Factor IX gene haplotypes in Brazilian Blacks and characterization of unusual Ddel alleles

Abstract

Analysis of factor IX gene polymorphisms is considered the best approach for prenatal diagnosis and carrier detection of haemophilia B when the identification of the gene mutation is not possible. Studies involving factor IX gene polymorphisms in Black populations are scarce and essentially restricted to the North-American Black population whose composition is substantially different from that of the Brazilian and presumably other Black populations of South America. In this paper we report the analysis of eight factor IX gene polymorphisms in Brazilian Blacks: 5' BamHI, DdeI, intron 2 BamHI, XmnI, TaqI, TaqI, MspI, MnlI and HhaI. Characterization of the VNTR-like DdeI polymorphism revealed six different alleles: B, AB, A2B, A2B2, A3B and A5B, the last being described here for the first time. The 5' BamHI, DdeI, MspI and HhaI polymorphisms showed the highest heterozygosities (0.40-0.50) and are in linkage equilibrium with one another. 19 complete haplotypes could be identified in this population. Based on the results we propose a systematic strategy for carrier detection and prenatal diagnosis of haemophilia B in this population. The combined analysis of four polymorphisms (5' BamHI, HhaI, MspI and DdeI) provided an informative genetic marker in 85% of the females. The use of all eight polymorphisms allows information in 95% of females. Additionally, differences in gene frequencies and haplotype distribution suggest dissimilarities in factor IX gene polymorphisms between the Brazilian and the North-American Black populations.

The molecular analysis of haemophilia B: a guideline from the UK haemophilia centre doctors’ organization haemophilia genetics laboratory network

“…The entire ∼35 kb of the FIX gene has been sequenced, but no short tandem repeat polymorphisms have been found. However, the Dde I polymorphism in intron 1 is a complex repeat [25] having two common and several rare alleles and a Caucasian heterozygosity rate of 35%, making it a useful component of a panel of markers for linkage analysis.…”

Interpopulational and Intrapopulational Genetic Diversity of Amerindians as Revealed by Six Variable Number of Tandem Repeats

“…We were careful to try to exclude mulattos from the Black sample, although figures of estimated admixture with Caucasians are not available. A low admix ture with Caucasians is indicated by the close agreement of allele frequencies distribution of D1S80 and ApoB 3' VNTR with other Black populations, as well as by the results of analy sis of the factor VIII and factor IX genes poly morphisms in this population [36,41], Brazil ian Blacks are descendants of African slaves and are genetically very different from North American and Caribbean Blacks, as demon strated by the predominance of genes of Ban tu origin as compared with genes of Benin ori gin and very rare genes originated from the Senegambia [42], The Japanese sample com prised Japanese immigrants or their first-or second-generation descendants.…”

Assessment of the carrier status by pedigree analysis in some families from India

“…It was also mentioned that although the study of restriction fragment length polymorphisms is the preferred method in familial haemophilia, it is less useful in isolated cases [14]. DNA polymorphism studies also revealed that some single polymorphic sites can assess the carrier status up to approximately 30% whereas three or more probes can give the results up to 90% [15][16][17][18][19]. In another study, racial variations were also seen, i.e.…”