Abstract:
:Pallister-Hall syndrome (PHS) is a rare disorder caused by mutations in GLI3 that produce a transcriptional repressor (GLI3R). Individuals with PHS present with a variably penetrant variety of urogenital system malformations, including renal aplasia or hypoplasia, hydroureter, hydronephrosis or a common urogenital sinus. The embryologic mechanisms controlled by GLI3R that result in these pathologic phenotypes are undefined. We demonstrate that germline expression of GLI3R causes renal hypoplasia, associated with decreased nephron number, and hydroureter and hydronephrosis, caused by blind-ending ureters. Mice with obligate GLI3R expression also displayed duplication of the ureters that was caused by aberrant common nephric duct patterning and ureteric stalk outgrowth. These developmental abnormalities are associated with suppressed Hedgehog signaling activity in the cloaca and adjacent vesicular mesenchyme. Mice with conditional expression of GLI3R were utilized to identify lineage-specific effects of GLI3R. In the ureteric bud, GLI3R expression decreased branching morphogenesis. In Six2-positive nephrogenic progenitors, GLI3R decreased progenitor cell proliferation reducing the number of nephrogenic precursor structures. Using mutant mice with Gli3R and Gli3 null alleles, we demonstrate that urogenital system patterning and development is controlled by the levels of GLI3R and not by an absence of full-length GLI3. We conclude that the urogenital system phenotypes observed in PHS are caused by GLI3R-dependent perturbations in nephric duct patterning, renal branching morphogenesis and nephrogenic progenitor self-renewal.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Blake J,Hu D,Cain JE,Rosenblum NDdoi
10.1093/hmg/ddv483subject
Has Abstractpub_date
2016-02-01 00:00:00pages
437-47issue
3eissn
0964-6906issn
1460-2083pii
ddv483journal_volume
25pub_type
杂志文章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::Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl487
更新日期:2007-03-15 00:00:00
abstract::Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: alpha 1(V)2 alpha 2(V) or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic polymorphisms at the pro alph...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.11.1733
更新日期:1996-11-01 00:00:00
abstract::Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterized by progressive bone marrow failure, multiple congenital abnormalities, and an increased risk of cancer. FA cells are characterized by chromosomal instability and hypersensitivity to DNA interstrand crosslinking agents. At least eight complem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg266
更新日期:2003-10-01 00:00:00
abstract::An improved understanding of the expression of the cystic fibrosis gene (CFTR) will assist our approach to preventing the organ damage caused by cystic fibrosis (CF). We have studied the expression of CFTR in human fetal tissues at different gestational ages using in situ hybridization to detect CFTR mRNA. CFTR was pr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.3.219
更新日期:1993-03-01 00:00:00
abstract::Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.11.1779
更新日期:1998-10-01 00:00:00
abstract::Microsatellite instability (MSI) characterizes tumors arising in patients with hereditary non-polyposis colorectal cancer (HNPCC) syndrome. HNPCC is a hereditary autosomal dominant disease caused by germline mutations in genes from the DNA (MMR) mismatch repair system. In these tumors, the loss of MMR compromises the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi021
更新日期:2005-01-15 00:00:00
abstract::Fragile X syndrome, a common form of inherited mental retardation, is caused by loss of the fragile X mental retardation protein (FMRP). As a selective RNA-binding protein, FMRP is localized predominately in cytoplasm, where it regulates translational control. However, there is a small portion of FMRP present in the n...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu241
更新日期:2014-10-01 00:00:00
abstract::Mutations in the gene encoding myotubularin-related protein 2 (MTMR2) are responsible for autosomal recessive Charcot-Marie-Tooth disease type 4B1 (CMT4B1), a severe hereditary motor and sensory neuropathy characterized by focally folded myelin sheaths and demyelination. MTMR2 belongs to the myotubularin family, which...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.13.1569
更新日期:2002-06-15 00:00:00
abstract::The role of renin binding protein (RnBP) in human (patho)physiology, despite its biochemical characterization, is as yet unclear. RnBP has been shown to bind and inactivate renin, a key player of the blood pressure regulating renin-angiotensin system. This renders the RnBP gene a promising candidate gene in human hype...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.9.1527
更新日期:1997-09-01 00:00:00
abstract::Recombination was measured across nine intervals in the human beta-globin gene cluster by single-sperm analysis. A recombination fraction of approximately 0.9% was calculated across an approximately 11 kb region using a new method to estimate recombination fractions from single-sperm typing data. No recombination was ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.3.207
更新日期:2002-02-01 00:00:00
abstract::Dominant mutations in the gene encoding the ubiquitously-expressed splicing factor PRPF31 cause retinitis pigmentosa, a form of hereditary retinal degeneration, with reduced penetrance. We and others have previously shown that penetrance is tightly correlated with PRPF31 expression, as lymphoblastoid cell lines (LCLs)...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn212
更新日期:2008-10-15 00:00:00
abstract::A cDNA for Fanconi anaemia complementation group C (FACC) has recently been cloned. We have now isolated a yeast artificial chromosome clone containing the FACC gene, and used vectorette PCR to determine its exon structure. The 1674-nucleotide coding sequence of the gene is highly interrupted, and contains 14 exons ra...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.1.35
更新日期:1993-01-01 00:00:00
abstract::The FMR1 gene, associated with fragile X syndrome, has recently been cloned and the sequence of partial cDNA clones is known. We have determined additional cDNA sequences both at the 5' and 3' end. We have characterized the expressed gene by means of RT-PCR in various tissues and have found that alternative splicing t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.4.399
更新日期:1993-04-01 00:00:00
abstract::Research of cilia has gained significant momentum in the last 15 years, as an increasing number of human genetic diseases were found to be caused by disruption of a protein that localizes to cilia. These ciliopathies are as diverse as the functions of the associated proteins, covering a spectrum of overlapping phenoty...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddr354
更新日期:2011-10-15 00:00:00
abstract::X-linked dilated cardiomyopathy (XLDCM) is a clinical phenotype of dystrophinopathy which is characterized by preferential myocardial involvement without any overt clinical signs of skeletal myopathy. To date, several mutations in the Duchenne muscular dystrophy gene, DMD , have been identified in patients with XLDCM,...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.7.1129
更新日期:1998-07-01 00:00:00
abstract::We have established a Drosophila model of Gerstmann-Sträussler-Scheinker (GSS) syndrome by expressing mouse prion protein (PrP) having leucine substitution at residue 101 (MoPrP(P101L)). Flies expressing MoPrP(P101L), but not wild-type MoPrP (MoPrP(3F4)), showed severe defects in climbing ability and early death. Expr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq379
更新日期:2010-11-15 00:00:00
abstract::Protein-protein interactions are fundamental to all biological processes, and a comprehensive determination of all protein-protein interactions that can take place in an organism provides a framework for understanding biology as an integrated system. The availability of genome-scale sets of cloned open reading frames ...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddi335
更新日期:2005-10-15 00:00:00
abstract::Dyskeratosis congenita (DC) is a rare genetic syndrome that gives rise to a variety of disorders in affected individuals. Remarkably, all causative gene mutations identified to date share a link to telomere/telomerase biology. We found that the most prevalent dyskerin mutation in DC (A353V) did not affect formation of...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp551
更新日期:2010-03-01 00:00:00
abstract::Beside the well-known polyglutamine expansions involved in several neurodegenerative disorders, convergent recent findings pointed to the expansion of polyalanine stretches as a disease mechanism in congenital malformations, skeletal dysplasia and nervous system anomalies. Polyalanine stretches have been predicted in ...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddh251
更新日期:2004-10-01 00:00:00
abstract::The genomic instability of persons with Bloom's syndrome (BS) features particularly an increased number of sister-chromatid exchanges (SCEs). The primary cause of the genomic instability is mutation at BLM, which encodes a DNA helicase of the RecQ family. BLM interacts with Topoisomerase IIIalpha (Topo IIIalpha), and ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.12.1287
更新日期:2001-06-01 00:00:00
abstract::Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-gl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu586
更新日期:2015-03-15 00:00:00
abstract::Closure of ATP-sensitive potassium channels in pancreatic islet beta-cells initiates a cascade of events that leads to insulin secretion. beta-Cell ATP-sensitive potassium currents can be reconstituted by coexpression of the inward rectifier Kir6.2 and the sulfonylurea receptor (SUR), a member of the ATP-binding casse...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.11.1809
更新日期:1996-11-01 00:00:00
abstract::Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder, characterised by the association of branchial, otic and renal anomalies with variable degrees of severity. We have recently identified EYA1 , a human homologue of the Drosophila eyes absent gene, as the gene underlying this syndrome. The products of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.13.2247
更新日期:1997-12-01 00:00:00
abstract::Glaucoma is the leading cause of irreversible blindness worldwide. Although most glaucoma patients are elderly, congenital glaucoma and glaucomas of childhood are also important causes of visual disability. Primary congenital glaucoma (PCG) is isolated, non-syndromic glaucoma that occurs in the first three years of li...
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::Steroid 11 beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, the inherited inability to synthesize cortisol. Severely affected patients carry mutations in the CYB11B1 gene that destroy enzymatic activity. Such patients have signs of androgen excess and usually have hyperten...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.11.1829
更新日期:1997-10-01 00:00:00
abstract::Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are two human autosomal dominant skeletal dysplasias characterized by variable short stature, joint laxity and early-onset degenerative joint disease. Both disorders can result from mut-ations in the gene for cartilage oligomeric matrix protein (COMP...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.1.123
更新日期:1999-01-01 00:00:00
abstract::Glucocorticoids are beneficial in Duchenne muscular dystrophy (DMD). Osteopontin (OPN), the protein product of SPP1, plays a role in DMD pathology modulating muscle inflammation and regeneration. A polymorphism in the SPP1 promoter (rs28357094) has been recognized as a genetic modifier of DMD, and there is evidence su...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx218
更新日期:2017-09-01 00:00:00
abstract::The DAZ gene cluster on the human Y chromosome is a candidate for the Azoospermia Factor (AZFc). According to the current evolutionary model, the DAZ cluster derived from the autosomal homolog DAZL1 through duplications and rearrangements and is confined to Old World monkeys, apes and humans. To study functional and e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.11.2017
更新日期:1999-10-01 00:00:00
abstract::Biliary atresia (BA) is characterized by the progressive fibrosclerosing obliteration of the extrahepatic biliary system during the first few weeks of life. Despite early diagnosis and prompt surgical intervention, the disease progresses to cirrhosis in many patients. The current theory for the pathogenesis of BA prop...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq196
更新日期:2010-07-15 00:00:00