Germline mutations in Peruvian patients with hemophilia B: Pattern of mutation in AmerIndians is similar to the putative endogenous germline pattern

John A. Heit, Erik C. Thorland, Rhett P. Ketterling, Tammy J. Lind, Todd M. Daniels, Renee Eyzaguirre Zapata, Saul Mendoza Ordonez, Carol K. Kasper, Steve S. Sommer

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Exogenous (e.g., environmental) mutagens produce characteristic patterns of mutation. In contrast, endogenous mutation processes likely are associated with an invariant pattern of mutation. Analysis of factor IX gene mutations among large samples of hemophilia B patients from multiple, widely divergent geographic and ethnic populations reveals a remarkably constant mutational pattern, suggesting that the primary germline mutational process results from endogenous processes rather than environmental mutagens. To test this hypothesis further, we have initiated a study of hemophilia B patients from Peru because relatively large populations of AmerIndians can be found with low admixtures of other races. To determine if the factor IX (FIX) germline mutational pattern in AmerIndians differs from the common and putative endogenous pattern, FIX gene mutations were characterized in an initial sample of 10 AmerIndian Peruvian patients with hemophilia B. A minimum of 2.2 kb of the FIX gene was examined by PCR and direct sequencing of all eight exons, the splice junctions, and the promoter region. The pattern of germline mutation in AmerIndians was similar to the pattern of FLX germline mutations from larger U.S. Caucasian or Mexican Hispanic samples (P=0.55 and 0.63, respectively). The similar pattern in this initial sample of the Peru AmerIndian population provides additional support for the inference that the FIX germline mutational pattern results from predominantly endogenous processes rather than exogenous mutagens.

Original languageEnglish (US)
Pages (from-to)372-376
Number of pages5
JournalHuman mutation
Volume11
Issue number5
DOIs
StatePublished - Jan 1 1998

Keywords

  • Factor IX
  • Mutagens
  • Mutations
  • Race

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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