Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Estimating the age of p.(Phe508del) with family studies of geographically distinct European populations and the early spread of cystic fibrosis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Haploinsufficiency of ARHGAP42 is associated with hypertension

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Correction: Educational delay and attainment in persons with neurofibromatosis 1 in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. The Global State of the Genetic Counseling Profession

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  4. A Faroese founder variant in TBCD causes early onset, progressive encephalopathy with a homogenous clinical course

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Genetic analysis of Charcot-Marie-Tooth disease in Denmark and the implementation of a next generation sequencing platform

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Mosaic MECP2 variants in males with classical Rett syndrome features, including stereotypical hand movements

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Peripheral neuropathy in hereditary spastic paraplegia caused by REEP1 variants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Osteogenesis imperfecta and the teeth, eyes, and ears-a study of non-skeletal phenotypes in adults

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Philip Farrell
  • Claude Férec
  • Milan Macek
  • Thomas Frischer
  • Sabine Renner
  • Katharina Riss
  • David Barton
  • Teresa Repetto
  • Maria Tzetis
  • Karine Giteau
  • Morten Duno
  • Melissa Rogers
  • Hara Levy
  • Mourad Sahbatou
  • Yann Fichou
  • Cédric Le Maréchal
  • Emmanuelle Génin
Vis graf over relationer

The high incidence of cystic fibrosis (CF) is due to the frequency of the c.1521_1523delCTT variant in the cystic fibrosis transmembrane conductance regulator (CFTR), but its age and origin are uncertain. This gap limits attempts to shed light on the presumed heterozygote selective advantage that accounts for the variant's high prevalence among Caucasian Europeans and Europe-derived populations. In addition, explaining the nature of heterozygosity to screened individuals with one c.1521_1523delCTT variant is challenging when families raise questions about these issues. To address this gap, we obtained DNA samples from 190 patients bearing c.1521_1523delCTT and their parents residing in geographically distinct European populations plus a Germany-derived population in the USA. We identified microsatellites spanning CFTR and reconstructed haplotypes at 10 loci to estimate the time/age of the most recent common ancestor (tMRCA) with the Estiage program. We found that the age estimates differ between northwestern populations, where the mean tMRCA values vary between 4600 and 4725 years, and the southeastern populations where c.1521_1523delCTT seems to have been introduced only about 1000 years ago. The tMRCA values of Central Europeans were intermediate. Thus, our data resolve a controversy by establishing an early Bronze Age origin of the c.1521_1523delCTT allele and demonstrating its likely spread from northwest to southeast during ancient migrations. Moreover, taking the archeological record into account, our results introduce a novel concept by suggesting that Bell Beaker folk were the probable migrating population responsible for the early dissemination of c.1521_1523delCTT in prehistoric Europe.

OriginalsprogEngelsk
TidsskriftEuropean journal of human genetics : EJHG
Vol/bind26
Udgave nummer12
Sider (fra-til)1832-1839
Antal sider8
ISSN1018-4813
DOI
StatusUdgivet - dec. 2018

ID: 56214236