Mitochondrial Genome Variation and Metabolic Traits in a Maori Community

<p>The mitochondrion is the energy producing factory of cells and it has long been thought that disruption to mitochondrial systems is linked to energy metabolism dysfunction. Sequence variants in the mitochondrial genome are plausible candidate risk factors for numerous human diseases, and research has identified specific mitochondrial DNA (mtDNA) variants associated with metabolic disorders such as obesity and type-2 diabetes. As part of the Rakaipaaka Health and Ancestry Study (RHAS) it has been observed that the Maori community of Nuhaka (Ngati Rakaipaaka) have a high incidence of certain metabolic diseases, namely obesity and diabetes. The reason for this is not well understood, but is likely to be a combination of both current lifestyle (e.g. dietary) and ancestral genetic factors. This study set out to sequence the entire mitochondrial genome in a sample of RHAS Maori participants. The aim was to discover genetic variation that might be specific to this Maori community and test whether such variants are associated with diabetes and other metabolic traits. This study used a novel RFLP assay to screen the mtDNA control region for Polynesian mtDNA ancestry. This established an initial group (n=30) with high levels of Maori mtDNA. Hypervariable (HVRI) sequencing was then used to generate a large dataset of sequences (n=94). This dataset was representative of individuals showing high Maori ancestry and aided the selection of 20 mtDNA's for Mitochip analysis. Combining the RHAS Maori HVRI sequences with those from previous studies indicated elevated variation in Maori mtDNA. Haplotype analysis identified 17 unique Maori haplotypes, 10 more than previously recorded. Mitochip resequencing has provided the first complete Maori mtDNA sequences to date. When compared to other mtDNA sequences it was identified that RHAS Maori share similar haplotype markers with Polynesians. Seven novel undocumented variants were found, as well as four variants that had previously been associated with various metabolic disorders. Mitochip analysis of mtDNA sequences revealed three variants which created a RHAS Maori specific signature; C1185T, G4769A, and T16126C. These variants also defined 3 unique mtDNA haplotypes within RHAS Maori, which are the first Maori specific haplotypes reported. Variant genotyping and correlation with metabolic traits identified significant associations within the wider RHAS Maori community. It was identified that RHAS Maori with T16189C showed elevation in both vitamin B12 levels and mean diastolic blood pressure. Individuals with the G4769A variant were shown to have significant increases in specific metabolic risk factors for cardiovascular disease. Conversely individuals with the more common A4769G variant were 2 times less likely to be diagnosed with diabetes. The findings from this study have identified a series of potential markers of metabolic disease within the RHAS Maori community. The goal now is to understand how these markers interact with environmental variables to increase the risk of metabolic syndrome. Such an outcome may open the way to designing personalised intervention strategies (e.g. dietary) to increase the health and well-being of at risk individuals.</p>

Mitochondrial Genome Variation and Metabolic Traits in a Maori Community

<p>The mitochondrion is the energy producing factory of cells and it has long been thought that disruption to mitochondrial systems is linked to energy metabolism dysfunction. Sequence variants in the mitochondrial genome are plausible candidate risk factors for numerous human diseases, and research has identified specific mitochondrial DNA (mtDNA) variants associated with metabolic disorders such as obesity and type-2 diabetes. As part of the Rakaipaaka Health and Ancestry Study (RHAS) it has been observed that the Maori community of Nuhaka (Ngati Rakaipaaka) have a high incidence of certain metabolic diseases, namely obesity and diabetes. The reason for this is not well understood, but is likely to be a combination of both current lifestyle (e.g. dietary) and ancestral genetic factors. This study set out to sequence the entire mitochondrial genome in a sample of RHAS Maori participants. The aim was to discover genetic variation that might be specific to this Maori community and test whether such variants are associated with diabetes and other metabolic traits. This study used a novel RFLP assay to screen the mtDNA control region for Polynesian mtDNA ancestry. This established an initial group (n=30) with high levels of Maori mtDNA. Hypervariable (HVRI) sequencing was then used to generate a large dataset of sequences (n=94). This dataset was representative of individuals showing high Maori ancestry and aided the selection of 20 mtDNA's for Mitochip analysis. Combining the RHAS Maori HVRI sequences with those from previous studies indicated elevated variation in Maori mtDNA. Haplotype analysis identified 17 unique Maori haplotypes, 10 more than previously recorded. Mitochip resequencing has provided the first complete Maori mtDNA sequences to date. When compared to other mtDNA sequences it was identified that RHAS Maori share similar haplotype markers with Polynesians. Seven novel undocumented variants were found, as well as four variants that had previously been associated with various metabolic disorders. Mitochip analysis of mtDNA sequences revealed three variants which created a RHAS Maori specific signature; C1185T, G4769A, and T16126C. These variants also defined 3 unique mtDNA haplotypes within RHAS Maori, which are the first Maori specific haplotypes reported. Variant genotyping and correlation with metabolic traits identified significant associations within the wider RHAS Maori community. It was identified that RHAS Maori with T16189C showed elevation in both vitamin B12 levels and mean diastolic blood pressure. Individuals with the G4769A variant were shown to have significant increases in specific metabolic risk factors for cardiovascular disease. Conversely individuals with the more common A4769G variant were 2 times less likely to be diagnosed with diabetes. The findings from this study have identified a series of potential markers of metabolic disease within the RHAS Maori community. The goal now is to understand how these markers interact with environmental variables to increase the risk of metabolic syndrome. Such an outcome may open the way to designing personalised intervention strategies (e.g. dietary) to increase the health and well-being of at risk individuals.</p>

Haplotype Analysis and Phylogeny of Oryzaephilus surinamensis Populations from Four Regions in Peninsular Malaysia

The sawtoothed grain beetle, Oryzaephilus surinamensis, is a secondary pest that damages rice products and other stored grains. Analysis based on the cytochrome oxidase subunit I (COI) sequences data, the number of haplotypes (Hap) (n), haplotype diversity (Hd), haplotype network, genetic distance, and phylogeny between O. surinamensis populations from four regions (small-scale), viz. the northern area (Seberang Perai), middle area (Klang), southern area (Pasir Gudang), and east coast (Kuantan) of Peninsular Malaysia, as model sampling locations, were obtained. A total of five haplotypes were detected in all the test populations, two shared (Haplotype 1 and Haplotype 3) and three unique haplotypes (Haplotype 2, Haplotype 4, and Haplotype 5) with haplotype diversity value, Hd = 0.6789 were recorded. Furthermore, the neighbour-joining (NJ), maximum parsimony (MP), and Bayesian inference (BI) trees showed a mixture of individuals from all regions in Peninsular Malaysia (Haplotype 1 to Haplotype 4), except Haplotype 5, which was grouped with foreign populations that inherited similar haplotype with those of the European samples. This study assumed a mixture of populations presumably due to human activities and related explicitly to the exportation and importation of rice products across regions. This information is vital for strategising the control management of this pest species to reduce rice storage losses.

Traces of Late Bronze and Early Iron Age Mongolian Horse Mitochondrial Lineages in Modern Populations

The Mongolian horse is one of the most ancient and relatively unmanaged horse breeds. The population history of the Mongolian horse remains poorly understood due to a lack of information on ancient and modern DNA. Here, we report nearly complete mitochondrial genome data obtained from five ancient Mongolian horse samples of the Khereksur and Deer Stone culture (late 2nd to 1st third of the 1st millennium BC) and one ancient horse specimen from the Xiongnu culture (1st century BC to 1st century AD) using target enrichment and high-throughput sequencing methods. Phylogenetic analysis involving ancient, historical, and modern mitogenomes of horses from Mongolia and other regions showed the presence of three mitochondrial haplogroups in the ancient Mongolian horse populations studied here and similar haplotype composition of ancient and modern horse populations of Mongolia. Our results revealed genetic continuity between the Mongolian horse populations of the Khereksur and Deer Stone culture and those of the Xiongnu culture owing to the presence of related mitotypes. Besides, we report close phylogenetic relationships between haplotypes of the Khereksur and Deer Stone horses and the horses of indigenous breeds of the Middle East (Caspian and Iranian), China (Naqu, Yunnan, and Jinjiang), and Italy (Giara) as well as genetic similarity between the Xiongnu Mongolian horses and those of the most ancient breeds of the Middle East (Arabian) and Central Asia (Akhal-Teke). Despite all the migrations of the Mongolian peoples over the past 3000 years, mitochondrial haplogroup composition of Mongolian horse populations remains almost unchanged.

Investigation of RFLP Haplotypes β- Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran

Introduction: Beta-thalassemia is one of the most prevalent inherited blood diseases among Iranians. The aim of this study was to elucidate the chromosomal background of beta-thalassemia mutations in Esfahan province, Iran. Materials and Methods: In this study, we investigated three frequent mutations (c.315+1G>A, c.93-21G>A and c.92+5G>C in β-globin gene, the frequency of RFLP haplotypes, and LD between markers at β-globin gene cluster) in 150 beta-thalassemia patients and 50 healthy individuals. The molecular and population genetic investigations were performed on RFLP markers HindIII in the c.315+1G>A of Gγ (HindIIIG) and Aγ (HindIIIA) genes, AvaII in the c.315+1G>A of β-globin gene and BamHI 3' to the β-globin gene. All statistical analyses were performed using Power Marker software and SISA server. Results: Fifty percent of beta-thalasemia patients were associated with these mutations. Haplotype I was the most prevalent haplotype among beta-thalassemia patients (39.33%) and normal individuals (46%). The commonest c.315+1G>A mutation in our population was tightly linked with haplotype III (43.75%) and haplotype I (31.25%). The second prevalent mutation, c.92+5G>C, was 90%, 6.66%, and 3.33% in linkage disequilibrium with haplotypes I, VII, and III, respectively. The c.93-21G>A mutation indicated a strong association with haplotype I (80%). Conclusion: Our study participants like beta-thalassemia patients from Kermanshah province was found to possess a similar haplotype background for common mutations. The emergence of most prevalent mutations on chromosomes with different haplotypes can be explained by gene conversion and recombination. High linkage of a mutation with specific haplotype is consistent with the hypothesis that chromosomes carrying beta-thalassemia mutations experienced positive selection pressure, probably because of the protection against malaria experienced by beta-thalassemia carriers.

Potential Founder Effect of Tyrosinase Gene Mutations in Oculocutaneous Albinism Families from West of Iran

Background: Non syndromic oculocutaneous albinism type (OCA) is caused by mutations in tyrosinase (TYR), OCA2, TYRP1, MATP (SLC45A2), SLC24A5 and C10ORF11 genes. Screening for mutations is important in families with oculocutaneous albinism patients in order to accurately diagnose the albinism type, genetic counseling and future therapeutic purposes. Objectives: The Aim of this study was to investigate the founder effect of most frequent mutations in OCA patients. Methods: TYR gene was sequenced in 26 unrelated inbred OCA families as well as 56 unrelated healthy individuals. In addition, homozygosity mapping was performed using 13 STR markers for 6 OCA loci (TYR, OCA2, TYRP1, MATP (SLC45A2), SLC24A5 and C10ORF11 genes). Different mutations were found in these genes from which a single base duplication (c.286dupA) and two single base substitutions c.996G > A (p.M332I) and c.230G > A (p.R77Q) had the most frequencies among the OCA families. In order to investigate the founder effect of these mutations, the haplotypes of two STR markers (TYR-S1 and TYR-S2) inside the TYR gene were ascertained. Results: It was revealed that families with similar mutation harbored similar haplotype for the TYR STR markers too. Conclusions: We conclude that these mutations are possible founder mutations in the Iranian population.

Mitochondrial DNA revealed the extent of genetic diversity and invasion origin of populations from two separate invaded areas of a newly invasive pest,Cydia pomonella(L.) (Lepidoptera: Tortricidae) in China

Cydia pomonellais a serious invasive insect pest in China, and has caused severe damage to the production of apple and pear in its invaded areas. This species is distributing in the northwest and northeast of China, but no occurrence of it has been recorded in the large areas (about 3000–5000 km away) between the invaded northwestern and northeastern regions despite continuous monitoring. As yet the genetic diversity and invasion origin of theC. pomonellapopulations in Northwestern and Northeastern China is obscure. In this study, we investigate the genetic diversity of 14 populations ofC. pomonellasampled throughout the main distribution regions in Northwestern (Xinjiang and Gansu Provinces) and Northeastern (Heilongjiang Province) China and compared them with nine populations from Europe and other continents using the mitochondrial COI, COII and Cytb genes. Both the populations from Northeastern and Northwestern China shared some haplotypes with populations from other countries. Haplotypes of the three mitochondrial genes had a different distribution in Northeastern and Northwestern China. The northeastern populations had more private haplotypes than the northwestern populations. A large number of the individuals from northwestern populations shared a few haplotypes of each of the three genes. The haplotype numbers and haplotype diversities of the northeastern populations were similar to those of field populations in other countries, but were higher than those of the northwestern populations. Populations from the Northwestern China showed similar haplotype number and haplotype diversity. We conclude that the population genetic background ofC. pomonellapopulations in Northeastern and Northwestern China varies due to different invasion sources and that this should be considered before the application of new pest control tactics.