Population-dependent migration shift caused by sequence variation at the alpha fibrinogen (FGA) short tandem repeat...

The alpha fibrinogen (FGA) is a core short tandem repeat (STR) locus commonly used in forensic laboratories and is part of most of the commercial multiplex forensic STR kits. There are two distinct groups of FGA alleles based on their size: alleles 16-34.2 and 42.2-51.2. A thorough survey revealed that the long (>33) FGA alleles appear exclusively in populations of sub-Saharan Africans, Caribbean of African descent, non-African Arabs and peoples of non-African Arab descent. Our survey revealed that the long FGA alleles are rare and appear in only 0.01-1% of these populations, with the rarest allele being 47.2. The Israel Police DNA database includes about 470,000 DNA profiles, of which 193 bear an FGA allele longer than 33.2 and only 64 bearing the 47.2 allele. 30 samples with DNA profiles known to contain long FGA alleles were re-analyzed using three different STR multiplex kits. The regions of each long allele were sequenced in addition to STR analysis. The allele sequences revealed a striking difference in the pattern of repeats between the population groups of African and Arab descent. Eight of our samples contained the 47.2 allele, with a clear distinction between 47.2 sequences derived from African vs. Arab populations. In STR analysis, all 47.2 alleles displayed a shift from the allelic ladder bin center in all three kits. In all kits, the shift was significantly larger in the Arab population than in the African population. Hence, there is a population-dependent migration shift which may help differentiate profiles derived from different populations.