Abstract:
:Age-related macular degeneration (AMD) is a progressive neurodegenerative disease, which affects quality of life for millions of elderly individuals worldwide. AMD is associated with a diverse spectrum of clinical phenotypes, all of which include the death of photoreceptors in the central part of the human retina (called the macula). Tremendous progress has been made in identifying genetic susceptibility variants for AMD. Variants at chromosome 1q32 (in the region of CFH) and 10q26 (LOC387715/ARMS2) account for a large part of the genetic risk to AMD and have been validated in numerous studies. In addition, susceptibility variants at other loci, several as yet unidentified, make substantial cumulative contribution to genetic risk for AMD; among these, multiple studies support the role of variants in APOE and C2/BF genes. Genome-wide association and re-sequencing projects, together with gene-environment interaction studies, are expected to further define the causal relationships that connect genetic variants to AMD pathogenesis and should assist in better design of prevention and intervention.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Swaroop A,Branham KE,Chen W,Abecasis Gdoi
10.1093/hmg/ddm212subject
Has Abstractpub_date
2007-10-15 00:00:00pages
R174-82eissn
0964-6906issn
1460-2083pii
16/R2/R174journal_volume
16 Spec No. 2pub_type
杂志文章,评审abstract::Deficiencies in the complex I (CI; NADH-ubiquinone oxidoreductase) of the respiratory chain are frequent causes of mitochondrial diseases and have been associated with other neurodegenerative disorders, such as Parkinson's disease. The NADH-ubiquinone oxidoreductase 1 alpha subcomplex subunit 5 (NDUFA5) is a nuclear-e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt526
更新日期:2014-03-15 00:00:00
abstract::ATRX is a chromatin remodeling protein involved in deposition of the histone variant H3.3 at telomeres and pericentromeric heterochromatin. It also influences the expression level of specific genes; however, deposition of H3.3 at transcribed genes is currently thought to occur independently of ATRX. We focused on a se...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu596
更新日期:2015-04-01 00:00:00
abstract::Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq556
更新日期:2011-03-15 00:00:00
abstract::Schizophrenia may arise from subtle abnormalities in brain development due to alterations in the functions of candidate susceptibility genes such as Disrupted-in-schizophrenia 1 (DISC1) and Neuregulin 1 (NRG1). To provide novel insights into the functions of DISC1 in brain development, we mapped the expression of zebr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn361
更新日期:2009-02-01 00:00:00
abstract::We, amongst others, have shown that CC homozygosity at the -22C>T promoter polymorphism in presenilin 1 (PSEN1) is associated with increased risk for Alzheimer's disease (AD). Also, studies in AD brains suggested that CC homozygosity increased the risk for AD by increasing the Abeta load. We characterized the PSEN1 pr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg098
更新日期:2003-04-15 00:00:00
abstract::Serum total immunoglobulin E (IgE) is a critical intermediate phenotype of allergic diseases. Although total IgE exhibits sexual dimorphism in humans (with males demonstrating higher IgE than females), the molecular basis of this difference is unknown. A genome-wide scan of 380 short-tandem repeat (STR) markers was pe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl447
更新日期:2007-02-01 00:00:00
abstract::Congenital heart defects affect at least 0.8% of newborn children and are a major cause of lethality prior to birth. Malformations of the arterial pole are particularly frequent. The myocardium at the base of the pulmonary trunk and aorta and the arterial tree associated with these great arteries are derived from spla...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu232
更新日期:2014-10-01 00:00:00
abstract::To understand the cause of Parkinson's disease (PD), it is important to determine the functional interactions between factors linked to the disease. Parkin is associated with autosomal recessive early-onset PD, and controls the transcription of PGC-1α, a master regulator of mitochondrial biogenesis. These two factors ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw418
更新日期:2017-02-01 00:00:00
abstract::Three distinct regions, designated AZFa, b and c from proximal to distal Yq, are required for normal spermato-genesis in humans. Deletions involving AZFa (deletion interval 5C/D) seem to occur less frequently in infertile men and to be associated with a more severe testicular phenotype, with almost complete absence of...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.8.1161
更新日期:2000-05-01 00:00:00
abstract::A relationship between fragile sites, specific genomic regions visible as gaps or breaks on cultivated chromosomes, and human disease has been proposed many years ago. Evidence for a role of the ubiquitously expressed common fragile sites characterized by peculiar genome architecture in cancer has been accumulated ove...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddm136
更新日期:2007-10-15 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::The lifetime accumulation of low-abundance, somatic mtDNA re-arrangements (sublimons) has been proposed as a potential contributor to aging, and also to diseases such as cardiomyopathy or coronary heart disease. Tissue-specific sublimons, varying in abundance by three orders of magnitude between individuals, have rece...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.3.317
更新日期:2002-02-01 00:00:00
abstract::Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor homology domain repeat A of the low-density lipoprotein receptor (LDLR) at the cell surface and disrupts recycling of the internalized LDLR. As a consequence, the LDLR is rerouted to the lysosomes for degradation. Although PCSK9...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr578
更新日期:2012-03-15 00:00:00
abstract::The defective gene responsible for the recessively inherited immunodeficiency X-linked agammaglobulinemia (XLA) has been shown to encode a cytoplasmic protein tyrosine kinase of the Src family designated Btk (Bruton's tyrosine kinase). To facilitate the search for germline mutations of the Btk gene, we have characteri...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.10.1743
更新日期:1994-10-01 00:00:00
abstract::Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin. Gene replacement therapy is a promising strategy for treatment of the disease; however, the effectiveness and safety of gi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu556
更新日期:2015-03-01 00:00:00
abstract::Potocki-Lupski syndrome (PTLS; MIM #610883), characterized by neurobehavioral abnormalities, intellectual disability and congenital anomalies, is caused by a 3.7-Mb duplication in 17p11.2. Neurobehavioral studies determined that ∼70-90% of PTLS subjects tested positive for autism or autism spectrum disorder (ASD). We ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds124
更新日期:2012-07-15 00:00:00
abstract::The members of the huntingtin-interacting protein-1 (HIP1) family, HIP1 and HIP1-related (HIP1r), are multi-domain proteins that interact with inositol lipids, clathrin and actin. HIP1 is over-expressed in a variety of cancers and both HIP1 and HIP1r prolong the half-life of multiple growth factor receptors. To better...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm076
更新日期:2007-06-01 00:00:00
abstract::Mutations in the presenilin 1 ( PSEN1 ) gene have been implicated in 18-50% of autosomal dominant cases with early-onset Alzheimer's disease (EOAD). Also, PSEN1 has been suggested as a potential risk gene in late-onset AD cases. We recently showed genetic association in a population-based study of EOAD, pointing to th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.3.325
更新日期:2000-02-12 00:00:00
abstract::Gene silencing through aberrant CpG island methylation is a frequent epigenetic defect in hepatocellular carcinoma (HCC). However, nothing is known as yet whether aberrant hypermethylation occurs already in non-neoplastic liver cells from patients with hereditary haemochromatosis who have a clearly elevated risk for d...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm082
更新日期:2007-06-01 00:00:00
abstract::Spinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder that results from the expansion of a cryptic CAG repeat within the exon 1 of the SCA2 gene. The CAG repeat in normal individuals varies in length from 14 to 31 repeats and is frequently interrupted by one or more CAA triplets, whereas ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.21.2437
更新日期:2001-10-01 00:00:00
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 re...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn397
更新日期:2009-02-15 00:00:00
abstract::Positional cloning has previously resulted in the identification of a gene which is disrupted by deletions in patients with the classic choroideremia (CHM) phenotype. More subtle mutations had been identified in 4 exons of the 3' portion but not elsewhere in the CHM gene. We have now isolated and characterized the com...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.7.1041
更新日期:1994-07-01 00:00:00
abstract::Despite the immense significance retrotransposons have had for genome evolution much about their biology is unknown, including the processes of forming their ribonucleoprotein (RNP) particles and transporting them about the cell. Suppression of retrotransposon expression, together with the presence of retrotransposon ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq048
更新日期:2010-05-01 00:00:00
abstract::Mutations that affect calcium homeostasis (Ca(2+)) in rod photoreceptors are linked to retinal degeneration and visual disorders such as retinitis pigmentosa and congenital stationary night blindness (CSNB). It is thought that the concentration of Ca(2+) in rod outer segments is controlled by a dynamic balance between...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv319
更新日期:2015-10-15 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::Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Here, we provide evidence supporting the hypothesis that somatic increases of mutation length play a role in the progressive nature and cell-selective aspects of HD pathogenesis. Results f...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm054
更新日期:2007-05-15 00:00:00
abstract::Hearing loss is the most common sensory deficit in humans. We show that a point mutation in DCDC2 (DCDC2a), a member of doublecortin domain-containing protein superfamily, causes non-syndromic recessive deafness DFNB66 in a Tunisian family. Using immunofluorescence on rat inner ear neuroepithelia, DCDC2a was found to ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv009
更新日期:2015-05-01 00:00:00
abstract::An increased rate of de novo copy number variants (CNVs) has been found in schizophrenia (SZ), autism and developmental delay. An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We us...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu379
更新日期:2014-12-15 00:00:00
abstract::Adoptively transferred antigen-specific T cells that recognize tumor antigens through their native receptors have many potential benefits as treatment for virus-associated diseases and malignancies, due to their ability to selectively recognize tumor antigens, expand and persist to provide long-term protection. Infusi...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddv270
更新日期:2015-10-15 00:00:00
abstract::Ataxia-telangiectasia (A-T) is a multisystem, cancer-predisposing genetic disorder caused by deficiency of the ATM protein. To dissect the A-T phenotype, we augmented specific features of the human disease by generating mouse strains that combine Atm deficiency with dysfunction of other proteins. Increasing oxidative ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi324
更新日期:2005-10-01 00:00:00