Expanded carrier screening for inherited genetic disease using exome and genome sequencing.

The goal of this study was to assess the feasibility of using exome (ES) and genome sequencing (GS) in guiding preconception genetic screening (PCGS) for couples who are planning to conceive by creating a workflow for identifying risk alleles for autosomal recessive (AR) and X‐linked (XL) disorders...

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Publicado en:Journal of Genetic Counseling Vol. 34; no. 2; pp. 1 - 8
Autores principales: Belnap, N., Ramsey, K., Abraham, A., Ryan, A., Rangasamy, S., Bonfitto, A., Naymik, M., Huentelman, M., Strom, S., Perry, D., Subramaniam, A., Grody, W. W., Szelinger, S., Narayanan, V.
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell Apr2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Apr2025
      vid: 34
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1002/jgc4.1964
        184767452
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        atl: Expanded carrier screening for inherited genetic disease using exome and genome sequencing.
      aug:
        au:
          Belnap, N.
          Ramsey, K.
          Abraham, A.
          Ryan, A.
          Rangasamy, S.
          Bonfitto, A.
          Naymik, M.
          Huentelman, M.
          Strom, S.
          Perry, D.
          Subramaniam, A.
          Grody, W. W.
          Szelinger, S.
          Narayanan, V.
        affil: Translational Genomics Research Institute (TGen), Phoenix Arizona,, USA
      sug:
        subj:
          Sequence Analysis
          Genome
          Genetic Screening Methods
          Hereditary Diseases Diagnosis
          Human
          Male
          Female
          Genetic Counseling
          Practice Guidelines
          Rare Diseases Diagnosis
          Reproductive Health
          Genomic Medicine
          Prepregnancy Care
          Pregnancy
          Funding Source
          Male
          Female
      ab: The goal of this study was to assess the feasibility of using exome (ES) and genome sequencing (GS) in guiding preconception genetic screening (PCGS) for couples who are planning to conceive by creating a workflow for identifying risk alleles for autosomal recessive (AR) and X‐linked (XL) disorders without the constraints of a predetermined, targeted gene panel. There were several limitations and challenges related to reporting and the technical aspects of ES and GS, which are listed in the discussion. We selected 150 couples from a cohort of families (trios) enrolled in a research protocol where the goal was to define the genetic etiology of disease in an affected child. Pre‐existing, de‐identified parental sequencing data were analyzed to define variants that would place the couple at risk of having a child affected by an AR or XL disorder. We identified 17 families who would be selected for counseling about risk alleles. We noted that only 3 of these at‐risk couples would be identified if we limited ourselves to the current ACMG‐recommended expanded carrier screening gene panel. ES and GS successfully identified couples who are at risk of having a child with a rare AR or XL disorder that would have been missed by the current recommended guidelines. Current limitations of this approach include ethical concerns, difficulties in reporting results including variant calling due to the rare nature of some of the variants, determining which disorders to report, as well as technical difficulties in detecting certain variants such as repeat expansions.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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