Abstract:
:The planar cell polarity (PCP) pathway, incorporating non-canonical Wnt signalling, controls embryonic convergent (CE) extension, polarized cell division and ciliary orientation. It also limits diameters of differentiating renal tubules, with mutation of certain components of the pathway causing cystic kidneys. Mutations in mouse Vangl genes encoding core PCP proteins cause neural tube defects (NTDs) and Vangl2 mutations also impair branching of embryonic mouse lung airways. Embryonic metanephric kidneys also undergo branching morphogenesis and Vangl2 is known to be expressed in ureteric bud/collecting duct and metanephric mesenchymal/nephron lineages. These observations led us to investigate metanephroi in Vangl2 mutant mice, Loop-tail (Lp). Although ureteric bud formation is normal in Vangl2(Lp/Lp) embryos, subsequent in vivo and in vitro branching morphogenesis is impaired. Null mutant kidneys are short, consistent with a CE defect. Differentiating glomerular epithelia express several PCP genes (Vangl1/2, Celsr1, Scrib, Mpk1/2 and Fat4) and glomeruli in Vangl2(Lp/Lp) fetuses are smaller and contain less prominent capillary loops than wild-type littermates. Furthermore, Vangl2(Lp/+) kidneys had modest reduction in glomerular numbers postnatally. Vangl2(Lp/Lp) metanephroi contained occasional dilated tubules but no overt cystic phenotype. These data show for the first time that a PCP gene is required for normal morphogenesis of both the ureteric bud and metanephric mesenchyme-derived structures. It has long been recognized that certain individuals with NTDs are born with malformed kidneys, and recent studies have discovered VANGL mutations in some NTD patients. On the basis of our mutant mouse study, we suggest that PCP pathway mutations should be sought when NTD and renal malformation co-exist.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Yates LL,Papakrivopoulou J,Long DA,Goggolidou P,Connolly JO,Woolf AS,Dean CHdoi
10.1093/hmg/ddq397subject
Has Abstractpub_date
2010-12-01 00:00:00pages
4663-76issue
23eissn
0964-6906issn
1460-2083pii
ddq397journal_volume
19pub_type
杂志文章abstract::Fourteen neurological diseases have been associated with the expansion of trinucleotide repeat regions. These diseases have been categorized into those that give rise to the translation of toxic polyglutamine proteins and those that are untranslated. Thus far, compelling evidence has not surfaced for the inclusion of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.15.1531
更新日期:2001-07-15 00:00:00
abstract::Nance-Horan syndrome (NHS) is an X-linked developmental disorder, characterized by bilateral congenital cataracts, dental anomalies, facial dysmorphism and mental retardation. Null mutations in a novel gene, NHS, cause the syndrome. The NHS gene appears to have multiple isoforms as a result of alternative transcriptio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq125
更新日期:2010-06-15 00:00:00
abstract::We recently reported that mutations in the widely expressed nuclear protein TOPORS (topoisomerase I-binding arginine/serine rich) are associated with autosomal dominant retinal degeneration. However, the precise localization and a functional role of TOPORS in the retina remain unknown. Here, we demonstrate that TOPORS...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq543
更新日期:2011-03-01 00:00:00
abstract::Waardenburg syndrome type 2 (WS2) is an autosomal dominant disorder characterized by a combination of pigmentary and auditory abnormalities. Approximately 20% of WS2 cases are associated with mutations in the gene encoding microphthalmia-associated transcription factor (MITF). MITF plays a critical role in the develop...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.8.1431
更新日期:1999-08-01 00:00:00
abstract::PTEN-induced putative kinase 1 (PINK1) and Parkin act in a common pathway to regulate mitochondrial dynamics, the involvement of which in the pathogenesis of Parkinson's disease (PD) is increasingly being appreciated. However, how the PINK1/Parkin pathway influences mitochondrial function is not well understood, and t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr235
更新日期:2011-08-15 00:00:00
abstract::Mutations in the human PAX6 gene produce various phenotypes, including aniridia, Peters' anomaly, autosomal dominant keratitis and familial foveal dysplasia. The various phenotypes may arise from different mutations in the same gene. To test this theory, we performed a functional analysis of two missense mutations in ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.3.381
更新日期:1997-03-01 00:00:00
abstract::Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion regi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp042
更新日期:2009-04-15 00:00:00
abstract::Costello syndrome (CS) is a developmental disorder characterized by postnatal reduced growth, facial dysmorphism, cardiac defects, mental retardation and skin and musculo-skeletal defects. CS is caused by HRAS germline mutations. In the majority of cases, mutations affect Gly(12) and Gly(13) and are associated with a ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp548
更新日期:2010-03-01 00:00:00
abstract::Anti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the foetus and is an emerging biomarker of postnatal reproductive function in females. Due to a paucity of adequately sized studies, the genetic determinants of circulating AMH levels are poorly characterized. In samples from 2815 adol...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv465
更新日期:2016-01-15 00:00:00
abstract::Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from seven European popula...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn351
更新日期:2009-03-01 00:00:00
abstract::A vast portion of intellectual disability and autism spectrum disorders is genetically caused by mutations in chromatin modulators. These proteins play key roles in development and are also highly expressed in the adult brain. Specifically, the pivotal role of chromatin regulation in transcription has placed enhancers...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddz196
更新日期:2019-11-21 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin. Several downstream consequences of dystrophin deficiency are triggers of endoplasmic reticulum (ER) stress, including loss of calcium homeostasis, hypoxia and oxidative stress. During ER stress, misfolded prote...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu249
更新日期:2014-10-15 00:00:00
abstract::Single-nucleotide polymorphism (SNP) tagging is widely used as a way of saving genotyping costs in association studies. A number of different tagging methods have been developed to reduce the number of markers to be genotyped while maintaining power for detecting effects on non-assayed SNPs. How the different methods ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi309
更新日期:2005-09-15 00:00:00
abstract::Aneuploidy is prevalent in human embryos and is the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing with maternal age. Superimposed on these meiotic aneuploidies are frequent errors occurring during early mitotic divisions, contributing to widespread chromosomal mosaicism. Here we...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy147
更新日期:2018-07-15 00:00:00
abstract::Mutations in the gene encoding the inner nuclear membrane proteins lamins A and C produce cardiac and skeletal muscle dysfunction referred to as Emery Dreifuss muscular dystrophy. Lamins A and C participate in the LINC complex that, along with the nesprin and SUN proteins, LInk the Nucleoskeleton with the Cytoskeleton...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn386
更新日期:2009-02-15 00:00:00
abstract::While constructing a cDNA library of human embryos, we have isolated a clone homologous to jumonji, a mouse gene required for neural tube formation. We have determined the complete coding sequence of the human homologue (JMJ) and deduced the amino acid sequence of the putative protein. We show here that human and mous...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.10.1637
更新日期:1996-10-01 00:00:00
abstract::Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contri...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr593
更新日期:2012-04-01 00:00:00
abstract::A family of growth arrest specific (Gas) genes was operationally defined on the basis of the strategy utilized to isolate them e.g. differential expression in quiescent and growing cells. Our interest in the Gas-3 gene was prompted by our previously reported localization of the gene on the mouse chromosome 11.44 +/- 1...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/1.5.331
更新日期:1992-08-01 00:00:00
abstract::In humans, the concerted action of at least 13 different peroxisomal PEX proteins is needed for proper peroxisome biogenesis. Mutations in any of these PEX genes can lead to lethal neurometabolic disorders of the Zellweger syndrome spectrum (ZSS). Previously, we identified the W313G mutation located within the SH3 dom...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt238
更新日期:2013-10-01 00:00:00
abstract::We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a min...
journal_title:Human molecular genetics
pub_type: 杂志文章,多中心研究
doi:10.1093/hmg/ddt403
更新日期:2014-01-01 00:00:00
abstract::Deletion of the distal short arm of chromosome 9 (9p) has been reported in a number of cases to be associated with gonadal dysgenesis and XY sex reversal, suggesting that this region contains one or more genes required in two copies for normal testis development. Recent studies have greatly narrowed the interval conta...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.6.989
更新日期:1999-06-01 00:00:00
abstract::By sequencing 11,405 individual expressed sequence tags (ESTs) from a cDNA library of a human skeletal muscle, we identified 1945 individual transcripts, 725 of which showed no correspondence with known human genes. We report here the chromosomal localization of 267 of these, obtained by radiation hybrid (RH) mapping....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.9.1445
更新日期:1997-09-01 00:00:00
abstract::Huntington's disease (HD) is an autosomal inherited neurological disease caused by a CAG-repeat expansion in the first exon of huntingtin gene encoding for the huntingtin protein (Htt). In HD, there is an accumulation of intracellular aggregates of mutant Htt that negatively influence cellular functions. The aggregate...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu317
更新日期:2014-11-15 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::The genetic defect underlying myotonic dystrophy (DM) has been identified as the expansion of an unstable trinucleotide repeat sequence, and this discovery has led to new approaches to diagnosis and genetic counselling in families with the disorder. We report the genetic analysis of a consanguineous DM family in which...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.6.711
更新日期:1993-06-01 00:00:00
abstract::Recent studies suggest that the genome is organized into blocks of haplotypes, and efforts to create a genome-wide haplotype map of single-nucleotide polymorphisms (SNPs) are already underway. Haplotype blocks are defined algorithmically and to date several algorithms have been proposed. However, little is known about...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh035
更新日期:2004-02-01 00:00:00
abstract::Several human inherited diseases have been localized to the Xq13.3 region of the human X chromosome (X-linked dystonia with Parkinsonism, sideroblastic anemia, SCID, Menkes disease and X-linked mental retardation loci). Genes involved in the phenotypes have been isolated for only two of them (Menkes and SCIDX). It was...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.1.39
更新日期:1994-01-01 00:00:00
abstract::The huntingtin interacting protein (HIP1) is enriched in membrane-containing cell fractions and has been implicated in vesicle trafficking. It is a multidomain protein containing an N-terminal ENTH domain, a central coiled-coil forming region and a C-terminal actin-binding domain. In the present study we have identifi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.17.1807
更新日期:2001-08-15 00:00:00
abstract::FOXP transcription factors play important roles in neurodevelopment, but little is known about how their transcriptional activity is regulated. FOXP proteins cooperatively regulate gene expression by forming homo- and hetero-dimers with each other. Physical associations with other transcription factors might also modu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy035
更新日期:2018-04-01 00:00:00
abstract::Muscle-eye-brain disease (MEB), an autosomal recessive disorder prevalent in Finland, is characterized by congenital muscular dystrophy, brain malformation and ocular abnormalities. Since the MEB phenotype overlaps substantially with those of Fukuyama-type congenital muscular dystrophy (FCMD) and Walker-Warburg syndro...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg043
更新日期:2003-03-01 00:00:00