RESUMO
BACKGROUND: The human FUT2 gene, which encodes a secretor type α(1,2)fucosyltransferase, is reported to have several population-specific single-nucleotide polymorphisms (SNPs) and copy number variations. However, little is known about genetic variation of FUT2 in Native Americans. STUDY DESIGN AND METHODS: To detect SNPs and copy number variations of the FUT2 gene in Peruvians, direct sequencing and digital polymerase chain reaction were performed. Haplotypes of observed SNPs were estimated by PHASE software or cloning into plasmids. The functional significance of nonsynonymous SNPs was examined by transient transfection assay. RESULTS: We identified three novel nonfunctional alleles (se178,357 , se841 , and sedel4 ) due to two nonsynonymous SNPs (178C > T and 841G > A) and a novel long terminal repeat-mediated recombination with a 4.3-kb deletion in 70 Peruvians. The frequency of nonfunctional alleles was relative low (20.7%). Because se841 has a relatively high frequency (5.7%), it might be a suitable genetic marker for Peruvians. CONCLUSION: We identified three novel nonfunctional alleles in 70 Peruvians. To our knowledge, this is the first time a long terminal repeat-mediated gene recombination event at the FUT2 locus has been detected.
Assuntos
Sequência de Bases , Variações do Número de Cópias de DNA , Fucosiltransferases/genética , Indígenas Sul-Americanos/genética , Polimorfismo de Nucleotídeo Único , Deleção de Sequência , Sequências Repetidas Terminais , Alelos , Feminino , Frequência do Gene , Humanos , Masculino , Peru , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
Delta-aminolevulinic acid dehydratase (ALAD) is a cytosolic enzyme in the heme biosynthetic pathway. The ALAD is controlled by two codominant alleles (ALAD1 and ALAD2), which result in a Asn-Lys substitution at amino acid position 59 of the mature enzyme based on a single nucleotide polymorphism (SNP) (G177C) leading three phenotypes (ALAD1-1, ALAD1-2, and ALAD2-2). Previous studies have shown that this polymorphism is related to lead toxicity. There is little evidence showing interethnic differences in the distribution of this polymorphism. We examined the distribution of genetic variants of the ALAD G177C polymorphism in four Asians, three Africans, and three Mexicans. Genomic DNA was extracted from blood or bloodstain, and the genotypes for the ALAD polymorphism were determined by PCR followed by RFLP digestion and gel electrophoresis. We found a notable interethnic disparity in the distribution of ALAD G177C genotypes and alleles. The frequencies of ALAD2 in Asian populations were comparable to those in Caucasians, while Africans had no mutation allele. These findings may help us understand the interethnic disparities in susceptibility to lead toxicity.