Skewed X-inactivation refers to the preferential, non-random inactivation of one of the two X chromosomes in females. While random X-inactivation keeps each X chromosome active in about half of cells, skewed X-inactivation keeps one X chromosome active in more than half of cells. Significant correlation is observed between skewed X inactivation and smaller gray matter volume in the left insula of the brain, which is involved in social, emotional, and mental processing.
Somewhere over the sex differences rainbow of myocardial infarction remodeling: hormones, chromosomes, inflammasome, oh my
Published in Expert Review of Proteomics, 2019
Kristine Y. DeLeon-Pennell, Merry L. Lindsey
X chromosome inactivation provides dosage compensation for X-linked genes between XX females and XY males [51]. For example, if a mother has a deleterious X mutation, the mutation is expressed in all cells of XY individuals but only half of the cells of XX individuals, making males more susceptible to X-linked mutations. Under normal conditions, a balanced gene expression between males and females is achieved due to X inactivation. However, X inactivation is not always 100% complete. In women, 15% of X chromosomal genes are overexpressed due to activation in both X chromosomes, while 3% are overexpressed in female mice [54]. Due to chromosomal differences, the use of mice may not fully recapitulate the role of the X chromosome. Spolarics et al. showed that blood neutrophils could be assessed for the X-linked protein marker glucose 6-phosphate dehydrogenase as a means to investigate female immune cell mosaicism using the unique inheritance pattern of X-linked polymorphisms [55]. Using an X-linked protein marker, cells can be separated and assessed for physiological differences linking mosaicism to changes in cellular function. Coupling this approach with a proteomics output would be a way to connect molecular to cell physiology.
Desmopressin acetate the first sublingual tablet to treat nocturia due to nocturnal polyuria
Published in Expert Review of Clinical Pharmacology, 2021
The new doses for desmopressin are gender specific, 25 μg dosage for women and 50 μg for men, striking a balance between clinical efficacy and risk [14]. As discussed previously, pharmacokinetics and dynamics of desmopressin vary between males and females, with females proving to be more sensitive to the drug [46,47]. Multiple studies have shown that increasing the dose of desmopressin from 25 μg to 50 μg in women yields no further clinical efficacy but rather increases the risk of hyponatremia when compared to men [46,51]. The physiological reasoning behind this gendered effect is not fully understood. Some theories suggest that the sex hormones affect the sensitivity of the kidney tubules to vasopressin and desmopressin [46]. Other theories suggest increased response to desmopressin in females is linked to the vasopressin receptor gene (AVPR2) located on the X chromosome. In female mammals, most genes on one X chromosome are silenced as a result of X chromosome inactivation. But some genes escape X inactivation and are expressed from both the active and inactive X chromosome. This skewed X inactivation may have resulted in higher levels of AVPR expression in females [57,58]. These theories ought to be further investigated in future research.
Housing of A350V IQSEC2 pups at 37 °C ambient temperature prevents seizures and permits the development of social vocalizations in adulthood
Published in International Journal of Hyperthermia, 2021
Reem Jada, Liron Zag, Veronika Borisov, Nina S. Levy, Shai Netser, Renad Jabarin, Shlomo Wagner, Kinneret Schragenheim-Rozales, Reut Shalgi, Andrew P. Levy
The generation of A350V IQSEC2 mice in a C57BL6/J background has previously been described [6]. All mice used in this study were generated from a cross between a female heterozygous for the A350V mutation and a wild-type IQSEC2 male resulting in half of the offspring having the mutation (hemizygous in males) and half being wild type for IQSEC2. Only male mice were used for experiments to avoid the confounding effects of X-inactivation in females. Mice were housed in a specific pathogen-free (SPF) facility with free access to water and food at 22 °C. All animals were kept on a 12-h light/12-h dark cycle, light on at 9.00pm, with ad libitum access to food and water. Behavioral experiments took place during the dark phase under dim red light. Mice were genotyped when they were 12–13 days old by polymerase chain reaction (PCR) from extracted tail DNA as previously described [6].
Related Knowledge Centers
- Genomic Imprinting
- Heterochromatin
- Placenta
- X Chromosome
- Embryo
- Gene Product
- Sex-Chromosome Dosage Compensation
- Skewed X-Inactivation
- Maternal to Zygotic Transition
- Mammalian Embryogenesis