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variants, genes, pathogenic, recessive, pubmed, reported, clinvar, individuals, article, autosomal, disease, variant, google, scholar, study, number, sequencing, additional, deleterious, average, central, data, file, clinical, predicted, analysis, sample, individual, cas, carrier, observed, genome, list, exome, frequency, mendelian, human, gene, risk, aric, nonsynonymous, studies, genet, findings, ethnic, med, populations, nonsense, acmg, groups,

Topics {✒️}

int/genomics/public/geneticdiseases/en/index2 cas  google scholar gov/sites/default/files/finalanticipatecommunicate_pcsbi_0 escape nonsense-mediated decay x-linked disease gene hgmd-disease-causing mutation x-linked recessive disorders x-linked recessive genes article download pdf x-linked disease genes formal cost-benefit analyses paraffin-embedded tumor samples baylor-johns hopkins center �disease-causing mutation” genome-wide association studies population-based brca1/2 testing large-scale genomic studies autosomal recessive gene disease-causing alleles presumed nmd-escaping regions support vector machine deleterious genetic variation recessive disease gene full access recessive carrier status gene-specific function prediction privacy choices/manage cookies autosomal recessive disorders autosomal recessive conditions autosomal recessive genes exome-based diagnoses reid jg online mendelian inheritance comprehensive mutation repository recessive disease genes large multiethnic sample recessive carrier alleles national science center identify heterozygous alleles hgmd-dm variants showed multiple case–control studies rare nonsynonymous variants blood institute contracts related subjects predicted deleterious variant large-scale initiative presumed mendelian disease false positive rate rare unclassified variants routine genome testing

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         headline:Secondary findings and carrier test frequencies in a large multiethnic sample
         description:Besides its growing importance in clinical diagnostics and understanding the genetic basis of Mendelian and complex diseases, whole exome sequencing (WES) is a rich source of additional information of potential clinical utility for physicians, patients and their families. We analyzed the frequency and nature of single nucleotide variants (SNVs) considered secondary findings and recessive disease allele carrier status in the exomes of 8554 individuals from a large, randomly sampled cohort study and 2514 patients from a study of presumed Mendelian disease having undergone WES. We used the same sequencing platform and data processing pipeline to analyze all samples and characterized the distributions of reported pathogenic (ClinVar, Human Gene Mutation Database (HGMD)) and predicted deleterious variants in the pre-specified American College of Medical Genetics and Genomics (ACMG) secondary findings and recessive disease genes in different ethnic groups. In the 56 ACMG secondary findings genes, the average number of predicted deleterious variants per individual was 0.74, and the mean number of ClinVar reported pathogenic variants was 0.06. We observed an average of 10 deleterious and 0.78 ClinVar reported pathogenic variants per individual in 1423 autosomal recessive disease genes. By repeatedly sampling pairs of exomes, 0.5 % of the randomly generated couples were at 25 % risk of having an affected offspring for an autosomal recessive disorder based on the ClinVar variants. By investigating reported pathogenic and novel, predicted deleterious variants we estimated the lower and upper limits of the population fraction for which exome sequencing may reveal additional medically relevant information. We suggest that the observed wide range for the lower and upper limits of these frequency numbers will be gradually reduced due to improvement in classification databases and prediction algorithms.
         datePublished:2015-06-13T00:00:00Z
         dateModified:2015-06-13T00:00:00Z
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            Autosomal Recessive Disease
            Nonsynonymous Variant
            Autosomal Recessive
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            Metabolomics
            Bioinformatics
            Medicine/Public Health
            general
            Cancer Research
            Systems Biology
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      headline:Secondary findings and carrier test frequencies in a large multiethnic sample
      description:Besides its growing importance in clinical diagnostics and understanding the genetic basis of Mendelian and complex diseases, whole exome sequencing (WES) is a rich source of additional information of potential clinical utility for physicians, patients and their families. We analyzed the frequency and nature of single nucleotide variants (SNVs) considered secondary findings and recessive disease allele carrier status in the exomes of 8554 individuals from a large, randomly sampled cohort study and 2514 patients from a study of presumed Mendelian disease having undergone WES. We used the same sequencing platform and data processing pipeline to analyze all samples and characterized the distributions of reported pathogenic (ClinVar, Human Gene Mutation Database (HGMD)) and predicted deleterious variants in the pre-specified American College of Medical Genetics and Genomics (ACMG) secondary findings and recessive disease genes in different ethnic groups. In the 56 ACMG secondary findings genes, the average number of predicted deleterious variants per individual was 0.74, and the mean number of ClinVar reported pathogenic variants was 0.06. We observed an average of 10 deleterious and 0.78 ClinVar reported pathogenic variants per individual in 1423 autosomal recessive disease genes. By repeatedly sampling pairs of exomes, 0.5 % of the randomly generated couples were at 25 % risk of having an affected offspring for an autosomal recessive disorder based on the ClinVar variants. By investigating reported pathogenic and novel, predicted deleterious variants we estimated the lower and upper limits of the population fraction for which exome sequencing may reveal additional medically relevant information. We suggest that the observed wide range for the lower and upper limits of these frequency numbers will be gradually reduced due to improvement in classification databases and prediction algorithms.
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      dateModified:2015-06-13T00:00:00Z
      pageStart:1
      pageEnd:14
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      sameAs:https://doi.org/10.1186/s13073-015-0171-1
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         Autosomal Recessive Disease
         Nonsynonymous Variant
         Autosomal Recessive
         Human Gene Mutation Database
         Human Genetics
         Metabolomics
         Bioinformatics
         Medicine/Public Health
         general
         Cancer Research
         Systems Biology
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                  address:
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            name:Shalini N. Jhangiani
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      name:Donna M. Muzny
      affiliation:
            name:Baylor College of Medicine
            address:
               name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Jeffrey Staples
      affiliation:
            name:University of Texas Health Science Center at Houston
            address:
               name:Human Genetics Center, University of Texas Health Science Center at Houston, Houston, USA
               type:PostalAddress
            type:Organization
      name:Alanna C. Morrison
      affiliation:
            name:University of Texas Health Science Center at Houston
            address:
               name:Human Genetics Center, University of Texas Health Science Center at Houston, Houston, USA
               type:PostalAddress
            type:Organization
      name:Matthew N. Bainbridge
      affiliation:
            name:Baylor College of Medicine
            address:
               name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Samantha Penney
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Department of Pediatrics, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Texas Children’s Hospital
            address:
               name:Texas Children’s Hospital, Houston, USA
               type:PostalAddress
            type:Organization
      name:Amy L. McGuire
      affiliation:
            name:Baylor College of Medicine
            address:
               name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Richard A. Gibbs
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:James R. Lupski
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Pediatrics, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Texas Children’s Hospital
            address:
               name:Texas Children’s Hospital, Houston, USA
               type:PostalAddress
            type:Organization
      name:Eric Boerwinkle
      affiliation:
            name:Baylor College of Medicine
            address:
               name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:University of Texas Health Science Center at Houston
            address:
               name:Human Genetics Center, University of Texas Health Science Center at Houston, Houston, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland
      name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Human Genetics Center, University of Texas Health Science Center at Houston, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Human Genetics Center, University of Texas Health Science Center at Houston, Houston, USA
      name:Human Genetics Center, University of Texas Health Science Center at Houston, Houston, USA
      name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Department of Pediatrics, Baylor College of Medicine, Houston, USA
      name:Texas Children’s Hospital, Houston, USA
      name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Department of Pediatrics, Baylor College of Medicine, Houston, USA
      name:Texas Children’s Hospital, Houston, USA
      name:The Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Human Genetics Center, University of Texas Health Science Center at Houston, Houston, USA

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