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Nine independent F9 mutations in the Mexican hemophilia B population: Nonrandom recurrences of point mutation events in the human germline

✍ Scribed by Ana Rebeca Jaloma-Cruz; William A. Scaringe; Joni B. Drost; Stacy Roberts; Xuemin Li; Patricio Barros-Núñez; Luis E. Figuera; Fernando Rivas; José María Cantú; Steve S. Sommer


Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
26 KB
Volume
15
Category
Article
ISSN
1059-7794

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✦ Synopsis


The factor IX gene (F9) is a valuable model for studying germ-line mutations. Nine mutations were detected in nine Mexican patients with hemophilia B by direct sequencing using genomic amplification with transcript sequencing (GAWTS): six single base changes, one micro-deletion, and two large deletions. Germline origins of mutations were found in three of six families with sporadic cases. Curiously, the four independent single base substitutions which were not at CpG dinucleotides occurred at only two different nucleotide positions (17,678 and 17,747) one transition and one transversion at each. The two remaining substitutions were identical changes at a CpG dinucleotide, but were determined to be independent by germline origin analysis. A statistical analysis suggests that the independent recurrence of mutations at these locations may reflect an unusual aspect of F9 mutagenesis in the Mexican population. These data raise the possibility of population-specific differences in human germline mutations.