Paths and timings of the peopling of Polynesia inferred from genomic networks.

Polynesia was settled in a series of extraordinary voyages across an ocean spanning one third of the Earth1, but the sequences of islands settled remain unknown and their timings disputed. Currently, several centuries separate the dates suggested by different archaeological surveys2-4. Here, using genome-wide data from merely 430 modern individuals from 21 key Pacific island populations and novel ancestry-specific computational analyses, we unravel the detailed genetic history of this vast, dispersed island network. Our reconstruction of the branching Polynesian migration sequence reveals a serial founder expansion, characterized by directional loss of variants, that originated in Samoa and spread first through the Cook Islands (Rarotonga), then to the Society (Totaiete ma) Islands (11th century), the western Austral (Tuha'a Pae) Islands and Tuamotu Archipelago (12th century), and finally to the widely separated, but genetically connected, megalithic statue-building cultures of the Marquesas (Te Henua 'Enana) Islands in the north, Raivavae in the south, and Easter Island (Rapa Nui), the easternmost of the Polynesian islands, settled in approximately AD 1200 via Mangareva.

Genetic characterization of N-acetyltransferase 2 variants in acquired multidrug-resistant tuberculosis in Indonesia.

Background: Owing to the high resistance rate of tuberculosis (TB) to isoniazid, which is metabolized by N-acetyltransferase 2 (NAT2), we investigated the associations between NAT2 variants and multidrug-resistant (MDR)-TB. Materials & methods: The acetylator status based on NAT2 haplotypes of 128 patients with MDR-TB in Indonesia were compared with our published data from patients with anti-TB drug-induced liver injury (AT-DILI), TB and the general population. Results:NAT2*4 was more frequent in the MDR-TB group than in the AT-DILI group, TB controls and general controls. NAT2*4/*4 was significantly more frequent in patients with MDR-TB than in those with AT-DILI. NAT2*5B/7B, *6A/6A and *7B/*7B were detected at lower frequencies in patients with AT-DILI. Rapid acetylators were significantly more frequent in patients with MDR-TB than in those with AT-DILI. Conclusion: These results provide an initial data for optimizing TB treatment in the Indonesian population, and suggest that NAT2 genotyping may help to select appropriate treatment by predicting TB-treatment effect.

Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: A study on ß-thalassemia and hemoglobin E/ß-thalassemia patients in Indonesia.

OBJECTIVE/BACKGROUND: Thalassemia is a monogenic hematologic disease that has the highest prevalence globally. In addition, there is complexity of the genetic background associated with a variety of phenotypes presented among patients. Genetic heterogeneity related to fetal hemoglobin (HbF) production has been reported as an influencing phenotypic factor of ß-thalassemia (ß-thal). Therefore, this study aimed to find the effect of these genetic modifiers, especially in the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB), among ß-thal and HbE/ß-thal patients in Indonesia, according to laboratory and clinical outcomes, including HbF levels and clinical scores. This study was also designed to compare these modifying effects among ß-thal and HbE/ß-thal patients in Indonesia. METHODS: A total of 189 patients with genotyping of ß-thal and HbE/ß-thal were included in this study. The erythrocytes index and Hb electrophoresis measurements were calculated using appropriate methods. The severity of ß-thal and HbE/ß-thal was classified based on the Mahidol score. Polymorphism of the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS) methods. RESULTS: The distributions of minor allele in the XmnI locus, rs11886868, rs766432, and rs9399137 were 14%, 22%, 19% and 18% respectively. The variation allele in the XmnI locus, rs11886868, and rs766432 showed a significant value for modifying HbF and clinical score in HbE/ß-thal patients, but rs9399137 did not demonstrate such features. In ß-thal patients, however, no correlation was found for any single-nucleotide polymorphisms and clinical appearance. CONCLUSION: The XmnI locus, rs11886868, and rs766432 have a modifying effect on HbF and clinical score in HbE/ß-thal patients in Indonesia, but not in ß-thal patients.

Molecular Scanning of ß-Thalassemia in the Southern Region of Central Java, Indonesia; a Step Towards a Local Prevention Program.

Thalassemia is the most prevalent genetic blood disorder worldwide, and particularly prevalent in Indonesia. The purpose of this study was to determine the spectrum of ß-thalassemia (ß-thal) mutations found in the southern region of Central Java, Indonesia. The subjects of the study included 209 ß-thal Javanese patients from Banyumas Residency, a southwest region of Central Java Province. DNA analysis was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS), and the direct sequencing method. The results showed that 14 alleles were found in the following order: IVS-I-5 (G > C) (HBB: c.92 + 5G > C) 43.5%, codon 26 (Hb E; HBB: c.79G > A) 28.2%, IVS-I-1 (G > A) (HBB: c.92 + 1G > A) 5.0%, codon 15 (TGG > TAG) (HBB: c.47G > A) 3.8%, IVS-I-1 (G > T) (HBB: c.92 + 1G > T) 3.1%, codon 35 (-C) (HBB: c.110delC) 2.4%. The rest, including codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), codons 8/9 (+G) (HBB: c.27_28insG), codon 19 (AAC > AGC) (HBB: c.59A > G), codon 17 (AAG > TAG) (HBB: c.52A > T), IVS-I-2 (T > C) (HBB: c.92 + 2T > C), codons 123/124/125 (-ACCCCACC) (HBB: c.370_378delACCCCACCA), codon 40 (-G) (HBB: c.123delG) and Cap +1 (A > C) (HBB: c.-50A > C), accounted for up to 1.0% each. The most prevalent alleles would be recommended to be used as part of ß-thal screening for the Javanese, one of the major ethnic groups in the country.

Status of Superoxide Dismutase in Transfusion Dependent Thalassaemia.

BACKGROUND: Thalassemia is a collection of genetic impairments in beta and alpha genes causing various states of anemia. Severe types of the disease need lifelong transfusions, leading to oxidant-antioxidant disturbance due to massive iron deposits. AIMS: The aim of this study was to assess the antioxidant enzyme Superoxide Dismutase (SOD) and ferritin levels of thalassemia major patients in a peripheral health facility. MATERIALS AND METHODS: Two hundred and nine probands were recruited and performed laboratory experiments for SOD and Ferritin levels. Chelation administration and clinical score were taken from interviewing the family and from medical report data. RESULTS: The study showed that SOD intensity was lower (162.41 u/ml) compared to the normal cutoff point (P = 0.001), while the mean of Ferritin levels was ten times over the normal value (4226,67 ng/dl). Observations also reported that chelation medicine was not administrated properly. CONCLUSIONS: The data indicates that thalassemic patients have oxidant-antioxidant uproar due to oxidative stress. Monitored chelating administration, selective antioxidant, and a well-balanced diet may prevent oxidative injury.

The C677T mutation in the methylenetetrahydrofolate reductase gene among the Indonesian Javanese population.

The presence of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene has been regarded as a genetic risk factor for coronary artery diseases and neural tube defects. Although the prevalence of this mutation has been reported from various ethnic populations, few data concerning Indonesian populations are available. We have investigated the frequency of the mutation in 68 Indonesian Javanese (residents of Java Island) and compared it with the data from 244 Japanese (residents of Honshu Island). The frequencies of the three genotypes in Javanese were C/C 0.84, C/T 0.16 and T/T 0.00, whereas those in Japanese were C/C 0.39, C/T 0.48 and T/T 0.13. The rarity of the T/T genotype in the Indonesian Javanese population may be due to malnutrition in pregnant women, because insufficient intake of folate is considered to be a survival disadvantage for fetuses with the T/T genotype. In conclusion, homozygosity for the C677T mutation in the MTHFR gene does not constitute a genetic risk factor for coronary artery diseases and neural tube defects in the Indonesian Javanese population.