Genetic variation of Burgo chicken from Bengkulu, Indonesia, based on the ND1-mitochondrial DNA gene
Burgo chicken Burgo chicken is one of the domesticated red jungle chickens found in Bengkulu Province, Indonesia. Taxonomically, the position of Burgo chicken as a subspecies, species or breed remains unclear due to the lack of supporting data, highlighting the need for further taxonomic identification. We identified two specific sites, 52 and 375, representing single-nucleotide polymorphisms in the ND1 gene, with a gene sequence length of 450bp. Three haplotypes were detected in Burgo chickens, with haplotype 2 shared between Burgo chicken, Gallus gallus (Java) and G. gallus bankiva. The average genetic distance in the Burgo chicken population was 0.1%. When compared to other chicken populations, the average distance was 0.12%, while the distance to other Gallus spp. was 3.62%. All Burgo chickens formed the same clade in the phylogenetic tree, although two individuals (C2F3ND1 and K4F2ND1) showed slight differences. These two individuals were found in Rejang Lebong and Kepahiang, two nearby locations, indicating the possibility that a meeting occurred. Genetic differences within Burgo chickens from Bengkulu, and with other chickens in Indonesia and various parts of the world, were present but not significant. Our data show that Burgo chickens may exhibit differences from other chickens in Indonesia and globally. However, although the genetic data revealed some divergence in mitochondrial DNA, additional morphological and morphometric analyses are needed to provide supporting evidence.
- Research Article
6
- 10.3389/fendo.2023.1093353
- Aug 22, 2023
- Frontiers in Endocrinology
IntroductionPolycystic Ovarian Syndrome (PCOS) is a globally prevalent condition that leads to infertility in women. While environmental factors contribute to PCOS, maternal genetics also play a significant role. Currently, there is no definitive test for identifying predisposition to PCOS. Hence, our objective is to discover novel maternal genetic risk factors for PCOS by investigating the genomes of patients from Pakistan.MethodsWe utilized Next-Generation Sequencing (NGS) to sequence the complete mitochondrial DNA of three PCOS patients. Subsequently, we employed MitoTIP (Mitochondrial tRNA Informatics Predictor) and PON-mt-tRNA tools to identify variations in the mitochondrial DNA. Our analysis focused on the genes MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB, which displayed common variations in all three genomes. Additionally, we observed individual variations. The D-loop region exhibited the highest frequency of mutations, followed by the non-coding regions of RNR1 and RNR2 genes. Moreover, we detected frameshift mutations in the mitochondrially encoded NADH Dehydrogenase 2 (MT-ND2) and mitochondrially encoded NADH Dehydrogenase 5 (ND5) genes within individual genomes.ResultsOur analysis unveiled six regions with common variations in the mitochondrial DNA of all three PCOS patients. Notably, the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes exhibited these variations. Additionally, we identified individual variations in the mitochondrial DNA. The D-loop region displayed the highest mutation frequency, followed by the non-coding regions of RNR1 and RNR2 genes. Furthermore, frameshift mutations were detected in the MT-ND2 and ND5 genes within individual genomes.ConclusionThrough our study, we have identified variations in mitochondrial DNA that may be associated with the development of PCOS and have the potential to serve as predisposition tests. Our findings highlight the presence of novel mutations in the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes, as well as frameshift mutations in the MT-ND2 and ND5 genes. Pathogenicity analysis indicated that most variants were likely to result in benign cysts. However, the frameshift mutations in the ND2 gene were associated with a high risk of complications and pathogenicity in PCOS. This is the first report identifying these mutations and their association with PCOS, contributing to our understanding of the genetic factors underlying the condition.
- Research Article
2
- 10.18517/ijaseit.7.3.1671
- Jun 16, 2017
- International Journal on Advanced Science, Engineering and Information Technology
The research aims to define potential areas for red potato cultivation in agriculture land in Rejang Lebong District, Bengkulu Province, Indonesia. The research was conducted from February to April, 2016 in Rejang Lebong, geographically lying on 102°19'-102°57' Lat., 2°22'07''- 3°31' Long., covering of 155,504.81 ha. Land functions on the district are covered by of Bukit Daun and Bukit Balai Rejang protected forests, Kerinci Seblat National Park, Bukit Kaba Tourism Natural Forest Park, and agricultural cultivation areas. To define land suitability for red potato cultivation in Rejang Lebong areas based on suitable temperature following adaptation experiment results of red potato planted in the medium altitude of Bengkulu Province conducting previously. Spatial analysis for calculating areas of potential suitable cultivation for red potato was based on overlaying from attributes of suitable temperature, rainfall, and some soil characteristics. Initial suitable land for potato plantation in Rejang Lebong covered about ha 46,608.98 ha or 29.97 % of the district area with agriculture land function of 11,954.59 ha or 7.69% of the district, and forest land use of 34,654.39 ha or 22.28% of the district. Based on the overlying suitable land for red potato cultivation over the Rejang Lebong areas was about 108,639.36 ha lying on agriculture land use of 58,076.64 ha or 37.34%, and over on conservation and protected forest of 50,562.72 ha or 32.51%. Potential suitable land for potato cultivation in Rejang Lebong after correcting with reference of suitable temperature covered double more of the agriculture land than that of the initial. Therefore, in one hand, Rejang Lebong as a central of potato production in Bengkulu has some opportunities to increase potato production for supplying potato demand from surrounding areas in the future. On the other, attempt to increase potato production in Rejang Lebong have to consider environmental aspects and protected conservation forest areas.
- Research Article
- 10.1080/00071668.2025.2601730
- Jan 19, 2026
- British Poultry Science
1. This study investigated the maternal lineage and genetic diversity of indigenous Indonesian chickens using mitochondrial DNA (mtDNA) D-loop sequences to assess population structure and maternal origins. 2. Fifty-two samples from eight chicken populations were sequenced for the 1231 bp mtDNA D-loop region. A total of 26 haplotypes were identified, with high diversity observed across all populations (Hd = 0.700–0.933). Most chickens, including Tukong, clustered in haplogroup D1, which suggested a shared maternal lineage common to Southeast Asian domesticated chickens. Two individuals (KUB2 and TK2) were positioned in sub-haplogroup D2, indicating sequence divergence. Merawang and Nunukan chickens were grouped into haplogroups A and B, respectively, consistent with haplotypes shared with Chinese and Japanese chickens, pointing to historical maternal introgression, likely via trade or migration. Analysis of molecular variance (AMOVA) revealed that 28.45% of genetic variation existed among populations (Fst = 0.284, p < 0.001), which indicated a moderate but statistically significant population structure. 3. Multiple haplogroups in Indonesian chickens reflect complex maternal origins and past gene flow from outside populations. These findings highlighted the importance of understanding genetic structure to inform the management and characterisation of native breeds. The distinct maternal lineages in Merawang and Nunukan showed historical introductions, while the close relationship among Tukong and Kampung chickens implied interbreeding under extensive rearing systems.
- Research Article
1
- 10.18502/jad.v16i2.11799
- Jan 31, 2023
- Journal of Arthropod-Borne Diseases
Androctonus crassicauda is the most medically relevant scorpion and understanding its genetic forms is essential for improvement of anti-venom sera, and risk management of scorpionism. Present study was designed to identify the variations of mitochondrial genes in different populations of A. crassicauda. Adults of A. crassicauda were collected from Zanjan Province during 2016-2017. Genomic DNA of samples was extracted and fragments of mitochondrial 16S, COI and ND1 genes were amplified and some of the amplicons were sequenced. Haplotype of samples were identified by multiple alignment of sequences, then phylogenetic trees of haplotypes were constructed. Fragments of 352bp, 618bp and 680bp were amplified from 16S, COI and ND1 genes respectively. Nucleotide sequence in COI fragments was conserved, however, five haplotypes with some specific polymorphic sites were detected in 16S and ND1 fragments. Haplotype I was dominant and found in all areas. Other haplotypes were rare and limited to specific regions. Analysis of the phylogenetic trees inferred from 16S and COI genes, confirmed a strong positive correlation between geographic and genetic distance. Mitochondrial COI, 16S and ND1 genes were detected suitable for identifying the population structure. Five genotypes were found using 16S and ND1 genes. To prepare and improve the anti-venoms quality, additional studies are necessary to identify the toxin electrophoretic profile and geographical/ecological niche models of these genotypes in future.
- Research Article
90
- 10.1016/s1525-1578(10)60553-3
- May 1, 2005
- The Journal of Molecular Diagnostics
Mitochondrial DNA as a Cancer Biomarker
- Research Article
26
- 10.1111/j.1365-294x.2008.03845.x
- Jul 1, 2008
- Molecular Ecology
Daubenton's bat (Myotis daubentonii) is a known reservoir for European bat lyssavirus type 2 (EBLV-2). An appreciation of the potential for epidemiological spread and disease risk requires an understanding of the dispersal of the primary host, and any large-scale geographical barriers that may impede gene flow. The spatial pattern of microsatellite and mitochondrial DNA variation was examined to infer patterns of dispersal of bats among 35 populations across Scotland. DNA sequence variation at the mitochondrial control region and ND1 genes revealed two distinct phylogeographical clades, with generally nonoverlapping geographical distributions except for a small number of populations where both matrilines were found in sympatry. Such discontinuity suggests that Scotland was recolonized twice following the retreat of the Pleistocene ice sheet with little subsequent matrilineal introgression. However, eight microsatellite loci showed low levels of genetic divergence among populations, even between populations from the two distinct mitochondrial DNA clades. An overall, macrogeographical genetic isolation-by-distance pattern was observed, with high levels of gene flow among local populations. Apparently contrasting patterns of mitochondrial and microsatellite divergence at different scales could be explained by sex-specific differences in gene flow at large scales.
- Research Article
2
- 10.14334/jitv.v17i2.686
- May 8, 2013
- Jurnal Ilmu Ternak dan Veteriner
Until now no studies evaluating the position of Kampung chickens in chicken clade of Asia. Thus studies based on molecular DNA sequence hipervariable-I on Kampung chicken is needed. Molecular studies based on DNA sequences hyper variable-I of Kampong chicken was done to confirm the results of previous evaluations conducted on 15 families of local chickens of Indonesia. An analysis of 210 individuals Kampung chicken (Aceh, North Sumatra, Lampung, Banten, Central Java, Lombok, Sulawesi, Ternate, Morotai and Halmahera) resulted in 51 haplotypes derived from 62 polymorphic sites. Polymorphic sites among the highest seen at 112-397 (93.22%). The highest haplotype frequencies contained in the haplotype H-4 (36.19%), followed by H-1 (18.57%) and H-5 (10, 95%). Kampung chicken phylogeny analysis formed four haplogroups/clade from 7 references of Asian chicken clade. Four haplogroups are clade II = 84.31% (43 haplotypes), clade IIIC = 1.96% (1 haplotype), clade IIID = 3.92% (2 haplotypes), clade IV = 7.84% (4 haplotypes). The results prove of that Indonesian local and indigenous chickens were equally dominated clade II. Analysis of genetic diversity showed haplotype diversity of 0.825 ± 0.021, nucleotide diversity of 0.00600 on average, the genetic distance between populations ranged from 0.003 to 0.011, and the genetic distance within populations ranged from 0.00395 to 0.01031. Genetic distance between individuals in all populations of Kampung chickens was significantly different (P 0.01). Fu's Fs values was negative, indicating high genetic diversity and population expansion on native chicken in Indonesia. Other important result was shown with the major haplotype spread from western to eastern Indonesia, and had strengthened the position of Indonesia as one of the centers of domestication of the chicken. Key Words: Kampung Chicken, Hypervariable-I, Control Region, Mitochondrial DNA, Haplotype, Clade
- Supplementary Content
5
- 10.1016/j.ymgmr.2024.101183
- Dec 28, 2024
- Molecular Genetics and Metabolism Reports
Mitochondrial DNA variants in the pathogenesis and metabolic alterations of diabetes mellitus
- Research Article
6
- 10.18502/kls.v2i6.1026
- Nov 26, 2017
- KnE Life Sciences
Animal genetic resources such as indigenous chickens are part of biodiversity. Sentul chickens are one of indigenous chickens in Indonesia which are regarded as local to Ciamis District in West Java. It is reported that the population of pure Sentul Chickens are in decline. This study was aimed to find out the current population of pure Sentul chickens in three areas in West Java and to develop a conservation strategy to safeguard Sentul chickens in the future. The study used qualitative method to gather data including literature review and key informant interviews. The informants consisted of a leader of farmer group and managers of breeding centers. The interviews were carried out in Ciamis, Majelengka and Bogor Districts. The data were analyzed by descriptive analysis. The results indicated that population of Sentul chickens in Ciamis are in decline, while population in areas outside Ciamis such as Bogor tend to increase. There is a need to develop an in-situ conservation program in which Ciamis District should be assigned to be the center area to provide pure Sentul chickens in West Java. To support the conservation program, stakeholders such as local government, research institutions, universities and farmer groups play important roles. Keywords: in-situconservation strategy, Sentul chickens, animal genetic resources, biodiversity.
- Research Article
- 10.3760/cma.j.issn.2095-4255.2018.07.004
- Jul 20, 2018
Objective To make up the limitations of traditional morphological classification methods, we identified vector fleas by DNA barcoding in Qinghai Province. Methods The mt DNA cytochrome c oxidase subunit Ⅰ(COⅠ) gene was amplified by PCR from 36 muscle tissues of fleas in 3 states, 2 cities and 5 counties of Qinghai Province, and the obtained COⅠ gene fragments were sequenced and aligned. The intra- and inter-species genetic distances were calculated with Mega 6 software using K2-P model and a phylogenetic tree was constructed with neighbor-joining (NJ) method. Results Totally 36 COⅠ gene sequences of 2 superfamilies, 4 genera and 6 kinds of vector fleas were measured, the average genetic distance was 0.119, and the intraspecific distance was 0.002 - 0.027, the interspecific distance was 0.039 - 0.207, and the interspecific genetic distance was significantly greater than the intraspecific genetic distance. NJ tree showed the same species had formed a single line with high support rate and interspecific branch was clear. Conclusion DNA barcoding is suitable for identification of vector fleas in Qinghai Province, may make up the limitations of traditional morphological classification methods. Key words: Siphonaptera; Cytochrome c oxidase subunit Ⅰ; DNA barcoding
- Research Article
- 10.33369/tmr.v4i2.25845
- Dec 31, 2022
- The Manager Review
:
 The objectives of this research is the (1) To find out the company's strategic response in responding to the BRTI regulations number 01 of 2018, (2) To find out the response to the r strategy. This study uses qualitative methods, respondents research is the leadership of PT. Telkomsel Tbk, PT.Indosat Tbk, PT. TRI Tbk, PT.XL AxiataTbk and 25 Retail Outlets, each taken 5 from the city of Bengkulu, kab. Bengkulu Tengah, Kab. Kepahiang, Kab. Rejang Lebong, Kab. Lebong, with a population of 1362 retail outlets in Bengkulu province, then 25 retail outlets were taken to be used as samples, the sampling technique used the Non Probability Sampling method with purposive sampling technique, this study was conducted by interviewing 29 samples, data collection techniques using the interview method, while The data analysis used is descriptive data analysis. The results of this study are A. The Company's Strategic Response to the BRTI Policy No. 01 of 2018 1. The response of telecommunications service providers as a whole can be concluded positively that the BRTI policy Number 01 of 2018 can reduce crime through telecommunications services, but the impact felt by the implementation of this policy is the decline in sales of starter packs, this is due to registration restrictions starter packs and this makes selling starter packs difficult. 2. The company's strategies or efforts to increase sales of starter packs in the form of price discounts, rewards, sp bundling programs, CSO teams by picking up the ball and also launching new products with more bonuses for consumers, but the policies or strategies that have been issued have not had a significant impact on the increase in sales of starter packs, this is because customers are still complaining about the difficulty of registering a starter pack by having to submit a family card which is limited to 1 NIK which can only be registered for 3 numbers. B. Retail Outlet Strategy Response to BRTI Policy No. 01 Year 2018, (1) Retail outlets said that the BRTI policy No. 01 of 2018 concerning restrictions on registration of 1 Nik starter packs can only be 3. This number can reduce crime, but based on what is currently happening, criminal acts through telecommunications media are still happening even though the policy of limiting registration and being registered must be according to customer data, it has been implemented, sales of starter packs have decreased significantly and there are even cards that have expired so that respondents experience losses, (2) Retail outlet strategy as a whole they sell starter packs at low prices and there are also retail outlets that provide education to customers on how to register starter packs and there are also outlets that make regular offers related to starter pack products to consumers by explaining the advantages of the starter pack itself, however, in terms of sales of starter packs, there has not been an increase, there are even retail outlets who say that no matter what strategy they take while restrictions on registration of starter packs are still in effect, selling starter packs is still difficult. This research is inseparable from limitations and weaknesses, on the other hand the limitations and weaknesses found in this study can be used as a source of ideas for future research. The limitations found in this study were that the sample used in this study was only 4 companies providing telecommunications services in Prov. Bengkulu and 25 Retail Outlets taken each 5 retail outlets in Bengkulu City, Kab. Central Bengkulu, Kab. Kepahiang, Kab. Rejang Lebong, Kab. Lebong.
 Keywords: Response, Strategy, Company, Retail Outlet, BRTI Policy No. 01 Year 2018
 Abstrak :
 Tujuan dari penelitian ini adalah (1) Untuk mengetahui respon strategis perusahaan dalam menyikapi peraturan BRTI nomor 01 Tahun 2018, (2) Untuk mengetahui respon terhadap strategi r. Penelitian ini menggunakan metode kualitatif, responden penelitian adalah pimpinan PT. Telkomsel Tbk, PT.Indosat Tbk, PT. TRI Tbk, PT.XL AxiataTbk dan 25 Retail Outlet masing-masing diambil 5 dari kota Bengkulu, kab. Bengkulu Tengah, Kab. Kepahiang, Kab. Rejang Lebong, Kab. Lebong dengan populasi 1362 gerai di provinsi Bengkulu, maka diambil 25 gerai untuk dijadikan sampel, teknik pengambilan sampel menggunakan metode Non Probability Sampling dengan teknik purposive sampling, penelitian ini dilakukan dengan mewawancarai 29 sampel, pengumpulan data tekniknya menggunakan metode wawancara, sedangkan analisis data yang digunakan adalah analisis data deskriptif. Hasil dari penelitian ini adalah A. Respon Strategis Perusahaan Terhadap Kebijakan BRTI No. 01 Tahun 2018 1. Respon penyelenggara jasa telekomunikasi secara keseluruhan dapat disimpulkan positif bahwa kebijakan BRTI No. 01 Tahun 2018 dapat menekan kejahatan melalui jasa telekomunikasi , namun dampak yang dirasakan dari pemberlakuan kebijakan tersebut adalah menurunnya penjualan kartu perdana, hal ini dikarenakan adanya pembatasan pendaftaran paket perdana dan hal ini membuat penjualan paket perdana menjadi sulit. 2. Strategi atau upaya perusahaan dalam meningkatkan penjualan starter pack berupa potongan harga, reward, program sp bundling, tim CSO dengan jemput bola dan juga launching produk baru dengan bonus yang lebih banyak untuk konsumen, namun kebijakan atau strategi yang telah dikeluarkan belum memberikan dampak yang signifikan terhadap peningkatan penjualan kartu perdana, hal ini dikarenakan pelanggan masih mengeluhkan sulitnya pendaftaran kartu perdana dengan harus menyerahkan kartu keluarga yang dibatasi hanya 1 NIK yang hanya dapat terdaftar untuk 3 nomor. B. Strategi Gerai Ritel Menanggapi Kebijakan BRTI No. 01 Tahun 2018, (1) Gerai Ritel menyampaikan bahwa kebijakan BRTI No. 01 Tahun 2018 tentang pembatasan pendaftaran 1 paket perdana Nik hanya boleh 3. Jumlah ini dapat menekan angka kriminalitas, namun berdasarkan yang terjadi saat ini, tindak pidana melalui media telekomunikasi masih terjadi walaupun kebijakan pembatasan pendaftaran dan pendaftaran harus sesuai dengan data pelanggan, sudah diterapkan, penjualan kartu perdana mengalami penurunan yang signifikan bahkan ada kartu kadaluarsa sehingga responden mengalami kerugian, (2) Strategi gerai retail secara keseluruhan mereka menjual kartu perdana dengan harga murah dan ada juga gerai ritel yang memberikan edukasi kepada pelanggan cara pendaftaran paket perdana dan ada juga gerai yang melakukan penawaran berkala terkait produk paket perdana kepada konsumen dengan cara menjelaskan kelebihan dari kartu perdana itu sendiri, namun dari segi penjualan kartu perdana belum ada peningkatan, bahkan ada retailer yang mengatakan bahwa apapun strategi yang mereka ambil sementara pembatasan pendaftaran kartu perdana masih dalam efeknya, jualan starter pack masih susah. Penelitian ini tidak terlepas dari keterbatasan dan kelemahan, di sisi lain keterbatasan dan kelemahan yang ditemukan dalam penelitian ini dapat dijadikan sebagai sumber ide untuk penelitian selanjutnya. Keterbatasan yang ditemukan dalam penelitian ini adalah sampel yang digunakan dalam penelitian ini hanya 4 perusahaan penyedia jasa telekomunikasi di Prov. Bengkulu dan 25 Gerai Diambil masing-masing 5 Gerai di Kota Bengkulu Kab. Bengkulu Tengah, Kab. Kepahiang, Kab. Rejang Lebong, Kab. Lebong.
 Kata kunci: Respons, Strategi, Perusahaan, Gerai Ritel, Kebijakan BRTI No. 01 Tahun 2018
- Research Article
2
- 10.18343/jipi.27.4.574
- Oct 25, 2022
- Jurnal Ilmu Pertanian Indonesia
Chili is one of the horticultural commodities with increasing demand yearly. Rejang Lebong and Kepahiang regencies are the most significant chili-producing areas in Bengkulu. One of the crucial viruses in chili plants is Pepper yellow leaf curl virus (PYLCV). PYLCV virus infection in the vegetative phase can cause stunted plants and fail to bear fruit. This study aims to detect and genetically characterize PYLCV. Samples of chili plants were taken in these two districts using the purposive sampling method. Virus detection was carried out at the Genetics and Biotechnology Laboratory, Department of Biology. Extraction of viral DNA using the Cetyl Trimethyl Ammonium Bromide (CTAB) method. Rep and Trap gene amplification using universal primers of Bemovirus. SPG1 and SPG2. The PCR product was visualized on a 1.2% agarose gel in TAE.. Furthermore, the PCR products were sequenced in PT Genetics Science Indonesia. Virus gene sequences were aligned using Bioedit and MEGA X software. The results showed that of the 24 chili plants sampled in the study, 21 samples showed an amplicon with a size of ~ 900 bp, which follows the length of the amplicon based on the primer used. Of the 21 amplicon results, 6 of them were sequenced and genetically characterized. The results of the genetic characterization of the 6 samples showed the presence of 552 conservative sites (C) (75.6%), 178 variation sites (Vi) (24.4%), parsimony sites (Pi) (15.9%), and 70 singleton (S) sites (8.5%). The highest nucleotide base composition was thymine (T) with an average value of 30.1%, and the lowest was guanine (G) 21.9%, while the highest nucleotide combined composition was AT with an average value of 55%, the lowest was GC approximately 45%. The average genetic distance between samples was 0.13 (13%). Based on the phylogenetic tree, 6 samples were divided into two groups. Keywords: begomovirus, Bengkulu, Capsicum annuum
- Research Article
- 10.1088/1742-6596/2596/1/012039
- Sep 1, 2023
- Journal of Physics: Conference Series
Rejang Lebong is a regency in the province of Bengkulu, located in the Bukit Barisan mountainous region. The area is dominated by fault earthquakes due to its proximity to the Musi and Ketaun faults. This article presents the results of a study on earthquake hazard analysis through microtremor measurement using the HVSR method to determine the value of Peak Ground Acceleration (PGA). Measurements were taken at 10 points for 60 minutes with a 2 km interval. The HVSR method was used to obtain the dominant period value. The determination of PGA value was based on historical fault earthquakes in RejangLebong in 1943 with a magnitude of Mw 7.4. The largest PGA value obtained was 627.34 gal, which was in the western part of the study area. This is significantly correlated with the earthquake hazard in 1943, which caused the highest damage in the Tes village located in the western part of the study area. This research is useful for pre-disaster earthquake mitigation plans through risk management to reduce the impact of earthquake hazards.
- Research Article
16
- 10.3892/br.2019.1250
- Nov 4, 2019
- Biomedical Reports
Multiple sclerosis (MS) is an immune-mediated neurological, inflammatory disease of the central nervous system. Recent studies have suggested that genetic variants in mitochondrial DNA (mtDNA)-encoded complexes of respiratory chain, particularly, complex I (NADH dehydrogenase), contribute to the pathogenicity of MS among different ethnicities, and targeting mitochondrial function may represent a novel approach for MS therapy. In this study, we sequenced ND genes (ND1, ND2, ND3, ND4, ND4L, ND5 and ND6) encoding subunits of complex I in 124 subjects, 60 patients with relapsing-remitting MS and 64 healthy individuals, in order to identify potential novel mutations in these patients. We found several variants in ND genes in both the patients and controls, and specific variants only in patients with MS. While the majority of these variants were synonymous, 4 variants in the ND4 gene were identified as missense mutations in patients with MS. Of these, m.11150G>A was observed in one patient, whereas m.11519A>C, m.11523A>C and m.11527C>T were observed in another patient. Functional analysis predicted the mutations, m.11519A>C, m.11523A>C and m.11150G>A, as deleterious with a direct impact on ND4 protein stability and complex I function, whereas m.11527C>T mutation had no effect on ND4 protein stability. However, the 3 mutations, m.11519A>C, m.11523A>C and m.11527C>T, which were observed in the same patient, were predicted to cause a cumulative destabilizing effect on ND4 protein, and could thus disrupt complex I function. On the whole, this study identified 4 novel mutations in the mtDNA-encoded ND4 gene in patients with MS, which could lead to complex I dysfunction, and further confirmed the implication of mtDNA mutations in the pathogenicity of MS. The identified novel mutations in patients with MS may be ethnic-related and may prove to be significant in personalized treatment.
- Research Article
134
- 10.1002/ajp.20094
- Jan 1, 2005
- American Journal of Primatology
DNA was extracted from the buffy coats or serum of 212 rhesus macaques (Macaca mulatta) sampled throughout the species' geographic range. An 835 base pair (bp) fragment of mitochondrial DNA (mtDNA) was amplified from each sample, sequenced, aligned, and used to estimate genetic distances from which phylogenetic trees were constructed. A tree that included sequences from rhesus macaques whose exact origins in China are known was used to determine the regional origin of clusters of haplotypes, or haplogroups, defined by the trees. Indian rhesus sequences formed one large homogeneous haplogroup with very low levels of nucleotide diversity and no geographic structure, and a second much smaller haplogroup apparently derived from Burma. The sequences from Burma and eastern and western China were quite divergent from those in the major haplogroup of India. Each of these sequences formed separate clusters of haplotypes that exhibited far greater nucleotide diversity and/or population structure. Correspondingly, sequences from Indian rhesus macaques that are considered to represent different subspecies (based on morphological differences) were intermingled in the tree, while those from China reflected some, but not all, aspects of subspecific taxonomy. Regional variation contributed 72% toward the paired differences between sequences in an analysis of molecular variance (AMOVA), and the average differences between the populations of eastern and western China were also statistically significant. These results suggest that Indian and Chinese rhesus macaques were reproductively isolated during most, if not all, of the Pleistocene, during which time Indian rhesus macaques experienced a severe genetic bottleneck, and that some gene flow westward into India was subsequently reestablished. Samples from breeding centers in three different provinces of China included sequences from rhesus macaques that originated in both eastern (or southern) and western China, confirming anecdotal reports that regional breeding centers in China exchange breeding stock. Genetic differences among rhesus macaques (even those acquired from the same regional breeding center) that originate in different geographic regions and are employed as subjects in biomedical experiments can contribute to phenotypic differences in the traits under study.
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