Abstract:
:First- and second-generation sequencing technologies have led the way in revolutionizing the field of genomics and beyond, motivating an astonishing number of scientific advances, including enabling a more complete understanding of whole genome sequences and the information encoded therein, a more complete characterization of the methylome and transcriptome and a better understanding of interactions between proteins and DNA. Nevertheless, there are sequencing applications and aspects of genome biology that are presently beyond the reach of current sequencing technologies, leaving fertile ground for additional innovation in this space. In this review, we describe a new generation of single-molecule sequencing technologies (third-generation sequencing) that is emerging to fill this space, with the potential for dramatically longer read lengths, shorter time to result and lower overall cost.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Schadt EE,Turner S,Kasarskis Adoi
10.1093/hmg/ddq416subject
Has Abstractpub_date
2010-10-15 00:00:00pages
R227-40issue
R2eissn
0964-6906issn
1460-2083pii
ddq416journal_volume
19pub_type
杂志文章,评审abstract::Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate and myelination. Here we ask if modulating NRG1 type III le...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy420
更新日期:2019-04-15 00:00:00
abstract::Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone diseas...
journal_title:Human molecular genetics
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abstract::Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein. Full-length huntingtin is thought to be a predominant HEAT repeat alpha-solenoid, implying a role as a facilitator of macromolecular complexes. Here we have investigated huntingtin's domain structure an...
journal_title:Human molecular genetics
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doi:10.1093/hmg/ddp524
更新日期:2010-02-15 00:00:00
abstract::Huntington's disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine (polyQ) tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu522
更新日期:2015-02-15 00:00:00
abstract::Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease. A major path...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx214
更新日期:2017-09-01 00:00:00
abstract::The most common form of hereditary haemochromatosis is an adult-onset condition usually associated with the HFE C282Y/C282Y genotype. The phenotypic expression of this genotype is heterogeneous and depends on a complex interplay of genetic and non-genetic factors. The aim of the present study was to determine if mutat...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh206
更新日期:2004-09-01 00:00:00
abstract::We have cloned, sequenced and annotated segments of DNA spanning the mouse, chicken and pufferfish alpha globin gene clusters and compared them with the corresponding region in man. This has defined a small segment ( approximately 135-155 kb) of synteny and conserved gene order, which may contain all of the elements r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.4.371
更新日期:2001-02-15 00:00:00
abstract::Mutations in PARK8, encoding leucine-rich repeat kinase 2 (LRRK2), are a frequent cause of Parkinson's disease (PD). Nonetheless, the physiological role of LRRK2 remains unclear. Here, we demonstrate that LRRK2 participates in canonical Wnt signaling as a scaffold. LRRK2 interacts with key Wnt signaling proteins of th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds342
更新日期:2012-11-15 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::BRCA1 and BRCA2 germline mutations account for <5% of breast cancer cases. Less penetrant breast cancer susceptibility genes are likely to exist. Earlier studies have suggested involvement of the HLA region. The HLA region was genotyped with 24 microsatellite markers and markers for two single nucleotide polymorphisms...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2003-09-15 00:00:00
abstract::The APOE epsilon4 allele is a strong genetic susceptibility factor for Alzheimer's disease. Interaction with other biological factors may modulate the effect of the apoE isoforms. However, previous work suggested that other genetic variability within the APOE locus, influencing the effect of the epsilon4 allele, may e...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.12.2151
更新日期:1997-11-01 00:00:00
abstract::In model organisms, over 2,000 genes have been shown to modulate aging, the collection of which we call the ‘gerontome’. Although some individual aging-related genes have been the subject of intense scrutiny, their analysis as a whole has been limited. In particular, the genetic interaction of aging and age-related pa...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw307
更新日期:2016-11-01 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::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::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::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
abstract::Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could redu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz086
更新日期:2019-08-15 00:00:00
abstract::Osteoarthritis (OA) is a common, painful and debilitating disease of articulating joints resulting from the age-associated loss of cartilage. Well-powered genetic studies have identified a number of DNA polymorphisms that are associated with OA susceptibility. Like most complex trait loci, these OA loci are thought to...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv433
更新日期:2015-12-20 00:00:00
abstract::Dominant mutations in the gene encoding the ubiquitously-expressed splicing factor PRPF31 cause retinitis pigmentosa, a form of hereditary retinal degeneration, with reduced penetrance. We and others have previously shown that penetrance is tightly correlated with PRPF31 expression, as lymphoblastoid cell lines (LCLs)...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn212
更新日期:2008-10-15 00:00:00
abstract::Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a life-threatening hypermetabolic crisis triggered by commonly-used inhalation anaesthetics and depolarizing muscle relaxants. Defects in the ryanodine receptor (RYR1) protein have been proposed to under...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.7.863
更新日期:1993-07-01 00:00:00
abstract::The DTNBP1 gene, encoding dysbindin, is now generally considered to be a susceptibility gene for schizophrenia. However, the confidence with which this hypothesis can be held has to be tempered by the poor reproducibility between studies in terms of the exact nature of the associated haplotypes, by the failure so far ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi199
更新日期:2005-07-15 00:00:00
abstract::Nephropathic cystinosis, a lysosomal storage disease caused by mutations in the CTNS gene encoding the lysosomal cystine transporter cystinosin, is characterized by generalized proximal tubule (PT) dysfunction that progresses, if untreated, to end-stage renal disease. The pathogenesis of defective PT cellular transpor...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt617
更新日期:2014-05-01 00:00:00
abstract::Neurofibromas are common tumors found in neurofibromatosis type 1 (NF1) patients. These complex tumors are composed of Schwann cells, mast cells, fibroblasts and perineurial cells embedded in collagen that provide a lattice for tumor invasion. Genetic studies demonstrate that in neurofibromas, nullizygous loss of Nf1 ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl165
更新日期:2006-08-15 00:00:00
abstract::The gene B lymphocyte kinase (BLK) is associated with rheumatoid arthritis, systemic lupus erythematosus and several other autoimmune disorders. The disease risk haplotype is known to be associated with reduced expression of BLK mRNA transcript in human B cell lines; however, little is known about cis-regulation of BL...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds220
更新日期:2012-09-01 00:00:00
abstract::We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a min...
journal_title:Human molecular genetics
pub_type: 杂志文章,多中心研究
doi:10.1093/hmg/ddt403
更新日期:2014-01-01 00:00:00
abstract::CUL4A and CUL4B are closely related cullin family members and can each assemble a Cullin-RING E3 ligase complex (CRL) and participate in a variety of biological processes. While the CRLs formed by the two cullin members may have common targets, the two appeared to have very different consequences when mutated or disru...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu503
更新日期:2015-02-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is among the most common monogenic disorders mainly associated with PKD1/PC1 mutations. We show herein that renal regulation in Pc1 dosage-reduced and -increased mouse models converge toward stimulation of c-Myc expression along with β-catenin, delineating c-Myc as ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy379
更新日期:2019-03-01 00:00:00
abstract::Homozygous inv mice lack a functional inversin protein and exhibit situs inversus plus severe cystic changes in the kidney and pancreas. Although the inversin sequence has provided few clues to its function, we and others have previously identified calmodulin as a binding partner. We now provide evidence that inversin...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.26.3345
更新日期:2002-12-15 00:00:00
abstract::We investigated the population differences in patterns of single nucleotide polymorphisms (SNPs) for a 400 kb olfactory receptor (OR) gene cluster on human chromosome 17p13.3. Samples were drawn from 35 individuals, of four different ethnogeographical origins: Pygmies, Bedouins, Yemenite Jews and Ashkenazi Jews. Of th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.12.1381
更新日期:2002-06-01 00:00:00
abstract::Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2-/-). Although...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq453
更新日期:2011-01-01 00:00:00