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Keywords {🔍}

variants, allele, pilot, data, frequency, exon, sites, file, call, additional, snp, low, figure, variant, coverage, population, table, calls, sequencing, pubmed, article, samples, populations, indel, indels, set, calling, sets, quality, snps, rare, human, methods, coding, sequence, illumina, regions, reads, analysis, project, google, scholar, functional, base, validation, genome, read, rate, cas, capture,

Topics {✒️}

gov/1000genomes/ftp/pilot_data/release/2010_07/exon/] hernandez article download pdf genome-wide association scans age-related macular degeneration bc-specific/bi-specific sets article number r84 high transition/transversion ratio main data-related reason agilent microarray-based method full size image high ts/tv ratio genome-wide association study recent technical developments population-specific call sets low-frequency coding variation bi-specific call sets broad institute employed illumina ga-ii sequencers single-nucleotide polymorphism discovery high-throughput data collection population-specific sample sets 76-bp paired-end reads paired-end 37-bp reads identify disease-causing alleles bcm-hgsc call set gutenkunst rn related pilot programs indel calling procedure exon pilot project exon pilot snp the1000 genomes project snp calling algorithm 454 flx/titanium platform privacy choices/manage cookies human genetic variation indel size analysis atlas-indel2 pipeline specific dna sequences chris tyler-smith rare variants constitute full access human genome variation indel call set exon pilot data snp calling procedure exon-specific nature rare genetic variation trio sequencing pilot exon pilot dataset snp calling procedures

Questions {❓}

• Antonarakis SE, Chakravarti A, Cohen JC, Hardy J: Mendelian disorders and multifactorial traits: the big divide or one for all?
• Pritchard JK: Are rare variants responsible for susceptibility to complex diseases?

Schema {🗺️}

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         headline:The functional spectrum of low-frequency coding variation
         description:Rare coding variants constitute an important class of human genetic variation, but are underrepresented in current databases that are based on small population samples. Recent studies show that variants altering amino acid sequence and protein function are enriched at low variant allele frequency, 2 to 5%, but because of insufficient sample size it is not clear if the same trend holds for rare variants below 1% allele frequency. The 1000 Genomes Exon Pilot Project has collected deep-coverage exon-capture data in roughly 1,000 human genes, for nearly 700 samples. Although medical whole-exome projects are currently afoot, this is still the deepest reported sampling of a large number of human genes with next-generation technologies. According to the goals of the 1000 Genomes Project, we created effective informatics pipelines to process and analyze the data, and discovered 12,758 exonic SNPs, 70% of them novel, and 74% below 1% allele frequency in the seven population samples we examined. Our analysis confirms that coding variants below 1% allele frequency show increased population-specificity and are enriched for functional variants. This study represents a large step toward detecting and interpreting low frequency coding variation, clearly lays out technical steps for effective analysis of DNA capture data, and articulates functional and population properties of this important class of genetic variation.
         datePublished:2011-09-14T00:00:00Z
         dateModified:2011-09-14T00:00:00Z
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            Broad Institute
            Human Gene Mutation Database
            INDEL Calling
            INDEL Call
            Animal Genetics and Genomics
            Human Genetics
            Plant Genetics and Genomics
            Microbial Genetics and Genomics
            Bioinformatics
            Evolutionary Biology
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      headline:The functional spectrum of low-frequency coding variation
      description:Rare coding variants constitute an important class of human genetic variation, but are underrepresented in current databases that are based on small population samples. Recent studies show that variants altering amino acid sequence and protein function are enriched at low variant allele frequency, 2 to 5%, but because of insufficient sample size it is not clear if the same trend holds for rare variants below 1% allele frequency. The 1000 Genomes Exon Pilot Project has collected deep-coverage exon-capture data in roughly 1,000 human genes, for nearly 700 samples. Although medical whole-exome projects are currently afoot, this is still the deepest reported sampling of a large number of human genes with next-generation technologies. According to the goals of the 1000 Genomes Project, we created effective informatics pipelines to process and analyze the data, and discovered 12,758 exonic SNPs, 70% of them novel, and 74% below 1% allele frequency in the seven population samples we examined. Our analysis confirms that coding variants below 1% allele frequency show increased population-specificity and are enriched for functional variants. This study represents a large step toward detecting and interpreting low frequency coding variation, clearly lays out technical steps for effective analysis of DNA capture data, and articulates functional and population properties of this important class of genetic variation.
      datePublished:2011-09-14T00:00:00Z
      dateModified:2011-09-14T00:00:00Z
      pageStart:1
      pageEnd:17
      license:http://creativecommons.org/licenses/by/2.0/
      sameAs:https://doi.org/10.1186/gb-2011-12-9-r84
      keywords:
         Boston College
         Broad Institute
         Human Gene Mutation Database
         INDEL Calling
         INDEL Call
         Animal Genetics and Genomics
         Human Genetics
         Plant Genetics and Genomics
         Microbial Genetics and Genomics
         Bioinformatics
         Evolutionary Biology
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      affiliation:
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