Results 1 - 10
of
14
Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet.
, 2010
"... ..."
Small insertions and deletions (INDELs) in human genomes.Hum
- Mol. Genet
, 2010
"... In this review, we focus on progress that has been made with detecting small insertions and deletions (INDELs) in human genomes. Over the past decade, several million small INDELs have been discovered in human populations and personal genomes. The amount of genetic variation that is caused by these ..."
Abstract
-
Cited by 9 (0 self)
- Add to MetaCart
(Show Context)
In this review, we focus on progress that has been made with detecting small insertions and deletions (INDELs) in human genomes. Over the past decade, several million small INDELs have been discovered in human populations and personal genomes. The amount of genetic variation that is caused by these small INDELs is substantial. The number of INDELs in human genomes is second only to the number of single nucleotide polymorphisms (SNPs), and, in terms of base pairs of variation, INDELs cause similar levels of variation as SNPs. Many of these INDELs map to functionally important sites within human genes, and thus, are likely to influence human traits and diseases. Therefore, small INDEL variation will play a prominent role in personalized medicine.
Loss-of-function variants in the genomes of healthy humans
- Hum Mol Genet
"... Genetic variants predicted to seriously disrupt the function of human protein-coding genes—so-called loss-of-function (LOF) variants—have traditionally been viewed in the context of severe Mendelian disease. However, recent large-scale sequencing and genotyping projects have revealed a surprisingly ..."
Abstract
-
Cited by 9 (0 self)
- Add to MetaCart
(Show Context)
Genetic variants predicted to seriously disrupt the function of human protein-coding genes—so-called loss-of-function (LOF) variants—have traditionally been viewed in the context of severe Mendelian disease. However, recent large-scale sequencing and genotyping projects have revealed a surprisingly large number of these variants in the genomes of apparently healthy individuals—at least 100 per genome, includ-ing more than 30 in a homozygous state—suggesting a previously unappreciated level of variation in func-tional gene content between humans. These variants are mostly found at low frequency, suggesting that they are enriched for mildly deleterious polymorphisms suppressed by negative natural selection, and thus represent an attractive set of candidate variants for complex disease susceptibility. However, they are also enriched for sequencing and annotation artefacts, so overall present serious challenges for clinical sequencing projects seeking to identify severe disease genes amidst the ‘noise ’ of technical error and benign genetic polymorphism. Systematic, high-quality catalogues of LOF variants present in the genomes of healthy individuals, built from the output of large-scale sequencing studies such as the 1000 Genomes Project, will help to distinguish between benign and disease-causing LOF variants, and will provide valuable resources for clinical genomics.
Genetics of neurodegenerative diseases: insights from high-throughput resequencing
- Hum Mol Genet 2010; 19:R65-70. [PMID: 20413655
"... During the past three decades, we have witnessed remarkable advances in our understanding of the molecular etiologies of hereditary neurodegenerative diseases, which have been accomplished by ‘positional cloning’ strategies. The discoveries of the causative genes for hereditary neurodegenerative dis ..."
Abstract
-
Cited by 8 (0 self)
- Add to MetaCart
During the past three decades, we have witnessed remarkable advances in our understanding of the molecular etiologies of hereditary neurodegenerative diseases, which have been accomplished by ‘positional cloning’ strategies. The discoveries of the causative genes for hereditary neurodegenerative diseases accelerated not only the studies on the pathophysiologic mechanisms of diseases, but also the studies for the development of disease-modifying therapies. Genome-wide association studies (GWAS) based on the ‘common disease– common variants hypothesis ’ are currently undertaken to elucidate disease-relevant alleles. Although GWAS have successfully revealed numerous susceptibility genes for neurodegenerative diseases, odds ratios associated with risk alleles are generally low and account for only a small proportion of estimated heritability. Recent studies have revealed that the effect sizes of the disease-relevant alleles that are identified based on comprehensive resequencing of large data sets of Parkinson disease are substantially larger than those identified by GWAS. These findings strongly argue for the role of the ‘common disease–multiple rare variants hypothesis ’ in sporadic neurodegenerative diseases. Given the rapidly improving technologies of next-generation sequencing next-generation sequencing (NGS), we expect that NGS will eventually enable us to identify all the variants in an individual’s personal genome, in particular, clinically relevant alleles. Beyond this, whole genome resequencing is expected to bring a paradigm shift in clinical practice, where clinical practice including diagnosis and decision-making for appropriate therapeutic procedures is based on the ‘personal genome’. The personal genome era is expected to be realized in the near future, and society needs to prepare for this new era.
The HuRef Browser: a web resource for individual human genomics
- Nucl. Acids Res
, 2009
"... human genomics ..."
(Show Context)
Exploring the potential relevance of humanspecific genes to complex disease
- Hum. Genomics
, 2011
"... Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specif ..."
Abstract
-
Cited by 5 (0 self)
- Add to MetaCart
Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database
Shoji Tsuji
, 2010
"... This is an Open Access article distributed under the terms of the Creative Commons Attribution ..."
Abstract
- Add to MetaCart
This is an Open Access article distributed under the terms of the Creative Commons Attribution
