Abstract:
:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disease that has been linked to deletions within a tandem array of 3.2 kb repeats adjacent to the telomere of 4q. These repeats are also present in other locations in the human genome, including the short arms of all the acrocentric chromosomes. Here, we examine two models for the role of this repeat in FSHD. First, because of the extensive similarity between the 3.2 kb repeats on 4q and those adjacent to rDNA on the acrocentric chromosomes, we investigated whether the FSHD region on 4q is involved in sub-nuclear localization, specifically to the nucleolus. The results likely exclude any involvement of nucleolar localization in the development of FSHD. Second, we investigated a model that suggests that a functional gene may be buried within the tandem array of 3.2 kb repeats. Toward this end, we evaluated the evolutionary conservation of the repeat and a double homeodomain sequence within the repeat in a variety of primate species. The genomic organization of the 3.2 kb repeat in humans, great apes and lower primates identified the FSHD-associated repeat on chromosome 4q as the likely ancestral copy. The sequence of the rhesus monkey double homeodomain reveals significant sequence identity with the human 4q sequence. These results strongly suggest a functional role for a component of the FSHD-associated repeat.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Winokur ST,Bengtsson U,Vargas JC,Wasmuth JJ,Altherr MR,Weiffenbach B,Jacobsen SJdoi
10.1093/hmg/5.10.1567subject
Has Abstractpub_date
1996-10-01 00:00:00pages
1567-75issue
10eissn
0964-6906issn
1460-2083journal_volume
5pub_type
杂志文章abstract::Uniparental disomy (UPD) is defined as the inheritance of both homologs of a given genomic region from only one parent. The majority of UPD includes an entire chromosome. However, the extent of UPD is sometimes limited to a subchromosomal region (segmental UPD). Mosaic paternal UPD (pUPD) of chromosome 11 is found in ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw023
更新日期:2016-04-01 00:00:00
abstract::Mammalian oocytes are arrested at the prophase of meiosis I during fetal or postnatal development, and the meiosis is resumed by the preovulatory surge of luteinizing hormone. The in vivo functional roles of cyclin-dependent kinases (Cdks) during the resumption of meiosis in mammalian oocytes are largely unknown. Prev...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds061
更新日期:2012-06-01 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::Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder that can lead to sudden death, with a prevalence of 1:5000 in Caucasian population and affecting mainly male patients in their third to fourth decade of life. BrS is inherited as an autosomal dominant trait; however, to date genetic bases have been onl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv302
更新日期:2015-10-15 00:00:00
abstract::A transcription map of the Huntington disease gene region was generated by a direct cDNA selection strategy using genomic DNA from the 4p16.3 region surrounding the D4S95 and D4S127 loci. A total of 58 cDNA fragments were obtained from cDNAs derived from fetal brain, frontal cortex, liver and bone marrow following hyb...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.7.901
更新日期:1993-07-01 00:00:00
abstract::Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (SMN1). SMN-restoring therapies have recently emerged; however, preclinical and clinical studies revealed a limited therapeutic time window and systemic aspects of the disease. This raises a fundamental question of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa146
更新日期:2020-09-29 00:00:00
abstract::Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene account for >70% of X-linked retinitis pigmentosa (XLRP) and 15-20% of all inherited retinal degeneration. Gene replacement therapy for RPGR-XLRP was hampered by the relatively slow disease progression in mouse models and by difficulties in cloning the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv134
更新日期:2015-07-15 00:00:00
abstract::Grb10-Interacting GYF Protein 2 (GIGYF2) was initially identified through its interaction with Grb10, an adapter protein that binds activated IGF-I and insulin receptors. The GIGYF2 gene maps to human chromosome 2q37 within a region linked to familial Parkinson's disease (PARK11 locus), and association of GIGYF2 mutat...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp430
更新日期:2009-12-01 00:00:00
abstract::Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death are poorly understood, and consequently, there are no treatments available. Previous studies sugg...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw219
更新日期:2016-09-01 00:00:00
abstract::Mitochondrial dysfunction and oxidative stress are central to the molecular pathology of many human diseases. Riboflavin responsive multiple acyl-CoA dehydrogenation deficiency (RR-MADD) is in most cases caused by variations in the gene coding for electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). Curr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu146
更新日期:2014-08-15 00:00:00
abstract::Huntington disease (HD) is a genetic neurodegenerative disorder for which there is currently no cure and no way to stop or even slow the brain changes it causes. In the present study, we aimed to investigate whether FTY720, the first approved oral therapy for multiple sclerosis, may be effective in HD models and event...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt615
更新日期:2014-05-01 00:00:00
abstract::Pre-B cell leukemia factor 1 (PBX1) is an essential developmental transcription factor, mutations in which have recently been associated with CAKUTHED syndrome, characterized by multiple congenital defects including congenital heart disease (CHD). During analysis of a whole-exome-sequenced cohort of heterogeneous CHD ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz231
更新日期:2020-05-08 00:00:00
abstract::Uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies including medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Symptoms include renal salt wasting, hyperuricemia, gout, hypertension and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq077
更新日期:2010-05-15 00:00:00
abstract::Mitochondria contain a dedicated translation system, which is responsible for the intramitochondrial synthesis of 13 mitochondrial DNA (mtDNA)-encoded polypeptides essential for the biogenesis of oxidative phosphorylation (OXPHOS) complexes I and III-V. Mutations in nuclear genes encoding factors involved in mitochond...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy441
更新日期:2019-05-01 00:00:00
abstract::Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE le...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.1.27
更新日期:1998-01-01 00:00:00
abstract::The comparison of several statistical methods currently used for detection of differentially expressed genes was attempted both by a simulation approach and by the analysis of data sets of human expressed sequence tags, obtained from UniGene. In the simulated mixed case, mimicking a situation close to reality, the gen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.19.2133
更新日期:2001-09-15 00:00:00
abstract::We, amongst others, have shown that CC homozygosity at the -22C>T promoter polymorphism in presenilin 1 (PSEN1) is associated with increased risk for Alzheimer's disease (AD). Also, studies in AD brains suggested that CC homozygosity increased the risk for AD by increasing the Abeta load. We characterized the PSEN1 pr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg098
更新日期:2003-04-15 00:00:00
abstract::Polyglutamine diseases are a family of nine neurodegenerative disorders caused by expansion in different genes of a CAG triplet repeat stretch, which encodes an elongated polyglutamine tract. This polyglutamine tract is thought to confer a toxic gain of function to the bearing proteins, which leads to late onset and p...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddn412
更新日期:2009-04-15 00:00:00
abstract::Mutations in RP2 cause the second most frequent form of X-linked retinitis pigmentosa, a severe retinal degeneration that leads to loss of visual acuity and blindness. The RP2 gene encodes a protein with homology to cofactor C, a tubulin-folding chaperone. By searching protein sequence databases, we identified a whole...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.11.1177
更新日期:2001-05-15 00:00:00
abstract::Fragile X Syndrome (FXS) is a learning disability seen in individuals who have >200 CGG•CCG repeats in the 5' untranslated region of the X-linked FMR1 gene. Such alleles are associated with a fragile site, FRAXA, a gap or constriction in the chromosome that is coincident with the repeat and is induced by folate stress...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu006
更新日期:2014-06-01 00:00:00
abstract::Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disease caused by mutations in the gene encoding protein kinase C gamma (PKC gamma). We report an SCA14 family with a novel deletion of a termination-codon-containing region, resulting in a missense change and a C-terminal 13-amino-acid extension with inc...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp298
更新日期:2009-10-01 00:00:00
abstract::Changes in gene expression resulting from epigenetic and/or genetic changes play an important role in the evolutionary divergence of phenotypes. To explore how epigenetic and genetic changes are linked during primate evolution, we have compared the genome-wide DNA methylation profiles (methylomes) of humans and chimpa...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx236
更新日期:2017-09-15 00:00:00
abstract::Biased segregation of mitochondrial DNA variants has been widely documented, but little was known about its molecular basis. We set out to test the hypothesis that altering the balance between mitochondrial fusion and fission could influence the segregation of mutant and wild-type mtDNA variants, because it would modi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp281
更新日期:2009-09-15 00:00:00
abstract::Two common inflammatory skin disorders with impaired barrier, atopic dermatitis (AD) and psoriasis, share distinct genetic linkage to the Epidermal Differentiation Complex (EDC) locus on 1q21. The EDC is comprised of tandemly arrayed gene families encoding proteins involved in skin cell differentiation. Discovery of s...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq019
更新日期:2010-04-15 00:00:00
abstract::Cytosolic accumulation of TAR DNA binding protein 43 (TDP-43) is a major neuropathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the mechanisms involved in TDP-43 accumulation remain largely unknown. Previously, we reported that inhibitors of cyclin-depen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu578
更新日期:2015-03-15 00:00:00
abstract::Mutations in the survival motor neuron (SMN1) gene lead to the neuromuscular disease spinal muscular atrophy (SMA). Although SMA is primarily considered as a motor neuron disease, the importance of muscle defects in its pathogenesis has not been fully examined. We use both primary cell culture and two different SMA mo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu142
更新日期:2014-08-15 00:00:00
abstract::Friedreich ataxia (FRDA), a progressive neurodegenerative disorder associated with cardiomyopathy, is caused by severely reduced frataxin, a mitochondrial protein involved in Fe-S cluster assembly. We have recently generated mouse models that reproduce important progressive pathological and biochemical features of the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh114
更新日期:2004-05-15 00:00:00
abstract::The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history and long-term health outcomes of 300,000 residents of Taiwan. We describe here an investigation of the population structure of Han Chines...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw346
更新日期:2016-12-15 00:00:00
abstract::The short-rib polydactyly syndromes (SRPS) encompass a radiographically and genetically heterogeneous group of skeletal ciliopathies that are characterized by a long narrow chest, short extremities, and variable occurrence of polydactyly. Radiographic abnormalities include undermineralization of the calvarium, shorten...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw241
更新日期:2016-09-15 00:00:00
abstract::We have used the direct cDNA screening protocol to identify sequences transcribed in cerebral cortex from a reference library of human Xq28. To derive coding sequences from these genomic clones, we first identified fragments containing transcribed sequences and subjected these to exon trapping or to partial sequencing...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.11.2019
更新日期:1994-11-01 00:00:00