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.

A proposed path by which genes common to mammalian X and Y chromosomes evolve to become X inactivated

Abstract: Mammalian X and Y chromosomes evolved from an autosomal pair; the X retained and the Y gradually lost most ancestral genes1,2. In females, one X chromosome is silenced by X inactivation, a process that is often assumed to have evolved on a broadly regional or chromosomal basis3. Here we propose that genes or clusters common to both the X and Y chromosomes (X–Y genes) evolved independently along a multistep path, eventually acquiring dosage compensation on the X chromosome. Three genes studied here, and other extant genes, appear to be intermediates. ZFX, RPS4 and SMC were monitored for X inactivation in diverse species by assaying CpG-island methylation, which mirrors X inactivation in many eutherians. ZF evidently escaped X inactivation in proto-eutherians, which also possessed a very similar Y-linked gene; both characteristics were retained in most extant orders, but not in myomorph rodents. For RPS4, escape from X inactivation seems unique to primates. SMC escapes inactivation in primates and myomorphs but not in several other lineages. Thus, X inactivation can evolve independently for each of these genes. We propose that it is an adaptation to the decay of a homologous, Y-linked gene.

Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy

Abstract: A four generation family is described in which some men of normal intelligence have epilepsy and others have various combinations of epilepsy, learning difficulties, macrocephaly, and aggressive behaviour. As the phenotype in this family is distinct from other X linked recessive disorders linkage studies were carried out. Linkage analysis was done using X chromosome microsatellite polymorphisms to define the interval containing the causative gene. Genes from within the region were considered possible candidates and one of these, SYN1, was screened for mutations by direct DNA sequencing of amplified products. Microsatellite analysis showed that the region between MAOB (Xp11.3) and DXS1275 (Xq12) segregated with the disease. Two point linkage analysis demonstrated linkage with DXS1039, lod score 4.06 at theta = 0, and DXS991, 3.63 at theta = 0. Candidate gene analysis led to identification of a nonsense mutation in the gene encoding synapsin I that was present in all affected family members and female carriers and was not present in 287 control chromosomes. Synapsin I is a synaptic vesicle associated protein involved in the regulation of synaptogenesis and neurotransmitter release. The SYN1 nonsense mutation that was identified is the likely cause of the phenotype in this family.

Dosage compensation of the sex chromosomes

Abstract: Differentiated sex chromosomes evolved because of suppressed recombination once sex became genetically controlled In XX/XY and ZZ/ZW systems, the heterogametic sex became partially aneuploid after degeneration of the Y or W Often, aneuploidy causes abnormal levels of gene expression throughout the entire genome Dosage compensation mechanisms evolved to restore balanced expression of the genome These mechanisms include upregulation of the heterogametic chromosome as well as repression in the homogametic sex Remarkably, strategies for dosage compensation differ between species In organisms where more is known about molecular mechanisms of dosage compensation, specific protein complexes containing noncoding RNAs are targeted to the X chromosome In addition, the dosage-regulated chromosome often occupies a specific nuclear compartment Some genes escape dosage compensation, potentially resulting in sex-specific differences in gene expression This review focuses on dosage compensation in mammals, with comparisons to fruit flies, nematodes, and birds

Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas

Abstract: The (X;1)(p11;q21) translocation is a recurrent chromosomal abnormality in a subset of human papillary renal cell carcinomas, and is sometimes the sole cytogenetic abnormality present. Via positional cloning, we were able to identify the genes involved. The translocation results in a fusion of the transcription factor TFE3 gene on the X chromosome to a novel gene, designated PRCC, on chromosome 1. Through this fusion, reciprocal translocation products are formed, which are both expressed in papillary renal cell carcinomas. PRCC is ubiquitously expressed in normal adult and fetal tissues and encodes a putative protein of 491 aa with a relatively high content of prolines. No relevant homologies with known sequences at either the DNA or the protein level were found.