Abstract:
:Bone mineral density (BMD) is one of the major determinants of risk for osteoporotic fracture. Multiple studies reveal that peak bone mass is under strong genetic influence. One of the major susceptibility loci for peak spine BMD has been mapped to chromosome 1q21-q23 in the Caucasian population. We have previously replicated this finding in Southern Chinese pedigrees and detected a maximum multipoint log of odds (LOD) score of 2.36 in this region. To further fine-map this region, 380 single-nucleotide polymorphic (SNP) markers were genotyped in 610 sibpairs from 231 families. Several markers were identified in the association analysis as important candidates underlying BMD variation. Among them, successful replication was demonstrated for SNPs in pre-B-cell leukemia homeobox 1 (PBX1) gene in two other unrelated case-control cohorts. The functional role of PBX1 in bone metabolism was examined in vitro using human bone-derived cells (HBDC) and murine MC3T3-E1 pre-osteoblasts. PBX1 mRNA was constitutively expressed in both HBDC and MC3T3-E1 cells. Immunostaining revealed that PBX1 is localized in the nucleus compartment. Silencing of PBX1 by RNAi in MC3T3-E1 cells decreased the expression of Runx2 and Osterix, the critical transcription factors for osteogenesis, but accelerated cell proliferation and bone nodule formation. Overall, our data suggest a genetic and functional association of PBX1 with BMD.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Cheung CL,Chan BY,Chan V,Ikegawa S,Kou I,Ngai H,Smith D,Luk KD,Huang QY,Mori S,Sham PC,Kung AWdoi
10.1093/hmg/ddn397subject
Has Abstractpub_date
2009-02-15 00:00:00pages
679-87issue
4eissn
0964-6906issn
1460-2083pii
ddn397journal_volume
18pub_type
杂志文章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
abstract::Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains unknown. To determ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh147
更新日期:2004-07-15 00:00:00
abstract::We introduced a targeted single base deletion at codon 307 of the rds-peripherin gene in mice, similar mutations being known to cause autosomal dominant retinitis pigmentosa (RP) in man. Histopathological and electroretinographic analysis indicate that the retinopathy in mice homozygous for the codon 307 mutation appe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.9.1005
更新日期:2002-05-01 00:00:00
abstract::Presenilins 1 and 2 (PS1/2), causative molecules for familial Alzheimer's disease (FAD), are multipass transmembrane proteins localized predominantly in the endoplasmic reticulum (ER) and Golgi apparatus. Heteromeric protein complexes containing PS1/2 are thought to participate in several functions, including intramem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi195
更新日期:2005-07-01 00:00:00
abstract::Degradation of fibrillar collagens is believed to be involved in the rupture of the fetal membranes during normal parturition and when the membranes rupture prematurely. Matrix metalloproteinase 1 (MMP1) is a key enzyme involved in extracellular matrix turnover, and genetic variation in the MMP1 promoter is associated...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm381
更新日期:2008-04-15 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::Despite the clinical importance of human aneuploidy, we know little of the causes of mammalian non-disjunction. In part, this reflects the fact that, unlike lower organisms, segregation 'impaired' chromosomes are virtually non-existent in mammals. To address this issue, we have studied the mouse Y chromosome on the BA...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.9.963
更新日期:2001-04-15 00:00:00
abstract::The DUX4 transcription factor is normally expressed in the cleavage-stage embryo and regulates genes involved in embryonic genome activation. Misexpression of DUX4 in skeletal muscle, however, is toxic and causes facioscapulohumeral muscular dystrophy (FSHD). We recently showed DUX4-induced toxicity is due, in part, t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz242
更新日期:2019-12-01 00:00:00
abstract::Lipoprotein lipase (LPL) is a 448-amino-acid head-to-tail dimeric enzyme that hydrolyzes triglycerides within capillaries. LPL is secreted by parenchymal cells into the interstitial spaces; it then binds to GPIHBP1 (glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1) on the basolateral fa...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds127
更新日期:2012-07-01 00:00:00
abstract::Although studies over the last decades have firmly connected a number of genes and molecular pathways to aging, the aging process as a whole still remains poorly understood. To gain novel insights into the mechanisms underlying aging, instead of considering aging genes individually, we studied their characteristics at...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw145
更新日期:2016-07-15 00:00:00
abstract::The presence of an extra Y chromosome in males is a relatively common occurrence, the 47,XYY karyotype being found in approximately 1 in 1000 male births. The error of disjunction must occur either during paternal meiosis II or as a post-zygotic mitotic error, both of which are rare events for other chromosomes. It is...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.12.2205
更新日期:1999-11-01 00:00:00
abstract::Mutations in enzymes involved in sphingolipid metabolism and trafficking cause a variety of neurological disorders, but details of the molecular pathophysiology remain obscure. SPTLC1 encodes one subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis. Mutations in SPTLC1 cause...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi380
更新日期:2005-11-15 00:00:00
abstract::Slow channel congenital myasthenic syndrome (SCCMS) is a disorder of the neuromuscular synapse caused by dominantly inherited missense mutations in genes that encode the muscle acetylcholine receptor (AChR) subunits. Here we investigate the potential of post-transcriptional gene silencing using RNA interference (RNAi)...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg280
更新日期:2003-10-15 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::Nuclear Factor-kappaB (NF-kappaB) is a major transcription regulator of immune response, apoptosis and cell-growth control genes, and is upregulated in inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease. The NFKB1 gene encodes the NF-kappaB p105/p50 isoforms. Genome-wide screens in IBD ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh008
更新日期:2004-01-01 00:00:00
abstract::Glomerular disease is one of the most common causes of end-stage renal failure. Increasing evidence suggests that these glomerulopathies are frequently caused by primary lesions in the renal podocytes. One of the major consequences of podocyte lesions is the accumulation of mesangial matrix in the glomerular basement ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.6.651
更新日期:2002-03-15 00:00:00
abstract::17p13.3 microduplication syndrome is a newly identified genetic disorder characterized by duplications in the 17p13.3 chromosome locus, resulting in a variety of disorders including autism spectrum disorder (ASD). Importantly, a minimum duplication region has been defined, and this region exclusively contains the gene...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw270
更新日期:2016-10-15 00:00:00
abstract::The gene encoding the gamma chain of the lymphocyte interleukin-2 receptor has been cloned and shown to be required to associate with the beta chain in order for IL-2 internalization and cell activation to occur (1). We considered this gene, IL2RG, a candidate for the X-linked form of severe combined immunodeficiency ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.8.1099
更新日期:1993-08-01 00:00:00
abstract::The autosomal recessive mouse mutation retinal degeneration 6 (rd6) causes small, white retinal spots and progressive photoreceptor degeneration similar to that observed in human flecked retinal diseases. Using a positional cloning approach, we determined that rd6 mice carry a splice donor mutation in the mouse homolo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.16.1879
更新日期:2002-08-01 00:00:00
abstract::The short stature homeobox gene SHOX encodes a transcription factor which is important for normal limb development. In humans, SHOX deficiency has been associated with various short stature syndromes including Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia and Turner syndrome as well as non-syndromic i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr030
更新日期:2011-04-15 00:00:00
abstract::The gene encoding protein kinase WNK2 was recently identified to be silenced by promoter hypermethylation in gliomas and meningiomas, suggesting a tumour-suppressor role in these brain tumours. Following experimental depletion in cell lines, WNK2 was further found to control GTP-loading of Rac1, a signalling guanosine...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds405
更新日期:2013-01-01 00:00:00
abstract::LKB1 is a serine/threonine kinase which is inactivated by mutation in the Peutz-Jeghers polyposis and cancer predisposition syndrome (PJS). We have identified a novel leucine-rich repeat containing protein, LIP1, that interacts with LKB1. The LIP1 gene consists of 25 exons, maps to human chromosome 2q36 and encodes a ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.25.2869
更新日期:2001-12-01 00:00:00
abstract::Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM 312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2 mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt640
更新日期:2014-05-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP) are two neurodegenerative disorders characterized by the accumulation of TDP-43. TDP-43 is proteolitically cleaved to generate two major C-terminal fragments of 35 and 25 kDa. The latter, known as TDP-25, is a consistent feature of FT...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv193
更新日期:2015-08-15 00:00:00
abstract::Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz300
更新日期:2020-02-01 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::Biallelic loss-of-function mutations in the RNA-binding protein EIF4A3 cause Richieri-Costa-Pereira syndrome (RCPS), an autosomal recessive condition mainly characterized by craniofacial and limb malformations. However, the pathogenic cellular mechanisms responsible for this syndrome are entirely unknown. Here, we use...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx078
更新日期:2017-06-15 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::Genome-wide association studies and, more recently, next-generation sequencing studies have accelerated the investigation of complex human traits by providing a wealth of association data linking genetic variants to diseases and other phenotypic traits. These data promise to transform our understanding of the molecula...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/dds363
更新日期:2012-10-15 00:00:00
abstract::Multiple studies have underscored the importance of loss of tumor suppressor genes in the development of human cancer. To identify these genes, we used somatic cell hybrids in a functional assay for tumor suppression in vivo. A tumor suppressor gene in 11p15.5 was detected by transferring single human chromosomes into...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.2.239
更新日期:1996-02-01 00:00:00