| Glucose-6-phosphate dehydrogenase(G6PD) deficiency and thalassemia are two of the most common genetic blood diseases, posing a threat to human health. About 400 million people are suffered from G6 PD deficiency, and 276 million people are ?-thalassaemia carriers; 80~ 90 million are ?-thalassaemia carriers worldwide. Individuals originating from tropical and subtropical regions, such as Africa, the Middle East, the Mediterranean region and Southeast Asia, are highly at risk, where malaria was once common. The geographical distribution of G6 PD deficiency and thalassemia are closely related to the prevalence of malaria because of a selective advantage against malaria infection, which probably explains its high frequency in the tropical and subtropical regions. In China, G6 PD deficiency is always accompanied with thalassemia in southern subtropical areas, such as Guangdong, Guangxi, Yunnan and Hainan provinces, but is found less in northern regions. Thalassemia was once reported in Shanxi, Gansu, Xinjiang provinces wherethe region has been regarded as a part of the ancient Silk Road. Xinjiang, a part of Central Asia, which is adjacent to Mongolia, Russia, Kazakhstan, Kyrgyzstan, Tajikistan, Afghanistan, Pakistan and India, has the longest border in China. Among the 56 recognized ethnic groups in China, 13 are found in Xinjiang, where the largest ethnic minority among the resident is Uygur. The Uygur and Kazak are the Eurasianpopulation with Eastern and Western Eurasian anthropometric and genetic traits. Evidence from mitochondrial DNA(mt DNA) and Y chromosome also supported that Uygur and Kazak are hybrids of both Caucasian and Mongoloid. Heretofore, the prevalence of G6 PD deficiency in Xinjiang has not been clearly defined by any researchers. Here, we aimed to answer the questions: what the prevalence of G6 PD deficiency and thalassemia are in Uygur and Kazak ethic groups in Xinjiang and whether or not thalassemia is accompanied with G6 PD deficiency in these populations. Malaria is the strongest known force for evolutionary selection in the recent history of the human genome, and is the evolutionary driving force behind, thalassemia, G6 PD deficiency, sickle-cell disease, and other erythrocyte defects that together comprise the most common Mendelian diseases of humankind. Under pressure from the advantage to select, G6 PD and ??? genes formed several SNPs of highly linkage disequilibrium(LD) section. According to our research, we research further significance of haploid domain selection, genetic polymorphisms among different groups, the relationship between genetic and disease, and enrich a complete human genome database of the minority's origin,evolution and migration.We used the NBT(nitroblue tetrazolium) paper strip method for G6 PD activity screening and none showed any G6 PD enzyme activity deficiency. Genomic DNA was extracted by blood samples in EDTA-containing vacutainers, that were collected from 149 patients attending the First Financial Aid Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China, including 138 Uygur subjects(44 males and 94 females) and 11 Kazak(six males and five females). All PCR amplification products were tested by DHPLC and direct sequencing to work out the relationship between genotype and phenotype. Our analysis of genomic DNA samples from non-G6 PD deficiency individuals revealed that the percentages of subjects who had the c.1311C>T mutations were 29.0%(40/138) Uygurs, 36.0%(4/11) Kazaks; IVSXI+93T>C mutations were 37.0%(51/138) Uygurs and 36.0%(4/11) Kazaks. Meanwhile, SNP rs398123547, rs56262786 and rs1050757 were found in Uygurs. We also detected two novel SNPs on intron 10 and intron 11 in Uygurs, c.1287+48G>A and c.1364+48C>T that have not been reported in Han people before.Of the 149 blood samples, 36 cases(33 Uygur and three Kazak subjects) showed an MCH value of <27.0 pg and an MCV value of <82.0 f L, and samples from seven Uygur subjects, who had a normal MCV and a reduced MCH value, were analyzed by the gap-PCR and PCR sequencing to detect disease-caused mutations of the ???-globin genes. Three common deletional ?-thal(--SEA,??/-?3.7,??/-?4.2) and other point mutations of the ?-globin gene were not observed in the Uygurs and Kazaks in the present study. In Uygur, we found a heterozygote for the HBB: c.135 del C [codon 44(?C)] mutation(0.72%, 1/138), with reduced MCV and MCH values. Another Uygur subject was a heterozygote for the HBB: c.68A>G(Hb G-Taipei) with reduced MCV levels(0.72%, 1/138). Seven kinds of ?-globin gene SNPs, rs713040, rs10768683, rs7480526, rs1609812, rs12788013, rs140033163, rs7946748 were observed in Uygur and Kazak subjects, and rs713040, rs10768683, rs7480526, rs1609812 were also found in Guangdong Hakka people in previous research. G6 PD gene of Uygur group has a number of SNPs to formed a haplotype block, in which, c.1311C>T and IVSXI+93T>C, rs1050757 G exist linkage disequilibrium. The haplotype of ?-globin revealed a high linkage disequilibrium in rs713040, rs10768683, rs7480526. Kazak samples are not enough to build the haplotype since we could not show the linkage.These two diseases exist simultaneously in populations in southern China, probably because both of them could protect individuals from malaria. The G6 PD deficiency patients were not found in Xinjiang, which might result from its geographical position and low incidence of malaria because of the temperate continental climate. Further studies are needed to clarify why there is still a low incidence of abnormal hemoglobinopathy in Xinjiang. Nevertheless, according to our research, it might explained by the existence of ?-globin gene drifting between the population in Middle East, Mediterranean region and Uygur people. The c.1311C>T polymorphism at G6 PD exon 11 is prevalent among various populations around the globe. HBB: c.135 del C is frequently reported in Kurdish Jews but is quite rare in populations around the Mediterranean Sea, the Middle East and Xinjiang. However, HBB: c.68A>G is widely spread in China. Given the high frequency of variants of G6 PD, ?-globin genes, we considered the Uygurs and Kazaks to be a hybrid race of both Caucasian and Mongoloid from the perspective of genetic blood diseases. Genetic polymorphism studies help to identify the presence of a gene in different regions as well as in different population groups. The G6 PD and ?-globin genes contain a considerable number of polymorphic markers that would help us to research the origin and evolution of Uygur and Kazak. In summary, our results expand the previously reported genetic information related to G6 PD deficiency and thalassemia in China. We firstly reported the phenotype and genotype in G6 PD deficiency among Uygur and Kazak populations, built the two haplotype block both on G6 PD gene and ?-globin gene. |
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