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 large and varied genomic databases. There is now recognition that international collaboration between research and healthcare systems are paramount to delivering the scale of genomic data required. No single research group, institute or country will liberate our understanding, it is only through global cooperation, together with super computing power, will we truly make sense of how genotype and phenotype correlate. Whilst it is logistically possible to create computing systems that talk to each other and aggregate datasets ready to reveal novel correlations, the bottom line is that this will only happen if people (whether they be scientists, clinicians, patients, research participants, policy makers, politicians, law makers) support the principle that we should be donating, accessing and sharing our DNA data in this way. And in order to make the most sense of genomics, given the geographical and ancestral variation between us, such people are likely to be the majority of society. Within this review, a perspective is proffered on the human story that underpins genomic 'big data' access and how we are at a tipping point as a society-we need to decide collectively, are we in? and if so, what needs to be in place to protect us? or are we out?
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Middleton Adoi
10.1093/hmg/ddy084subject
Has Abstractpub_date
2018-05-01 00:00:00pages
R8-R13issue
R1eissn
0964-6906issn
1460-2083pii
4924415journal_volume
27pub_type
杂志文章,评审abstract::Nicotine is thought to act on brain monoamine systems that normally mediate diverse motivational behaviors. How monoamine-related genes contribute to behavioral traits (e.g. responses to novel stimuli) comorbid with the susceptibility to nicotine addiction is still poorly understood. We examined the impact of constitu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl206
更新日期:2006-09-15 00:00:00
abstract::Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.9.1373
更新日期:1996-09-01 00:00:00
abstract::Mutations in DNAJC13 gene have been linked to familial form of Parkinson's disease (PD) with Lewy pathology. DNAJC13 is an endosome-related protein and believed to regulate endosomal membrane trafficking. However, the mechanistic link between DNAJC13 mutation and α-synuclein (αSYN) pathology toward neurodegeneration r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy003
更新日期:2018-03-01 00:00:00
abstract::Parkinson's disease (PD) is a severe neurological disorder, characterized by the progressive degeneration of the dopaminergic nigrostriatal pathway and the presence of Lewy bodies (LBs). The discovery of genes responsible for familial forms of the disease has provided insights into its pathogenesis. Mutations in the p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg159
更新日期:2003-06-15 00:00:00
abstract::In vitro fertilization (IVF), blastomere biopsy of the 6-8 cell embryo, and single cell DNA diagnosis allows couples at risk of transmitting an X-linked or autosomal disease to start a pregnancy knowing their child will not be affected. We present a quick and reliable nested PCR strategy for sex determination at the s...
journal_title:Human molecular genetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/hmg/2.8.1187
更新日期:1993-08-01 00:00:00
abstract::We have studied the dynamics of mitochondrial DNA maintenance and segregation in human cells using serial cybrid transfer of partially duplicated mitochondrial DNA, from a mitochondrial myopathy patient, to two distinct recipient cell types. The results indicate two radically different outcomes dependent upon nuclear ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.8.1251
更新日期:1997-08-01 00:00:00
abstract::Epidermolytic hyperkeratosis (EHK), (bullous congenital ichthyosiform erythroderma), is an autosomal dominant human skin disorder. Recently, we and others have described mutations in keratins 1 and 10 (K1 and K10) in patients with this disease. Structure-function models predict that these mutations would impair normal...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.12.2147
更新日期:1993-12-01 00:00:00
abstract::Familial exudative vitreoretinopathy (FEVR) belongs to a group of genetically and clinically heterogeneous disorders in retinal vascular development. To date, in approximately 50% of patients with FEVR, pathogenic mutations have been detected in FZD4, LRP5, TSPAN12, NDP and ZNF408. In this study, we identified two het...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw041
更新日期:2016-04-15 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::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
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq434
更新日期:2011-01-01 00:00:00
abstract::In order to characterize the dynamics of CTG repeat instability in somatic and germline tissue from myotonic dystrophy (DM) males we have used small pool polymerase chain reaction (PCR) in a detailed quantitative analysis of repeat length variation. We demonstrate that the heterogeneous smear of CTG repeats observed i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.1.1
更新日期:1995-01-01 00:00:00
abstract::A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial group...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.5.899
更新日期:1999-05-01 00:00:00
abstract::The brain-specific miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 domain is implicated in several aspects of brain development and function, particularly in fine-tuning the dendritic outgrowth and spine remodelling of hippocampal neurons. Whether it might influence behaviour and memory-related processes has n...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv510
更新日期:2016-02-15 00:00:00
abstract::PTEN-induced putative kinase 1 (PINK1) and Parkin act in a common pathway to regulate mitochondrial dynamics, the involvement of which in the pathogenesis of Parkinson's disease (PD) is increasingly being appreciated. However, how the PINK1/Parkin pathway influences mitochondrial function is not well understood, and t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr235
更新日期:2011-08-15 00:00:00
abstract::We examined the imprinting status of the insulin-like growth factor II gene (IGF2) in a series of 20 human breast disease samples to determine if disrupted imprinting (as evidenced by biallelic expression), was a demonstrable mechanism of altered gene expression. These samples included benign (n = 7) and malignant bre...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.8.1123
更新日期:1996-08-01 00:00:00
abstract::Long non-coding RNAs (lncRNAs) are post-transcriptional and epigenetic regulators, whose implication in neurodegenerative and autoimmune diseases remains poorly understood. We analyzed publicly available microarray data sets to identify dysregulated lncRNAs in multiple sclerosis (MS), a neuroinflammatory autoimmune di...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy438
更新日期:2019-05-01 00:00:00
abstract::Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected s...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds477
更新日期:2013-02-15 00:00:00
abstract::Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen-branching enzyme (GBE). The diagnostic hallmark of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variab...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv385
更新日期:2015-12-01 00:00:00
abstract::Filamin B (FLNB) is a cytoplasmic protein that regulates the cytoskeletal network by cross-linking actin, linking cell membrane to the cytoskeleton and regulating intracellular signaling pathways responsible for skeletal development (Stossel, T.P., Condeelis, J., Cooley, L., Hartwig, J.H., Noegel, A., Schleicher, M. a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm114
更新日期:2007-07-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/9.16.2443
更新日期:2000-10-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn400
更新日期:2009-02-15 00:00:00
abstract::Proper localization and anchorage of nuclei within skeletal muscle is critical for cellular function. Alterations in nuclear anchoring proteins modify a number of cellular functions including mechanotransduction, nuclear localization, chromatin positioning/compaction and overall organ function. In skeletal muscle, nes...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu310
更新日期:2014-11-15 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::Release of amyloid beta (Abeta) from the amyloid precursor protein (APP) requires cleavages by beta- and gamma-secretases and plays a crucial role in Alzheimer's disease (AD) pathogenesis. Missense mutations in the APP gene causing familial AD are clustered around the beta-, alpha- and particular gamma-secretase cleav...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2001-08-01 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::Mutations in transforming growth factor beta (TGFβ) receptor type II (TGFBR2) cause Loeys-Dietz syndrome, characterized by craniofacial and cardiovascular abnormalities. Mice with a deletion of Tgfbr2 in cranial neural crest cells (Tgfbr2(fl/fl);Wnt1-Cre mice) develop cleft palate as the result of abnormal TGFβ signal...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt410
更新日期:2014-01-01 00:00:00
abstract::Deletion of the distal short arm of chromosome 9 (9p) has been reported in a number of cases to be associated with gonadal dysgenesis and XY sex reversal, suggesting that this region contains one or more genes required in two copies for normal testis development. Recent studies have greatly narrowed the interval conta...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.6.989
更新日期:1999-06-01 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::Mutations of the thyroid hormone receptor α gene (THRA) cause hypothyroidism in patients with growth and developmental retardation, and skeletal dysplasia. Genetic evidence indicates that the dominant negative activity of TRα1 mutants underlies pathological manifestations. Using a mouse model of hypothyroidism caused ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt660
更新日期:2014-05-15 00:00:00