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| 1.
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Isshiki, Mariko ; Naka, Izumi ; Watanabe, Yusuke ; Nishida, Nao ; Kimura, Ryosuke ; Furusawa, Takuro ; Natsuhara, Kazumi ; Yamauchi, Taro ; Nakazawa, Minato ; Ishida, Takafumi ; Eddie, Ricky ; Ohtsuka, Ryutaro ; Ohashi, Jun
概要:
People in the Solomon Islands today are considered to have derived from Asian- and Papuan-related ancestors. Papuan-rela
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ted ancestors colonized Near Oceania about 47,000 years ago, and Asian-related ancestors were Austronesian (AN)-speaking population, called Lapita, who migrated from Southeast Asia about 3,500 years ago. These two ancestral populations admixed in Near Oceania before the expansion of Lapita people into Remote Oceania. To understand the impact of the admixture on the adaptation of AN-speaking Melanesians in Near Oceania, we performed the genome-wide single nucleotide polymorphism (SNP) analysis of 21 individuals from Munda, the main town of the New Georgia Islands in the western Solomon Islands. Population samples from Munda were genetically similar to other Solomon Island population samples. The analysis of genetic contribution from the two different ancestries to the Munda genome revealed significantly higher proportions of Asian- and Papuan-related ancestries in the region containing the annexin A1 (ANXA1) gene (Asian component > 82.6%) and in the human leukocyte antigen (HLA) class II region (Papuan component > 85.4%), respectively. These regions were suspected to have undergone natural selection since the time of admixture. Our results suggest that admixture had affected adaptation of AN-speaking Melanesians in the Solomon Islands.
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| 2.
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Furusawa, Takuro ; Naka, Izumi ; Yamauchi, Taro ; Natsuhara, Kazumi ; Eddie, Ricky ; Kimura, Ryosuke ; Nakazawa, Minato ; Ishida, Takafumi ; Ohtsuka, Ryutaro ; Ohashi, Jun
概要:
The people of the Solomon Islands represent an Austronesian (AN)-speaking population’s adaptation to a humid tropical en
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vironment and subsistence of tuberous crops. Genome-wide association studies (GWASs) of other populations (e.g. the Human Genome Diversity Project [HGDP]) have suggested the existence of genotypes adaptive to ecoregion, diet, and subsistence, and that those genotypes are also associated with metabolic and cardiovascular diseases. Recently, the incidence of non-communicable diseases has been increasing in the Solomon Islands. In the present study, we explored the association of genotypes adaptive to a tropical environment and tuberous crop diet with metabolic and cardiovascular conditions in rural and urban AN-speaking Melanesian and Micronesian populations of the Solomon Islands. A total of 561 participants were genotyped for single nucleotide polymorphisms (SNPs) potentially associated with a tropical environment (rs174570 and rs2237892) and a tuberous crop diet (rs162036, rs185819, and rs2722425). The results showed that the allele frequencies of the Solomon Islands populations adopted patterns similar to those in populations from other hot, tropical areas with a tuberous crop diet in previous studies. Furthermore, rs162036, rs185819, rs2237892, and rs2722425 were all strongly associated with one or more metabolic and cardiovascular conditions. The derived allele of rs2722425 (i.e. rs2722425-G) was significantly associated with an elevated LDL level (P = 0.000264) even after the significance level was adjusted for multiple testing (i.e., α = 0.0005). Our results suggest that the inhabitants of the Solomon Islands exhibit the effects of the tropical environment and tuberous crop diet on their allele frequencies, and that their susceptibility to metabolic and cardiovascular diseases is therefore considered to be associated with their environment and diet.
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| 3.
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Naka, Izumi ; Ohashi, Jun ; Kimura, Ryosuke ; Inaoka, Tsukasa ; Matsumura, Yasuhiro
概要:
Background:Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 loca
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ted in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations.\nMethods:To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga.\nResults:A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol.\nConclusions:In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index.
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| 4.
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Naka, Izumi ; Ohashi, Jun ; Kimura, Ryosuke ; Furusawa, Takuro ; Yamauchi, Taro ; Nakazawa, Minato ; Natsuhara, Kazumi ; Ataka, Yuji ; Nishida, Nao ; Ishida, Takafumi ; Inaoka, Tsukasa ; Matsumura, Yasuhiro ; Ohtsuka, Ryutaro
概要:
To study the origin of Polynesians and the gene flow from Polynesian ancestors to indigenous Melanesians, a 48-bp variab
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le number of tandem repeats (VNTR) in exon 3 of the dopamine D4 receptor (DRD4) gene was investigated for six Austronesian (AN)-speaking populations—two in Tonga (Nuku’alofa and Ha’apai), three in Solomon Islands (Munda, Paradise, and Rawaki, of whom Rawaki was a Micronesian migrant group), and one in Papua New Guinea (Balopa), and one Non-Austronesian (NAN)-speaking population in Papua New Guinea (Gidra). In these Oceanic populations, six VNTR alleles with 2 (2R) to 11 (7R) repeats were observed. The most frequent DRD4 VNTR allele was the 4R allele, although the allele frequencies of 2R and 7R varied markedly among them, characterized by high frequencies of 7R and lack of 2R in NAN-speaking Melanesians (Gidra), and high frequencies of 2R and low or null frequencies of 7R in AN-speaking Polynesians (Nuku’alofa and Ha’apai) and Micronesians (Rawaki). The allele frequency distribution of DRD4 VNTR in Polynesians was similar to that in Aboriginal Taiwanese (Ami and Atayal), supporting the hypothesis that Polynesian ancestors were derived from Southeast Asians (probably Taiwanese). A principal component analysis for Southeast Asian and Oceanic populations based on the DRD4 VNTR allele frequencies revealed that AN-speaking Melanesian populations were genetically placed between two AN-speaking Polynesian and one NAN-speaking Melanesian populations. These results provide evidence of gene flow from Polynesian ancestors to indigenous Melanesians while Polynesian ancestors passed through Melanesia.
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| 5.
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Myles, Sean ; Lea, Rod A. ; Ohashi, Jun ; Chambers, Geoff K. ; Weiss, Joerg G. ; Hardouin, Emilie ; Engelken, Johannes ; Macartney-Coxson, Donia P. ; Eccles, David A. ; Naka, Izumi ; Kimura, Ryosuke ; Inaoka, Tsukasa ; Matsumura, Yasuhiro ; Stoneking, Mark
概要:
Background:The thrifty gene hypothesis posits that, in populations that experienced periods of feast and famine, natural
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selection favoured individuals carrying thrifty alleles that promote the storage of fat and energy. Polynesians likely experienced long periods of cold stress and starvation during their settlement of the Pacific and today have high rates of obesity and type 2 diabetes (T2DM), possibly due to past positive selection for thrifty alleles. Alternatively, T2DM risk alleles may simply have drifted to high frequency in Polynesians. To identify thrifty alleles in Polynesians, we previously examined evidence of positive selection on T2DM-associated SNPs and identified a T2DM risk allele at unusually high frequency in Polynesians. We suggested that the risk allele of the Gly482Ser variant in the PPARGC1A gene was driven to high frequency in Polynesians by positive selection and therefore possibly represented a thrifty allele in the Pacific.\nMethods:Here we examine whether PPARGC1A is a thrifty gene in Pacific populations by testing for an association between Gly482Ser genotypes and BMI in two Pacific populations (Maori and Tongans) and by evaluating the frequency of the risk allele of the Gly482Ser variant in a sample of worldwide populations.\nResults:We find that the Gly482Ser variant is associated with BMI in Tongans but not in Maori. In a sample of 58 populations worldwide, we also show that the 482Ser risk allele reaches its highest frequency in the Pacific.\nConclusion:The association between Gly482Ser genotypes and BMI in Tongans together with the worldwide frequency distribution of the Gly482Ser risk allele suggests that PPARGC1A remains a candidate thrifty gene in Pacific populations.
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| 6.
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Ohashi, Jun ; Naka, Izumi ; Kimura, Ryosuke ; Tokunaga, Katsushi ; Nakazawa, Minato ; Ataka, Yuji ; Ohtsuka, Ryutaro ; Inaoka, Tsukasa ; Matsumura, Yasuhiro
概要:
HLA-DRB1 polymorphism was investigated by molecular DNA-based typing in 37 Tongans living on Ha’ano island of the Ha’apa
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i group. The predominant HLA-DRB1 alleles were DRB1*0901 (20.3%) and DRB1*0403 (18.9%). A principal component analysis of the DRB1 allele frequencies discriminated between the Polynesians and other Oceanian populations, including Melanesians, Micronesians, and Australian Aborigines. Both present and previous studies have shown that the allele frequency of DRB1*0901 is markedly high in Polynesians and Asians, while this allele is seldom found in Non-Austronesian (NAN)-speaking Melanesians, Micronesians, and Australian Aborigines. Furthermore, we analyzed the frequencies of allele coding for Arg at position 196 (196R: nucleotide [nt] 587G) of tumor necrosis factor receptor 2 (TNFR2, TNF-R75) in three Oceanian populations: Tongans, Austronesian (AN)-speaking Balopa islanders living in Manus province of Papua New Guinea, and NAN-speaking Gidra living in the southwestern lowlands of Papua New Guinea. The frequencies of the TNFR2-196R allele, observed at a relatively high frequency in East and Southeast Asian populations, were 24.0%, 7.3%, and 1.0% in the Tongans, Balopa islanders, and Gidra, respectively. Considering that the allele frequencies of DRB1*0901 and TNFR2 196R are relatively high in Asians, Polynesians, and AN-speaking Melanesians (Balopa islanders), but very low in NAN-speaking Melanesians (Gidra), we conclude that at least part of the AN-speaking Polynesian ancestors were derived from Asian populations, and that extensive gene flow from the Polynesian ancestors to the indigenous Melanesians occurred around their initial migration to Melanesia. This is consistent with the results from analyses of mitochondrial DNA and ABO blood group gene polymorphisms in the same study populations.
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