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 and analysis by Grail. In a preliminary analysis of three clones, coding sequences from two novel genes expressed in brain were identified. This method allows the rapid identification of coding sequences of genes expressed in specific tissues without recourse to cDNA libraries. The approach is amenable to large scale applications and should be useful for isolating candidate disease genes and in particular for assembling integrated transcriptional maps from large genomic regions.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Lawrence BJ,Schwabe W,Kioschis P,Coy JF,Poustka A,Brennan MB,Hochgeschwender Udoi
10.1093/hmg/3.11.2019subject
Has Abstractpub_date
1994-11-01 00:00:00pages
2019-23issue
11eissn
0964-6906issn
1460-2083journal_volume
3pub_type
杂志文章abstract::Selenium (Se) is an essential trace element in human nutrition, but its role in certain health conditions, particularly among Se sufficient populations, is controversial. A genome-wide association study (GWAS) of blood Se concentrations previously identified a locus at 5q14 near BHMT. We performed a GW meta-analysis o...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddu546
更新日期:2015-03-01 00:00:00
abstract::Poly(ADP-ribose) polymerase 2 (PARP-2) is a newly discovered member of the PARP family. We report the association of PARP-2 with mammalian centromeres in a cell-cycle-dependent manner, accumulating at centromeres during prometaphase and metaphase, disassociating during anaphase, and disappearing from the centromeres b...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.19.2319
更新日期:2002-09-15 00:00:00
abstract::Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddt575
更新日期:2014-04-01 00:00:00
abstract::The X-linked retinitis pigmentosa protein RP2 is a GTPase activating protein (GAP) for the small GTPase Arl3 and both proteins are implicated in the traffic of proteins to the primary cilia. Here, we show that RP2 can facilitate the traffic of the Gβ subunit of transducin (Gβ1). Glutathione S-transferase (GST)-RP2 pul...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr520
更新日期:2012-02-15 00:00:00
abstract::Dilated cardiomyopathy (DCM) due to mutations in RBM20, a gene encoding an RNA-binding protein, is associated with high familial penetrance, risk of progressive heart failure and sudden death. Although genetic investigations and physiological models have established the linkage of RBM20 with early-onset DCM, the under...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu091
更新日期:2014-07-15 00:00:00
abstract::F1Fo-ATP synthase is a key enzyme of mitochondrial energy provision producing most of cellular ATP. So far, mitochondrial diseases caused by isolated disorders of the ATP synthase have been shown to result from mutations in mtDNA genes for the subunits ATP6 and ATP8 or in nuclear genes encoding the biogenesis factors ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq254
更新日期:2010-09-01 00:00:00
abstract::Infantile neuronal ceroid lipofuscinosis (INCL), a neurodegenerative storage disorder of childhood, is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in S-acylated (palmitoylated) proteins and its mutation causes abnormal intracellular accumulation of fatty-acy...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl105
更新日期:2006-06-01 00:00:00
abstract::Machado-Joseph disease (MJD) is a fatal, dominant neurodegenerative disorder. MJD results from polyglutamine repeat expansion in the MJD-1 gene, conferring a toxic gain of function to the ataxin-3 protein. In this study, we aimed at overexpressing ataxin-3 in the rat brain using lentiviral vectors (LV), to generate an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn106
更新日期:2008-07-15 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::The oculo-auriculo-vertebral spectrum (OAVS) (OMIM % 164210) is a common developmental disorder characterized by hemifacial microsomia, epibulbar tumours, ear malformation and vertebral anomalies. Although rare familial cases suggest that OAVS has a genetic basis, no genetic defect has been identified so far. In a pat...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi474
更新日期:2006-02-15 00:00:00
abstract::Ciliary trafficking defects underlie the pathogenesis of severe human ciliopathies, including Joubert Syndrome (JBTS), Bardet-Biedl Syndrome, and some forms of retinitis pigmentosa (RP). Mutations in the ciliary protein RPGR (retinitis pigmentosa GTPase regulator) are common causes of RP-associated photoreceptor degen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw281
更新日期:2016-10-15 00:00:00
abstract::Genomic data offer a goldmine of information for understanding the contribution of genetic variation makes to health and disease. The potential of genomic medicine, to predict, diagnose, manage and treat genetic disease, is underpinned by accurate variant interpretation. This in itself hinges on the ability to access ...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddy084
更新日期:2018-05-01 00:00:00
abstract::Peroxisome biogenesis disorders, including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease, are lethal hereditary diseases caused by abnormalities in peroxisomal assembly. To date, 12 genotypes have been identified. We now have evidence that the complete human cDNA encoding P...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.6.1077
更新日期:1999-06-01 00:00:00
abstract::The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identifi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg111
更新日期:2003-05-01 00:00:00
abstract::Most quantitative trait loci (QTL) studies have focused on detecting the genetic effects of individual QTLs. This study thoroughly dissected the genetic components of type 2 diabetic mice, including a search for epistatic interactions and multi-locus additive effects that result in variation in diabetes-related phenot...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi433
更新日期:2006-01-01 00:00:00
abstract::The fragile X syndrome results from transcriptional silencing of the FMR1 gene and the absence of its encoded FMRP protein. Two autosomal homologues of the FMR1 gene, FXR1 and FXR2, have been identified and the overall structures of the corresponding proteins are very similar to that of FMRP. Using antibodies raised a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.13.2121
更新日期:1998-12-01 00:00:00
abstract::The Smith-Lemli-Opitz syndrome (SLOS; also known as the RSH syndrome) is an autosomal recessive genetic disorder, leading to characteristic multi-organ developmental abnormalities, dysmorphic facies, limb malformations and mental retardation. Mutations in the gene for Delta(7)-dehydrocholesterol reductase (Delta(7)-re...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.9.1385
更新日期:2000-05-22 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::The first 17 amino acids of Huntington's disease (HD) protein, huntingtin, comprise an amphipathic alpha-helical domain that can target huntingtin to the endoplasmic reticulum (ER). N17 is phosphorylated at two serines, shown to be important for disease development in genetic mouse models, and shown to be modified by ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds554
更新日期:2013-04-01 00:00:00
abstract::The breast cancer susceptibility gene BRCA2 encodes a protein of 3418 amino acids which does not exhibit substantial sequence similarity to any other protein in the public databases. A dot matrix comparison of BRCA2 with itself revealed an eight times repeated motif in the segment of the protein encoded by exon 11. As...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.1.53
更新日期:1997-01-01 00:00:00
abstract::TNNI3K expression worsens disease progression in several mouse heart pathology models. TNNI3K expression also reduces the number of diploid cardiomyocytes, which may be detrimental to adult heart regeneration. However, the gene is evolutionarily conserved, suggesting a beneficial function that has remained obscure. He...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa234
更新日期:2021-01-06 00:00:00
abstract::The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression pro...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr328
更新日期:2011-10-15 00:00:00
abstract::Germline mutations in the RB1 gene confer hereditary predisposition to retinoblastoma. The majority of these mutations occur de novo and differ from one patient to another. Cytogenetics and Southern blotting were shown to detect less than 15% of constitutional rearrangements. In this study we used the polymerase chain...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.7.975
更新日期:1993-07-01 00:00:00
abstract::Genetic analysis of mouse mutants has demonstrated the importance of the homeobox genes Rpx, Lhx3 and Pit1 for anterior pituitary gland development. Pit1 mutations have also been identified in several human families with multiple pituitary hormone deficiencies. To identify additional homeobox regulators of pituitary d...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.3.457
更新日期:1997-03-01 00:00:00
abstract::Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt015
更新日期:2013-04-15 00:00:00
abstract::Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the unde...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy310
更新日期:2018-12-15 00:00:00
abstract::Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder phenotypically characterized by many features of premature aging. Most cases of HGPS are due to a heterozygous silent mutation (c.1824C>T; p.Gly608Gly) that enhances the use of an internal 5' splice site (5'SS) in exon 11 of the LMNA pre-mRNA and l...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr385
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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
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更新日期:2014-08-15 00:00:00
abstract::Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. Th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.3.221
更新日期:2001-02-01 00:00:00
abstract::Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes. The MEN1 locus has been previously localised to chromosome 11q13, and a <300 kb gene-rich region flanked centr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.7.1177
更新日期:1997-07-01 00:00:00