Abstract:
:A long-standing question concerning X-chromosome inactivation (XCI) has been how some genes avoid the otherwise stable chromosome-wide heterochromatinization of the inactive X chromosome. As 20% or more of human X-linked genes escape from inactivation, such genes are an important contributor to sex differences in gene expression. Although both human and mouse have genes that escape from XCI, more genes escape in humans than mice, with human escape genes often clustering in larger domains than the single escape genes of mouse. Mouse models offer a well-characterized and readily manipulated system in which to study XCI, but given the differences in genes that escape it is unclear whether the mechanism of escape gene regulation is conserved. To address conservation of the process and the potential to identify elements by modelling human escape gene regulation using mouse, we integrated a human and a mouse BAC each containing an escape gene and flanking subject genes at the mouse X-linked Hprt gene. Escape-level expression and corresponding low promoter DNA methylation of human genes RPS4X and CITED1 demonstrated that the mouse system is capable of recognizing human elements and therefore can be used as a model for further refinement of critical elements necessary for escape from XCI in humans.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Peeters SB,Korecki AJ,Simpson EM,Brown CJdoi
10.1093/hmg/ddy039subject
Has Abstractpub_date
2018-04-01 00:00:00pages
1252-1262issue
7eissn
0964-6906issn
1460-2083pii
4833562journal_volume
27pub_type
杂志文章abstract::Polyglutamine (polyQ) diseases are a growing class of inherited neurodegenerative diseases including Huntington's disease, which are caused by abnormal expansions of the polyQ stretch in each unrelated disease protein. The expanded polyQ stretch is thought to confer toxic properties on the disease proteins through alt...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg144
更新日期:2003-06-01 00:00:00
abstract::TMEM70, a 21-kDa protein localized in the inner mitochondrial membrane, has been shown to facilitate the biogenesis of mammalian F1Fo ATP synthase. Mutations of the TMEM70 gene represent the most frequent cause of isolated ATP synthase deficiency resulting in a severe mitochondrial disease presenting as neonatal encep...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw295
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg308
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abstract::Filamin B (FLNB) is a cytoplasmic protein that regulates the cytoskeletal network by cross-linking actin, linking cell membrane to the cytoskeleton and regulating intracellular signaling pathways responsible for skeletal development (Stossel, T.P., Condeelis, J., Cooley, L., Hartwig, J.H., Noegel, A., Schleicher, M. a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm114
更新日期:2007-07-15 00:00:00
abstract::Expansion of a polyglutamine tract in ataxin-3 (AT3) results in spinocerebellar ataxia type 3/Machado-Joseph disease, one of the nine polyglutamine neurodegenerative diseases. Understanding the normal functions of AT3 as well as its function in the context of expansion of the polyglutamine tract is critical for unders...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl164
更新日期:2006-08-15 00:00:00
abstract::BCS1L encodes a homolog of the Saccharomyces cerevisiae bcs1 protein, which has a known role in the assembly of Complex III of the mitochondrial respiratory chain. Phenotypes reported in association with pathogenic BCS1L variants include growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz202
更新日期:2019-11-15 00:00:00
abstract::Immunoglobulin-like domain containing receptor 1 (ILDR1) is a poorly characterized gene that was first identified in lymphoma cells. Recently, ILDR1 has been found to be responsible for autosomal recessive hearing impairment DFNB42. Patients with ILDR1 mutations cause bilateral non-progressive moderate-to-profound sen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu340
更新日期:2014-12-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp266
更新日期:2009-09-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv286
更新日期:2015-10-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi156
更新日期:2005-06-01 00:00:00
abstract::Chromosomal aneuploidy, the gain or loss of whole chromosomes, is a hallmark of pathological conditions and a causal factor of birth defects and cancer. A number of studies indicate that aneuploid cells are present at a high frequency in the brain of mice and humans, suggesting that mosaic aneuploidies are compatible ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds375
更新日期:2012-12-15 00:00:00
abstract::Understanding the role of the epigenome in protein-misfolding diseases remains a challenge in light of genetic diversity found in the world-wide population revealed by human genome sequencing efforts and the highly variable response of the disease population to therapeutics. An ever-growing body of evidence has shown ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz026
更新日期:2019-06-15 00:00:00
abstract::Despite the clinical importance of human aneuploidy, we know little of the causes of mammalian non-disjunction. In part, this reflects the fact that, unlike lower organisms, segregation 'impaired' chromosomes are virtually non-existent in mammals. To address this issue, we have studied the mouse Y chromosome on the BA...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.9.963
更新日期:2001-04-15 00:00:00
abstract::Actinic keratosis (AK) is a pre-malignant skin disease, highly prevalent in elderly Europeans. This study investigates genetic susceptibility to AK with a genome-wide association study (GWAS). A full body skin examination was performed in 3194 elderly individuals from the Rotterdam Study (RS) of exclusive north-wester...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv076
更新日期:2015-06-01 00:00:00
abstract::Genetic and environmental influences are thought to interact in their contribution to the etiology of major neuropsychiatric disorders. One of the best replicated findings obtained in genome-wide association studies are genetic variants in the CACNA1C gene. Here, we used our constitutive heterozygous Cacna1c rat model...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz235
更新日期:2019-12-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddx205
更新日期:2017-08-01 00:00:00
abstract::The diastrophic dysplasia sulfate transporter (DTDST) gene encodes a transmembrane protein that transports sulfate into chondrocytes to maintain adequate sulfation of proteoglycans. Mutations in this gene are responsible for four recessively inherited chondrodysplasias that include diastrophic dysplasia, multiple epip...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.14.1485
更新日期:2001-07-01 00:00:00
abstract::Chromosomal common fragile sites (CFSs) are genetically unstable regions of the genome that are induced by conditions that impair DNA replication. In this report, we show that treatment with the DNA polymerase inhibitor, aphidicolin (APH), slows the replication rate throughout S phase. To investigate the unusual sensi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp470
更新日期:2010-01-01 00:00:00
abstract::Mutations in genes encoding the epsilon, delta, beta and alpha subunits of the end plate acetylcholine (ACh) receptor (AChR) are described and functionally characterized in three slow-channel congenital myasthenic syndrome patients. All three had prolonged end plate currents and AChR channel opening episodes and an en...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.9.1217
更新日期:1996-09-01 00:00:00
abstract::Defects in FAM161A, a protein of unknown function localized at the cilium of retinal photoreceptor cells, cause retinitis pigmentosa, a form of hereditary blindness. By using different fragments of this protein as baits to screen cDNA libraries of human and bovine retinas, we defined a yeast two-hybrid-based FAM161A i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv085
更新日期:2015-06-15 00:00:00
abstract::Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. Using an assay that combines tRNA oxidation and circularization we have determined the relative amounts and states of aminoacylation of mutant and wild-type tRNAs in tissue samples from patients with MELAS syndrome (mi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.4.467
更新日期:2000-03-01 00:00:00
abstract::Huntington's disease (HD) is caused by the expansion mutation above a length threshold of a polyglutamine (polyQ) stretch in the huntingtin (Htt) protein. Mutant Htt (mHtt) pathogenicity is proposed to rely on its malfunction and propensity to misfold and aggregate. Htt has scaffolding properties and has been reported...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr178
更新日期:2011-07-15 00:00:00
abstract::Meiotic crossovers in the human genome cluster into highly localized hotspots identifiable indirectly from patterns of DNA diversity and directly by high-resolution sperm typing. Little is known about factors that control hotspot activity and the apparently rapid turnover of hotspots during recent evolution. Clues can...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl063
更新日期:2006-05-01 00:00:00
abstract::The biogenesis of the mitochondrial inner membrane is dependent on two distinct 70 kDa protein complexes. TIMM8a partners with TIMM13 in the mitochondrial intermembrane space to form a 70 kDa complex and facilitates the import of the inner membrane substrate TIMM23. We have identified a new class of substrates, citrin...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh217
更新日期:2004-09-15 00:00:00
abstract::Missing teeth (hypodontia and oligodontia) are a common developmental abnormality in humans and heterozygous mutations of PAX9 have recently been shown to underlie a number of familial, non-syndromic cases. Whereas PAX9 haploinsufficiency has been suggested as the underlying genetic mechanism, it is not known how this...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi388
更新日期:2005-12-01 00:00:00
abstract::Gene amplification is a common phenomenon in malignant neoplasms of all types. One mechanism behind increased gene copy number is the formation of ring chromosomes. Such structures are mitotically unstable and during tumor progression they accumulate material from many different parts of the genome. Hence, their conte...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt479
更新日期:2014-02-15 00:00:00
abstract::Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are observed in the striatum. Here we show dramatic mutation length increases (gai...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2003-12-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2013-08-15 00:00:00
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
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