Abstract:
:Nineteen Wnt ligands and 10 Frizzled (Fz) receptors mediate multiple distinct cellular events during neuronal development. However, their precise roles in cell-type specification and organogenesis are poorly delineated because of overlapping functions and expression profiles. Here, we have explored the role of two closely related Frizzled receptors, Fz5 and Fz8, in mouse retinal development. We previously showed that Fz5(-/-) mice exhibit mild coloboma and microphthalmia at ~50% penetrance. Fz8 expression overlaps with Fz5 in the neural retina and optic fissure/disc. Mice lacking Fz8 show minimal eye and retinal defects. The embryos lacking both Fz5 and Fz8 die early in development, but a majority of triallelic Fz5(-/-);Fz8(+/-) mutants survive until birth. The triallelic mutant develops severe retinal coloboma and microphthalmia with full penetrance. At the cellular level, impaired neurogenesis is indicated by increased early-born retinal neurons that result from accelerated cell cycle exit of progenitors. Deficiency of apical retinal neuroepithelium is indicated by altered localization of apical junction markers, such as atypical protein kinase C, RhoA and β-catenin. Hes1 expression, which is critical for retinal progenitor expansion, is down-regulated in the triallelic mutant mouse. Furthermore, blocking Frizzled receptors in cultured retinal explants led to basally shifted divisions of retinal progenitors. Together, our studies suggest a dose-dependent regulation of signaling by Fz5 and Fz8 in optic fissure/disc formation and progenitor expansion.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Liu C,Bakeri H,Li T,Swaroop Adoi
10.1093/hmg/ddr616subject
Has Abstractpub_date
2012-04-15 00:00:00pages
1848-60issue
8eissn
0964-6906issn
1460-2083pii
ddr616journal_volume
21pub_type
杂志文章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::The gene responsible for Huntington disease has been localized to a 2.5 million base pair (Mb) region between the loci D4S10 and D4S168 on the short arm of chromosome 4. As part of a strategy to clone the HD gene on the basis of its chromosomal location, we isolated genomic DNA from the HD region as a set of overlappi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/1.3.149
更新日期:1992-06-01 00:00:00
abstract::Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A gene at Xq22.1. To determine the nature and frequency of the molecular lesions causing the classical and milder variant Fabry phenotypes, and for precise carrier detection in Fabry families, the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.10.1795
更新日期:1994-10-01 00:00:00
abstract::Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associa...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddt488
更新日期:2014-02-15 00:00:00
abstract::The Pearson marrow-pancreas syndrome (MIM 557000) is a disorder involving the hematopoietic system and the exocrine pancreas in early infancy. We have previously shown that this disease results from a defect of oxidative phosphorylation associated with deletions of the mitochondrial DNA. We present here a series of 21...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.8.1327
更新日期:1995-08-01 00:00:00
abstract::NADH-ubiquinone oxidoreductase (complex I) deficiency is amongst the most encountered defects of the mitochondrial oxidative phosphorylation (OXPHOS) system and is associated with a wide variety of clinical signs and symptoms. Mutations in complex I nuclear structural genes are the most common cause of isolated comple...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh071
更新日期:2004-03-15 00:00:00
abstract::KDM6B/JMJD3 is a histone H3 lysine demethylase with an important gene regulatory role in development and physiology. Here, we show that human JMJD3 expression is induced by the active vitamin D metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and that JMJD3 modulates the gene regulatory action of this hormone....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr399
更新日期:2011-12-01 00:00:00
abstract::NPHP4 mutations cause nephronophthisis, an autosomal recessive cystic kidney disease associated with renal fibrosis and kidney failure. The NPHP4 gene product nephrocystin-4 interacts with other nephrocystins, cytoskeletal and ciliary proteins; however, the molecular and cellular functions of nephrocystin-4 have remai...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr214
更新日期:2011-08-15 00:00:00
abstract::Disruption of the blood-brain barrier (BBB) is a serious complication frequently encountered in neurodegenerative disorders. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. It remains u...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds038
更新日期:2012-05-15 00:00:00
abstract::RAD51C was defined by Meindl et al. in 2010 as a high-risk gene involved in hereditary breast and ovarian cancers. Although this role seems to be clear, nowadays there is controversy about the indication of including the gene in routine clinical genetic testing, due to the lower prevalence or the absence of mutations ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds115
更新日期:2012-07-01 00:00:00
abstract::To identify a gene responsible for multiple endocrine neoplasia type 1 (MEN1), we attempted to isolate potentially transcribable fragments from cosmid clones derived from a region on chromosome 11q13 where genetic linkage studies and analyses of loss of heterozygosity in MEN1-associated tumors have localized the MEN1 ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.3.465
更新日期:1994-03-01 00:00:00
abstract::Spinal muscular atrophy (SMA) is a genetic disorder characterized by loss of motor neurons in the spinal cord leading to muscle atrophy and death. Although motor neurons (MNs) are the most obviously affected cells in SMA, recent evidence suggest dysfunction in multiple cell types. Astrocytes are a crucial component of...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv489
更新日期:2016-02-01 00:00:00
abstract::Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between PINK1 and parkin remains unclear. Here, we report that PINK1 regulates the E3 ubi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp501
更新日期:2010-01-15 00:00:00
abstract::Lung cancer is the leading cause of cancer death in North America. Despite advances in lung cancer treatment, the overall 5 year survival rate for those diagnosed with the disease is bleak presumably due to the late stage of diagnosis. Owing to the difficulty of early detection, preneoplastic specimens are rare. Howev...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi043
更新日期:2005-02-15 00:00:00
abstract::Little is known about the post-transcriptional mechanisms that modulate the genetic effects in the molecular pathways underlying Alzheimer disease (AD), and even less is known about how these changes might differ across diverse populations. RNA editing, the process that alters individual bases of RNA, may contribute t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz110
更新日期:2019-09-15 00:00:00
abstract::The CCG rich sequence immediately 3' to the CAG repeat that is expanded in Huntington's disease (HD) has recently been shown to be polymorphic with at least 4 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 180 HD families resident in Scotland and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.1.173
更新日期:1994-01-01 00:00:00
abstract::To determine factors governing triplet repeat expansion at FMR1, we need to understand the basis of normal variation. We have sequenced the FMR1 repeat from 102 normal X chromosomes and show that most are interrupted with a regularly spaced AGG trinucleotide giving an ordered structure to the array. Five types of arra...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.9.1553
更新日期:1994-09-01 00:00:00
abstract::Ryanodine receptor type I (RYR1)-related myopathies (RYR1 RM) are a clinically and histopathologically heterogeneous group of conditions that represent the most common subtype of childhood onset non-dystrophic muscle disorders. There are no treatments for this severe group of diseases. A major barrier to therapy devel...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz105
更新日期:2019-09-15 00:00:00
abstract::Xeroderma pigmentosum (XP) complementation group F was first reported in Japan and most XP-F patients reported to date are Japanese. The clinical features of XP-F patients are rather mild, including late onset of skin cancer. Recently a cDNA that corrects the repair deficiency of cultured XP-F cells was isolated. The ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.6.969
更新日期:1998-06-01 00:00:00
abstract::Recessive mutations in myosin 15, a class XV unconventional myosin, cause profound congenital deafness in humans and both deafness and vestibular dysfunction in mice homozygous for the shaker 2 and shaker 2(J) alleles. The shaker 2 allele is a previously described missense mutation of a highly conserved residue in the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.12.1729
更新日期:2000-07-22 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::Integrating single-cell RNA sequencing (scRNA-seq) data with genotypes obtained from DNA sequencing studies facilitates the detection of functional genetic variants underlying cell type-specific gene expression variation. Unfortunately, most existing scRNA-seq studies do not come with DNA sequencing data; thus, being ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz207
更新日期:2019-11-01 00:00:00
abstract::Niemann-Pick type C (NPC) disease is a fatal recessively inherited lysosomal cholesterol-sphingolipidosis. Mutations in the NPC1 gene cause approximately 95% of the cases, the rest being caused by NPC2 mutations. Here the molecular basis of a severe infantile form of the disease was dissected. The level of NPC1 protei...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg025
更新日期:2003-02-01 00:00:00
abstract::We have identified a rare mutation (T-45C) in the low density lipoprotein (LDL)-receptor gene in a Welsh patient with a clinical diagnosis of heterozygous familial hypercholesterolaemia (FH). The mutation is in the proximal Sp1 binding site in repeat 3 of the 42 bp region of the promoter required for sterol-dependent ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.11.2125
更新日期:1995-11-01 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::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::FcgRIIa and FcgRIIIa are potent modulators of the immune system which bind (auto)antibodies and activate immune cells. The FcgRIIa*A519G and FcgRIIIa*A559C functional variants have been associated with several immune-related diseases. We studied FcgRIIa*A519G and FcgRIIIa*A559C SNPs in type 1 diabetes (T1D), celiac di...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm194
更新日期:2007-11-01 00:00:00
abstract::Fatty liver has been associated with unfavourable metabolic changes in circulation. To provide insights in fatty liver-related metabolic deviations, we compared metabolic association profile of fatty liver versus metabolic association profiles of genotypes increasing the risk of non-alcoholic fatty liver disease (NAFL...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy124
更新日期:2018-06-15 00:00:00
abstract::Missense mutations and extra copies of the alpha-Synuclein gene result in Parkinson disease (PD). Human stem and progenitor cells can be expanded from embryonic tissues and provide a source of non-transformed neural cells to explore the effects of these pathogenic mutations specifically in human nervous tissue. We ove...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm008
更新日期:2007-03-15 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