X chromosome

About: X chromosome is a research topic. Over the lifetime, 9862 publications have been published within this topic receiving 407354 citations. The topic is also known as: GO:0000805 & chrX.

Conservation of autosomal gene synteny groups in mouse and man

Abstract: WHILE genes on the X chromosome have been conserved during evolution1 little is known about the degree of conservation of autosomal synteny groups for species distantly related in evolution such as mouse and man. The mouse gene map based on sexual genetics2,3 has been expanded by analysis of interspecific somatic cell hybrids segregating mouse chromosomes, so that the genetic maps of man and mouse can be compared. The available information indicates that genes located on different arms of the same human chromosome are not syntenic in the mouse, and genes which are many map units apart (25–45 cM) in the mouse are unlikely to be syntenic in man4–6. In contrast, genes that are tightly linked (less than 1 cM apart) seem to remain syntenic during evolution5. In addition, in species closely related in evolution, such as mouse and rat,7 or man and non-human primates8, several homologous genes have been assigned to chromosomes that are apparently homologous by chromosome banding. Five genes in the mouse (Eno-1, Pgd, Pgm-2, Ak-2, Gpd-1) are syntenic9–11 and their human homologues have been assigned to human chromosome 1; all but the human homologue of Gpd-1 are regionally assigned to arm 1p (refs 4 and 12). This apparent conservation of a rather large autosomal synteny group prompted us to investigate the extent of conservation of other autosomal regions. The results have provided chromosomal assignments for seven gene loci in the mouse and evidence for synteny of four pairs of gene loci on four different human and mouse autosomes.

The X-files of inflammation: Cellular mosaicism of X-linked polymorphic genes and the female advantage in the host response to injury and infection

Abstract: Females as compared with males display better general health status, longevity, and improved clinical course after injury and infection. It is generally believed that the female advantage is associated with the effects of sex hormones. This review argues that the sex benefit of females during the host response is associated with polymorphism of X-linked genes and cellular mosaicism for X-linked parental alleles. Cells from females carry both parental X chromosomes (maternal, Xm; or paternal, Xp), whereas males carry only one (Xm). Because of dosage compensation and random X inactivation, half of the cells from females express either Xm or Xp. Therefore, females are cellular mosaics for their X-linked polymorphic genes. This cellular mosaicism in females represents a more adaptive and balanced cellular machinery that is advantageous during the innate immune response. Several genes encoding key metabolic and regulatory proteins reside on the X chromosome, including members of the apoptotic cascade, hormone homeostasis, glucose metabolic enzymes, superoxide-producing machinery, and the toll-like receptor/nuclear factor kappaB/c-Jun N-terminal kinase signaling pathway. Polymorphic forms of these X-linked proteins are likely to manifest in phenotypic differences in the mosaic cell populations in females and may contribute to sex-related differences in the host response to injury and infection. The unique inheritance pattern of X-linked polymorphisms and their potential confounding effects in clinical trials are also discussed; furthermore, we present potential biomarkers for studying mosaic cell populations of innate immunity.

Genome organization in the human sperm nucleus studied by FISH and confocal microscopy.

Abstract: The sperm nucleus has a unique chromatin structure where the DNA is highly condensed and associated with specific proteins, the protamines. It is a nondividing cell which is also transcriptionally inactive. After fusion with an oocyte, the sperm nucleus undergoes decondensation and, in the same time, starts replication and transcription. It has been suggested that somatic chromosomes during interphase are organized in territories which display a cell type and cell cycle specific distribution. The purpose of this work was to investigate whether chromosomes would also have a specific distribution in the sperm nucleus, which could be related to its inactive state, and have implications on the early stages of fertilization. In the present study, centromeric and telomeric sequences were detected by fluorescent techniques performed on human decondensed spermatozoa. Chromosome painting probes were used to detect the chromosome X and chromosome 13 on interphase sperm nuclei. The fluorescent signals were captured in 3D with a confocal microscope. For each of these chromatin structures, the volume, position, and distribution of the signals were analyzed in samples of 30 nuclei with the help of image analysis software. The centromeres appeared grouped in several foci that were randomly distributed within the sperm nucleus. The telomeres gave an approximately haploid number of small signals, evenly distributed throughout the nucleus. The chromosomes X and 13 occupied 4.7% and 3. 7% of the total nuclear volume, respectively. Interestingly, the X chromosome territory showed a preferential position in the anterior half of the volume of the nucleus, whereas chromosome 13 had a random position. This work shows a particular distribution of chromosome territories in the human sperm nucleus that could be related to mechanisms implicated in its specific functions. The analysis of more chromosomes and chromosomal structures, including the Y chromosome, would help to understand the structure of the human sperm chromatin, and its fundamental and clinical implications.

Testing association for markers on the X chromosome.

Abstract: Test statistics for association between markers on autosomal chromosomes and a disease have been extensively studied. No research has been reported on performance of such test statistics for association on the X chromosome. With 100,000 or more single-nucleotide polymorphisms (SNPs) available for genome-wide association studies, thousands of them come from the X chromosome. The X chromosome contains rich information about population history and linkage disequilibrium. To identify X-linked marker susceptibility to a disease, it is important to study properties of various statistics that can be used to test for association on the X chromosome. In this article, we compare performance of several approaches for testing association on the X chromosome, and examine how departure from Hardy-Weinberg equilibrium would affect type I error and power of these association tests using X-linked SNPs. The results are applied to the X chromosome of Klein et al. [2005], a genome-wide association study with 100K SNPs for age-related macular degeneration. We found that a SNP (rs10521496) covered by DIAPH2, known to cause premature ovarian failure (POF) in females, is associated with age-related macular degeneration. Genet. Epidemiol. 2007. Published 2007 Wiley-Liss, Inc.

Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells.

Abstract: The nuclear receptor transcription factor Dax1 is hypothesized to play a role in testicular development, although the mechanism of its action is unknown. Here, we present evidence that Dax1 plays an early essential role in fetal testis development. We hypothesize that upregulation of Sox9 expression in precursor somatic cells, a process required for their differentiation as Sertoli cells, depends on the coordinated expression of Dax1 , Sry and another gene, Tda1 . Our conclusion and model are based on the following experimental findings: (1) presence of a mutant Dax1 allele ( Dax1 -) results in complete gonadal sex reversal in C57BL/6JEi (B6) XY mice, whereas testes develop in DBA/2J (D2) and (B6×D2)F1 XY mice; (2) B6-DAX1 sex reversal is inherited as a complex trait that includes the chromosome 4 gene Tda1 ; (3) B6 Dax1 -/Y fetal gonads initiate development as ovaries, even though Sry expression is activated at the correct time and at appropriate levels; (4) upregulation of Sox9 does not occur in B6 Dax1 -/Y fetal gonads in spite of apparently normal Sry expression; and (5) overexpression of Sry in B6 Dax1 -/Y fetal gonads upregulates Sox9 and corrects testis development.