The 1000 Genomes Project: new opportunities for research and social challenges

Via, Marc; Gignoux, Christopher R.; Burchard, Esteban G.

doi:10.1186/gm124

Cited by 129 publications

(103 citation statements)

References 2 publications

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“…Third, inbred unions are more prevalent in non-Western societies, such as North Africa, the Middle East, and Central Asia (Bittles 2001). These ethnic groups tend to be less represented in variation repositories (Carlson et al 2003;Via et al 2010), reducing the power of eliminating common polymorphisms.…”

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confidence: 99%

Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis

Erlich¹,

Edvardson²,

Hodges³

et al. 2011

Genome Res.

177

121

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Whole exome sequencing has become a pivotal methodology for rapid and cost-effective detection of pathogenic variations in Mendelian disorders. A major challenge of this approach is determining the causative mutation from a substantial number of bystander variations that do not play any role in the disease etiology. Current strategies to analyze variations have mainly relied on genetic and functional arguments such as mode of inheritance, conservation, and loss of function prediction. Here, we demonstrate that disease-network analysis provides an additional layer of information to stratify variations even in the presence of incomplete sequencing coverage, a known limitation of exome sequencing. We studied a case of Hereditary Spastic Paraparesis (HSP) in a single inbred Palestinian family. HSP is a group of neuropathological disorders that are characterized by abnormal gait and spasticity of the lower limbs. Forty-five loci have been associated with HSP and lesions in 20 genes have been documented to induce the disorder. We used whole exome sequencing and homozygosity mapping to create a list of possible candidates. After exhausting the genetic and functional arguments, we stratified the remaining candidates according to their similarity to the previously known disease genes. Our analysis implicated the causative mutation in the motor domain of KIF1A, a gene that has not yet associated with HSP, which functions in anterograde axonal transportation. Our strategy can be useful for a large class of disorders that are characterized by locus heterogeneity, particularly when studying disorders in single families.[Supplemental material is available for this article. The sequencing and genotyping data from this study have been submitted to the NCBI dbGaP (http://www.ncbi.nlm.nih.gov/gap) and at http://cancan.cshl.edu/hsp/.]Whole exome sequencing has ushered in a renaissance in identifying pathogenic variations in monogenic diseases. The approach enables a rapid and cost-effective detection from a small number of individuals, and has proved useful for a wide range of clinical settings (Choi et al.

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mentioning

confidence: 99%

Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis

Erlich¹,

Edvardson²,

Hodges³

et al. 2011

Genome Res.

177

121

View full text Add to dashboard Cite

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“…The genotype data were downloaded from TCGA portal and used as our gold standards. To test the SNP callers' performance without using SNP arrays as the benchmark, we used data from one Yoruba individual (1,000 genomes accession code: NA19240) with high coverage MAQ alignment data of chromosome 21(39 Â ) and 22(40 Â ) generated by the pilot 2 phase of 1,000 Genomes Project 28 . To compare the performance of FaSD on pooled samples with the performance of GATK and Bcftools, we used the publically available sequencing data from 40 CEU individuals in the pilot 1 phase of 1,000 Genomes Project.…”

Section: Methodsmentioning

confidence: 99%

A fast and accurate SNP detection algorithm for next-generation sequencing data

Wang

et al. 2012

Nat Commun

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Various methods have been developed for calling single-nucleotide polymorphisms from next-generation sequencing data. However, for satisfactory performance, most of these methods require expensive high-depth sequencing. Here, we propose a fast and accurate single-nucleotide polymorphism detection program that uses a binomial distribution-based algorithm and a mutation probability. We extensively assess this program on normal and cancer next-generation sequencing data from The Cancer Genome Atlas project and pooled data from the 1,000 Genomes Project. We also compare the performance of several stateof-the-art programs for single-nucleotide polymorphism calling and evaluate their pros and cons. We demonstrate that our program is a fast and highly accurate single-nucleotide polymorphism detection method, particularly when the sequence depth is low. The program can finish single-nucleotide polymorphism calling within four hours for 10-fold human genome next-generation sequencing data (30 gigabases) on a standard desktop computer.

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“…We use genome data provided by the 1000 Genomes Project as evaluation data set [21]. For our evaluation, we use the aligned sequences of one human sample called HG00096 that are aligned to human chromosome 1.…”

Section: A Experimental Setupmentioning

confidence: 99%

Toward Efficient Variant Calling Inside Main-Memory Database Systems

Dorok

Breß

Saake

2014

2014 25th International Workshop on Database and Expert Systems Applications

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Abstract-Mutations in genomes indicate predisposition for diseases or effects on efficacy of drugs. A variant calling algorithm determines possible mutations in sample genomes. Afterwards, scientists have to decide about the impact of these mutations. Certainly, many different variant calling algorithms exist that generate different outputs due to different sequence alignments as input and parameterizations of variant calling algorithms. Thus, a combination of variant calling results is necessary to provide a more complete set of mutations than single algorithm runs can provide. Therefore, a system is required that facilitates the integration and parameterization of different variant calling algorithms and processing of different sequence alignments. Moreover, against the backdrop of ever increasing amounts of available genome sequencing data, such a system must provide matured database management capabilities to enable flexible and efficient analyses while keeping data consistent. In this paper, we present a first approach to integrate variant calling into a main-memory database management system that allows for calling variants via SQL.

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The 1000 Genomes Project: new opportunities for research and social challenges

Cited by 129 publications

References 2 publications

Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis

Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis

A fast and accurate SNP detection algorithm for next-generation sequencing data

Toward Efficient Variant Calling Inside Main-Memory Database Systems

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