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@ARTICLE{Ahmad:277324,
      author       = {O. Ahmad$^*$ and C. Sutter and S. Hirsch$^*$ and S.
                      Pfister$^*$ and C. P. Schaaf},
      title        = {{BRCA}1/2 potential founder variants in the {J}ordanian
                      population: an opportunity for a customized screening
                      panel.},
      journal      = {Hereditary cancer in clinical practice},
      volume       = {21},
      number       = {1},
      issn         = {1731-2302},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2023-01342},
      pages        = {11},
      year         = {2023},
      note         = {#EA:B062#},
      abstract     = {A founder variant is a genetic alteration, that is
                      inherited from a common ancestor together with a surrounding
                      chromosomal segment, and is observed at a high frequency in
                      a defined population. This founder effect occurs as a
                      consequence of long-standing inbreeding of isolated
                      populations. For high-risk cancer predisposition genes, such
                      as BRCA1/2, the identification of founder variants in a
                      certain population could help designing customized
                      cost-effective cancer screening panels. This advantage has
                      been best utilized in designing a customized breast cancer
                      BRCA screening panel for the Ashkenazi Jews (AJ) population,
                      composed of the three BRCA founder variants which account
                      for approximately $90\%$ of identified BRCA alterations.
                      Indeed, the high prevalence of pathogenic BRCA1/2 variants
                      among AJ (~ $2\%)$ has additionally contributed to make
                      population-based screening cost-effective in comparison to
                      family-history-based screening. In Jordan there are multiple
                      demographic characteristics supporting the proposal of a
                      founder effect. A high consanguinity rate of ~ $57\%$ in the
                      nineties of the last century and ~ $30\%$ more recently is a
                      prominent factor, in addition to inbreeding which is often
                      practiced by different sub-populations of the country.This
                      review explains the concept of founder effect, then applies
                      it to analyze published Jordanian BRCA variants, and
                      concludes that nine pathogenic (P) and likely pathogenic
                      (LP) BRCA2 variants together with one pathogenic BRCA1
                      variant are potential founder variants. Together they make
                      up $43\%$ and $55\%$ of all identified BRCA1/2 alterations
                      in the two largest studied cohorts of young patients and
                      high-risk patients respectively. These variants were
                      identified based on being recurrent and either specific to
                      ethnic groups or being novel. In addition, the report
                      highlights the required testing methodologies to validate
                      these findings, and proposes a health economic evaluation
                      model to test cost-effectiveness of a population-based
                      customized BRCA screening panel for the Jordanian
                      population. The aim of this report is to highlight the
                      potential utilization of founder variants in establishing
                      customized cancer predisposition services, in order to
                      encourage more population-based genomic studies in Jordan
                      and similar populations.},
      subtyp        = {Review Article},
      keywords     = {BRCA1 (Other) / BRCA2 (Other) / Breast cancer (Other) /
                      Customized screening panel (Other) / Founder variants
                      (Other) / Jordan (Other) / Population-based screening
                      (Other)},
      cin          = {B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37400873},
      doi          = {10.1186/s13053-023-00256-2},
      url          = {https://inrepo02.dkfz.de/record/277324},
}