mtDNA Haplogroups Research Articles

Differential effects of cisplatin on cybrid cells with varying mitochondrial DNA haplogroups.

BackgroundDrug therapy yields different results depending on its recipient population. Cisplatin, a commonly used chemotherapeutic agent, causes different levels of resistance and side effects for different patients, but the mechanism(s) are presently unknown. It has been assumed that this variation is a consequence of differences in nuclear (n) DNA, epigenetics, or some external factor(s). There is accumulating evidence that an individual’s mitochondrial (mt) DNA may play a role in their response to medications. Variations within mtDNA can be observed, and an individual’s mtDNA can be categorized into haplogroups that are defined by accumulations of single nucleotide polymorphisms (SNPs) representing different ethnic populations.MethodsThe present study was conducted on transmitochondrial cytoplasmic hybrids (cybrids) that possess different maternal-origin haplogroup mtDNA from African (L), Hispanic [A+B], or Asian (D) backgrounds. Cybrids were created by fusing Rho0 ARPE-19 cells (lacking mtDNA) with platelets, which contain numerous mitochondria but no nuclei. These cybrid cells were cultured to passage five, treated with cisplatin, incubated for 48 h, then analyzed for cell metabolic activity (tetrazolium dye (MTT) assay), mitochondrial membrane potential (JC-1 assay), cytotoxicity (lactate dehydrogenase (LDH) assay), and gene expression levels for ALK, BRCA1, EGFR, and ERBB2/HER2.ResultsResults indicated that untreated cybrids with varying mtDNA haplogroups had similar relative metabolic activity before cisplatin treatment. When treated with cisplatin, (1) the decline in metabolic activity was greatest in L (27.4%, p < 0.012) < D (24.86%, p = 0.0001) and [A+B] cybrids (24.67%, p = 0.0285) compared to untreated cybrids; (2) mitochondrial membrane potential remained unchanged in all cybrids (3) LDH production varied between cybrids (L >[A+B], p = 0.0270). (4) The expression levels decreased for ALK in L (p < 0.0001) and [A+B] (p = 0.0001) cybrids but not in D cybrids (p = 0.285); and decreased for EGFR in [A+B] cybrids (p = 0.0246) compared to untreated cybrids.ConclusionOur findings suggest that an individual’s mtDNA background may be associated with variations in their response to cisplatin treatment, thereby affecting the efficiency and the severity of side effects from the treatment.

Associations of mitochondrial genomic variation with corticobasal degeneration, progressive supranuclear palsy, and neuropathological tau measures

Mitochondrial health is important in ageing and dysfunctional oxidative phosphorylation (OXPHOS) accelerates ageing and influences neurodegeneration. Mitochondrial DNA (mtDNA) codes for vital OXPHOS subunits and mtDNA background has been associated with neurodegeneration; however, no study has characterised mtDNA variation in Progressive supranuclear palsy (PSP) or Corticobasal degeneration (CBD) risk or pathogenesis. In this case–control study, 910 (42.6% male) neurologically-healthy controls, 1042 (54.1% male) pathologically-confirmed PSP cases, and 171 (52.0% male) pathologically-confirmed CBD cases were assessed to determine how stable mtDNA polymorphisms, in the form of mtDNA haplogroups, were associated with risk of PSP, risk of CBD, age of PSP onset, PSP disease duration, and neuropathological tau pathology measures for neurofibrillary tangles (NFT), neuropil threads (NT), tufted astrocytes (TA), astrocytic plaques (AP), and oligodendroglial coiled bodies (CB). 764 PSP cases and 150 CBD cases had quantitative tau pathology scores. mtDNA was genotyped for 39 unique SNPs using Agena Bioscience iPlex technologies and mitochondrial haplogroups were defined to mitochondrial phylogeny. After adjustment for multiple testing, we observed an association with risk of CBD for mtDNA sub-haplogroup H4 (OR = 4.51, P = 0.001) and the HV/HV0a haplogroup was associated with a decreased severity of NT tau pathology in PSP cases (P = 0.0023). Our study reports that mitochondrial genomic background may be associated with risk of CBD and may be influencing tau pathology measures in PSP. Replication of these findings will be important.

Reduced mitochondrial DNA copy number is associated with the haplogroup, and some clinical features of breast cancer in Mexican patients.

Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p=0.010); it was significantly decreased in BCT and NAT in women>50years of age, compared with NAT in women<50years of age (p=0.032 and p=0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p=0.011, p=0.010 and, p=0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p=0.025, p=0.022 and p=0.031 and p=0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p=0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p=0.006) and with BCT patients belonging to haplogroups A2 and D1 (p=0.01 and p=0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p=0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p=0.021, =0.048, and=0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.

Mitochondrial genome variation in male LHON patients with the m.11778G\u2009>\u2009A mutation

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of cases it is caused by one of three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and ~10% women who carry them are affected. Thus additional modifying factors must exist. In this study, we use next generation sequencing to investigate the role of whole mtDNA variation in male Polish patients with LHON and m.11778G > A, the most frequent LHON mutation. We present a possible association between mtDNA haplogroup K and variants in its background, a combination of m.3480A > G, m.9055G > A, m.11299 T > C and m.14167C > T, and LHON mutation. These variants may have a negative effect on m.11778G > A increasing its penetrance and the risk of LHON in the Polish population. Surprisingly, we did not observe associations previously reported for m.11778G > A and LHON in European populations, particularly for haplogroup J as a risk factor, implying that mtDNA variation is much more complex. Our results indicate possible contribution of novel combination of mtDNA genetic factors to the LHON phenotype.

Genetic diversity and structure of circumtropical almaco jack, Seriola rivoliana: tool for conservation and management.

The almaco jack, Seriola rivoliana, is a circumtropical pelagic fish of importance both in commercial fisheries and in aquaculture. To understand levels of genetic diversity within and among populations in the wild, population genetic structure and the relative magnitude of migration were assessed using mtDNA sequence data and single nucleotide polymorphisms (SNPs) from individuals sampled from locations in the Pacific and Atlantic Oceans. A total of 25 variable sites of cytochrome c oxidase subunit 1 and 3678 neutral SNPs were recovered. Three genetic groups were identified, with both marker types distributed in different oceanic regions: Pacific-1 in central Pacific, Pacific-2 in eastern Pacific and Atlantic in western Atlantic. Nonetheless, the analysis of SNP identified a fourth population in the Pacific coast of Baja California Sur, Mexico (Pacific-3), whereas that of mtDNA did not. This mito-nuclear discordance is likely explained by a recently diverged Pacific-3 population. In addition, two mtDNA haplogroups were found within the western Atlantic, likely indicating that the species came into the Atlantic from the Indian Ocean with historical gene flow from the eastern Pacific. Relative gene flow among ocean basins was low with r m < 0.2, whereas in the eastern Pacific it was asymmetric and higher from south to north (r m > 0.79). The results reflect the importance of assessing genetic structure and gene flow of natural populations for the purposes of sustainable management.

Mitochondrial DNA haplogroup H association with endometriosis and possible role in inflammation and pain

Introduction: Endometriosis is an inflammatory disease characterised by the presence of endometrial-like tissue outside the uterus and affects approximately 10%–15% of women in their reproductive years. Pain is one of the predominant symptoms of the disease. Oxidative stress is involved in the pathophysiology of endometriosis and develops when there is an imbalance between the reactive oxygen species and reactive nitrogen species production, and the elimination capacity of antioxidants in the reproductive tract. High levels of reactive oxygen species can induce pain indirectly through oxidative stress-associated inflammation or directly through sensitising the nociceptive neurons that transmit the signals to the cerebral sensory cortex which are perceived as a feeling of pain. Mitochondria are the main source of reactive oxygen species, which generate through oxidative phosphorylation. Given that the mitochondria are involved in reactive oxygen species formation and energy production, which are required for the activation and proliferation of peripheral lymphocytes, it has been suggested that mitochondrial DNA variants are involved in the pathogenesis of endometriosis. This study has provided a better understanding of maternally inherited risk factors which contribute to the pain mechanisms associated with endometriosis. Results: Mitochondrial DNA haplogroup H was found to be significantly higher in women with endometriosis. This study was the first to report the association between the European mitochondrial haplogroup H and the risk of pain associated with endometriosis. Discussion: The results suggest that there are maternally inherited risk factors in women with endometriosis causing high reactive oxygen species production and oxidative stress, which facilitate pain generation in women with endometriosis.

Mitochondrial Haplogroup Reveals the Genetic Basis of Diabetes Mellitus Type 2 Comorbidity in Psoriasis

Objective: Published data show a clear link between psoriasis (Ps) and the increasing prevalence of comorbid conditions, such as diabetes mellitus type 2 (DM2). The role of the mitochondrial genomic haplogroup in the potential coexistence of Ps and DM2 comorbidity is the subject of this study. Material and Methods: Ninety-eight Kuwaiti individuals were recruited in 4 cohorts (20 healthy controls, 15 with DM2, 34 with Ps, and 29 with Ps and diabetes mellitus). An Ion Torrent S5XL was used to sequence mitochondrial DNA (mtDNA). χ² test was used to assess differences in the distribution of each haplogroup between cases and controls (p < 0.05). The Bonferroni correction was applied (p < 0.004). The mtDNA haplogroups were analyzed by HaploGrep. Results: Haplogroups R0, U, J, T, N, L3, M, H, X, HV, R, and K were detected in the studied population. Haplogroup M had a high risk for Ps (odds ratio (OR) 4.0, p = 0.003). Haplogroup R0 and J had decreased the risk of DM2 (OR 0.28, p = 0.007). Conclusion: Our results indicated that mtDNA haplogroups have a potential contribution to the pathogenesis of Ps and DM2 comorbidity. We show for the first time that the comorbidity of diabetes in Ps may be related to mitochondrial dysfunction.

Lack of association between mitochondrial DNA haplogroups J and T and clinical manifestation in Russian patients with Brugada syndrome.

Brugada syndrome (BrS) is an inherited disorder characterized by specific ST segment elevation in the right precordial leads, pseudo right bundle branch block, and a high risk of sudden cardiac death due to ventricular tachycardia. It was initially described as a monogenic disorder with an autosomal dominant mode of inheritance. It is hypothesized that modifying genetic factors, in addition to disease-causing mutations, may significantly contribute to the clinical symptoms and the risk of sudden cardiac death. These modifying factors can include mitochondrial DNA (mtDNA) variants. In particular, combination of mtDNA m.T4216C, m.A11251G, m.C15452A and m.T16126C variants (defining haplogroups T and J), is considered to be a factor that promotes manifestation of BrS manifestation, with no pro-arrhythmic effects. The aim of the present study was to confirm the reported association of BrS with MtDNA variants in a cohort of Russian patients. mtDNA haplogroups were genotyped in 47 Russian BrS probands and the prevalence of common mtDNA haplogroups was compared with the general population in European part of Russia. The distribution and prevalence of all but the J mtDNA haplogroups were comparable in BrS probands and the general Russian population. The mitochondrial J haplogroup was not found in the BrS cohort. In conclusion, it was shown that the mtDNA polymorphism, m.T4216C (haplogroups J and T) does not contribute significantly to the clinical manifestation of BrS in Russian patients.

Analysis of Asian Mitochondrial DNA Haplogroups Associated With the Progression of Knee Osteoarthritis in Koreans

Bon San Koo, M.D., Yoonah Song, M.D., Seunghun Lee, M.D., Ph.D., Yoon-Kyoung Sung, M.D., Ph.D., Kyoung-Jin Shin, M.D., Ph.D., Nam H. Cho, M.D., Ph.D., Jae-Bum Jun, M.D., Ph.D.. J Rheum Dis 2020;27:168-73. https://doi.org/10.4078/jrd.2020.27.3.168

Evolutionary dissection of mtDNA hg H: a susceptibility factor for hypertrophic cardiomyopathy

Mitochondrial DNA (mtDNA) haplogroup (hg) H has been reported as a susceptibility factor for hypertrophic cardiomyopathy (HCM). This was established in genetic association studies, however, the SNP or SNP’s that are associated with the increased risk have not been identified. Hg H is the most frequent European mtDNA hg with greater than 80 subhaplogroups (subhgs) each defined by specific SNPs. We tested the hypothesis that the distribution of H subhgs might differ between HCM patients and controls. The subhg H distribution in 55 HCM index cases was compared to that of two Danish mtDNA hg H control groups (n = 170 and n = 908, respectively). In the HCM group, H and 12 different H subhgs were found. All these, except subhgs H73, were also found in both control groups. The HCM group was also characterized by a higher proportion of H3 compared to H2. In the HCM group the H3/H2 proportion was 1.7, whereas it was 0.45 and 0.54 in the control groups. This tendency was replicated in an independent group of Hg H HCM index cases (n = 39) from Queensland, Australia, where the H3/H2 ratio was 1.5. In conclusion, the H subhgs distribution differs between HCM cases and controls, but the difference is subtle, and the understanding of the pathogenic significance is hampered by the lack of functional studies on the subhgs of H.

Identification of Ajnala skeletal remains using multiple forensic anthropological methods and techniques: A bioarchaeological report

Fragmented and badly damaged commingled human remains present a tough challenge for their identification pursuits in forensic anthropology. Thousands of unknown human remains along with items of contextual identity, reportedly belonging to 282 Indian sepoys killed in 1857, were exhumed mon-scientifically from a disused ancient well at Ajnala (Amritsar, India). In this manuscript, the non-scientific excavation of unknown human remains from the abandoned well, their forensic anthropological strategies for identification purposes, challenges being faced and future possibilities of their biological profiling have been discussed. Multiple methods and techniques like anthropological examinations, odontological profiling, radiological analyses, stable isotope and mitochondrial DNA (mtDNA) analyses were applied to few bones and teeth collected from the Ajnala skeletal assemblage. Though majority of studied bones and teeth were found belonging to adult males, very few of them had morphological, osteological and molecular features questioning the authenticity and validity of the written records. Due to certain ambiguous findings or gaps observed between the anthropological analyses of the Ajnala skeletal remains and the reported versions about their affiliations; certain advanced radiological, chemical and molecular techniques were applied to estimate their probable age, sex and populational affinity. The obtained radiological, isotopic and molecular signatures of the remains were compared with the available databases to estimate their affinity with the individuals of geographic area to whom the remains reportedly belonged to. The maternally inherited mtDNA haplogroup assignments, and stable isotope analysis of carbon and oxygen suggested that the studied human remains belonged to the individuals from West Bengal, Bihar, Odisha, Awadh (presently in Uttar Pradesh) and parts of Meghalaya and Manipur as potential regions of their geographic identity and thus, attributing the victims to be non-local to the site. However, merely on the basis of forensic anthropological examinations of very few bones and teeth (collected out of a huge collection of thousands of bones and teeth); it would be just an unqualified and sweeping conclusion to claim their identity as adult or non-adult, male or female, local or non-local, victims of 1857 mass killings or to the victims of ceremonial sacrifices or criminal activities committed in the past. A sufficient number of bones and teeth along with items of personal identity needs to be examined with multiple scientific techniques to arrive at some valid conclusions about their biological identity.

Exploratory analysis of mtDNA haplogroups in two Alzheimer's longitudinal cohorts.

Inherited mitochondrial DNA (mtDNA) variants may influence Alzheimer's disease (AD) risk. We sequenced mtDNA from 146 AD and 265 cognitively normal (CN) subjects from the University of Kansas AD Center (KUADC) and assigned haplogroups. We further considered 244 AD and 242 CN AD Neuroimaging Initiative (ADNI) subjects with equivalent data. Without applying multiple comparisons corrections, KUADC haplogroup J AD and CN frequencies were 16.4% versus 7.6% (P = .007), and haplogroup K AD and CN frequencies were 4.8% versus 10.2% (P = .063). ADNI haplogroup J AD and CN frequencies were 10.7% versus 7.0% (P = .20), and haplogroup K frequencies were 4.9% versus 8.7% (P = .11). For the combined 390 AD and 507 CN cases haplogroup J frequencies were 12.8% versus 7.3% (P = .006), odds ratio (OR) = 1.87, and haplogroup K frequencies were 4.9% versus 9.5% (P = .010), OR = 0.49. Associations remained significant after adjusting for apolipoprotein E, age, and sex. This exploratory analysis suggests inherited mtDNA variants influence AD risk.

Damage in Mitochondrial DNA Associated with Parkinson's Disease.

Mitochondria are the only organelles that contain their own genetic material (mtDNA). Mitochondria are involved in several key physiological functions, including ATP production, Ca2+ homeostasis, and metabolism of neurotransmitters. Since these organelles perform crucial processes to maintain neuronal homeostasis, mitochondrial dysfunctions can lead to various neurodegenerative diseases. Several mitochondrial proteins involved in ATP production are encoded by mtDNA. Thus, any mtDNA alteration can ultimately lead to mitochondrial dysfunction and cell death. Accumulation of mutations, deletions, and rearrangements in mtDNA has been observed in animal models and patients suffering from Parkinson's disease (PD). Also, specific inherited variations associated with mtDNA genetic groups (known as mtDNA haplogroups) are associated with lower or higher risk of developing PD. Consequently, mtDNA alterations should now be considered important hallmarks of this neurodegenerative disease. This review provides an update about the role of mtDNA alterations in the physiopathology of PD.

Association between Mitochondrial DNA Sequence Variants and V˙O2 max Trainability.

We designed the study to determine whether mitochondrial DNA (mtDNA) haplogroup, sequence, and heteroplasmy differed between individuals previously characterized as low (LR) or high responders (HR) as defined by their maximal oxygen uptake response to a standardized aerobic exercise training program. DNA was isolated from whole blood in subjects from the HERITAGE Family Study that were determined to be either HR (n = 15) or LR (n = 15). mtDNA was amplified by long-range polymerase chain reaction, then tagged with Nextera libraries and sequenced on a MiSeq instrument. Different mtDNA haplogroup subtypes were found in HR and LR individuals. Compared with HR subjects, significantly more LR subjects had variants in 13 sites, including 7 in hypervariable (HV) regions: HV2 (G185A: 0 vs 6, P = 0.02; G228A: 0 vs 5, P = 0.04; C295T: 0 vs 6; P = 0.04), HV3 (C462T: 0 vs 5, P = 0.04; T489C: 0 vs 5; P = 0.04), and HV1 (C16068T: 0 vs 6, P = 0.02; T16125C: 0 vs 6, P = 0.02). Remaining variants were in protein coding genes, mtND1 (1 vs 8, P = 0.02), mtND3 (A10397G: 0 vs 5, P = 0.04), mtND4 (A11250G: 1 vs 8, P = 0.02), mtND5 (G13707A: 0 vs 5, P = 0.04), and mtCYTB (T14797C: 0 vs 5, P = 0.04; C15451A: 1 vs 8, P = 0.02). Average total numbers of heteroplasmies (P = 0.83) and frequency of heteroplasmies (P = 0.05) were similar between the groups. Our findings provide specific sites across the mitochondrial genome that may be related to maximal oxygen uptake trainability.

Association between mitochondrial DNA haplogroup variation and coronary artery disease

Background and aimsMitochondrial DNA (mtDNA) haplogroups have been associated with the development of coronary artery disease (CAD) in European populations. However, the specific mtDNA haplogroups associated with CAD have not been investigated in Chinese populations. Methods and resultsHere, we carried out a case–control study including 1036 and 481 CAD patients and 973 and 511 geographically matched asymptomatic control subjects in southern and northern China, respectively. After adjusting for age and gender, our results indicated that mtDNA haplogroups are not associated with the occurrence of CAD and its subcategories, acute coronary syndromes and stable coronary heart disease, in both southern and northern Chinese populations. By focusing on the southern Chinese population, we further revealed that mtDNA haplogroups are not associated with CAD severity.Type 2 diabetes (T2D) and hypertension are two key driving factors for the development of CAD, nonetheless, we found that the frequencies of the 12 studied mtDNA haplogroups did not differ between patients with and without T2D or hypertension. ConclusionmtDNA haplogroups are not associated with the occurrence of CAD or its subcategories in Chinese populations. Other factors such as environment and nuclear genetic background may contribute to the occurrence of CAD.

Germline and somatic mtDNA mutation spectrum of rheumatoid arthritis patients in the Taizhou area, China.

Reactive oxygen species are believed to be involved in the onset of RA, and the association between nuclear-encoded mitochondrial respiratory chain-related variants and RA has recently been revealed. However, little is known about the landscape of mitochondrial DNA (mtDNA) variants in RA. Next-generation sequencing was conducted to profile mtDNA germline and somatic variants in 124 RA patients and 123 age- and sex-matched healthy controls in the Taizhou area, China. Fisher's exact test, SKAT and SKAT-O were used for gene-burden tests to investigate RA-related variants of mitochondrial genes. Predictive tools were applied to evaluate the pathogenicity of mtDNA variants, and mtDNA haplogroups were assigned according to mtDNA mutations recorded in PhyloTree database. The frequency distribution of mtDNA haplogroups between the groups was compared using χ2 analysis. We identified 467 RA-unique and 341 healthy control-unique mtDNA variants, with 443 common variants. Only MT-ATP6 with a significant burden of variants was identified by Fisher's exact test, SKAT and SKAT-O, even after Bonferroni adjustment, and the enrichment variants in MT-ATP6 was mainly driven by m.8830C>A, m.8833G>C and m.8843T>A variants. Besides, four frequently low-heteroplasmic variants including the three variants above and m.14135T>G of MT-ND5 were detected in RA only; except for m.8830C>A, they are considered potential pathogenicity based on functional predictions. χ2 analysis before Bonferroni adjustment revealed haplogroup F1/F1a to be negatively associated with RA (P<0.05). These results profiled the landscape of germline and somatic mtDNA variants in RA and supported the effects of mitochondrial genes on RA.

MOLECULAR GENETIC MARKERS IN ASSESSING THE RESULTS OF VARIOUS OPTIONS FOR LYMPH DISSECTION IN GASTRIC CANCER. EXPLORATORY RESEARCH

The research analyzes a patient-oriented methodology for assessing the results of various options for lymph dissection in gastric cancer based on the study of molecular genetic markers in the non-recombining part of the Y chromosome and in mitochondrial DNA (haplogroups). Significant heterogeneity was established among patients in world randomized trials who underwent resection operations on the stomach with various options for lymph dissection. In the Y chromosome, the haplogroup with the designation O was predominant in patients of Asian studies (59 % - 95 % of cases) with the designation O. The second most frequent (14 % - 72 % of cases, patients in European studies) was the haplogroup R1b. The total number of patients with mitochondrial macrogaplogroup N (mainly haplogroups H and U) was almost twice as many as patients with macrogaplogroup M (D haplogroup). According to the results of our own exploratory study, in all patients operated on for gastric cancer, haplogroup R1a was verified in the Y chromosome. Clusters of macrogaplogroup N (U, H, T) predominated in mitochondrial DNA. Thus, one of the approaches ensuring the homogeneity of comparison groups in assessing various options for lymph dissection in gastric cancer is to assess their comparability based on haploid molecular genetic markers.

Mitochondrial DNA Haplogroups and Susceptibility to Neuroblastoma.

Neuroblastoma is a childhood malignancy that arises from the developing sympathetic nervous system. Although mitochondrial dysfunctions have been implicated in the pathophysiology of neuroblastoma, the role of mitochondrial DNA (mtDNA) has not been extensively investigated. A total of 2404 Caucasian children diagnosed with neuroblastoma and 9310 ancestry-matched controls were recruited at the Children's Hospital of Philadelphia. The mtDNA haplogroups were identified from SNP array data of two independent cohorts. We conducted a case-control study to explore potential associations of mtDNA haplogroups with the susceptibility of neuroblastoma. The genetic effect of neuroblastoma was measured by odds ratios (ORs) of mitochondrial haplogroups. All tests were two-sided. Haplogroup K was statistically significantly associated with reduced risk of neuroblastoma in the discovery cohort consisting of 1474 cases and 5699 controls (OR = 0.72, 95% confidence interval [CI] = 0.57 to 0.90; P = 4.8 × 10-3). The association was replicated in an independent cohort (OR = 0.69, 95% CI = 0.53 to 0.92; P = .01) of 930 cases and 3611 controls. Pooled analysis was performed bycombining the two data sets. The association remained highly statistically significant after correction for multiple testing (OR = 0.71, 95% CI = 0.59 to 0.84, P = 1.96 × 10-4, Pcorrected = .002). Further analysis focusing on neuroblastoma subtypes indicated haplogroup K was more associated with high-risk neuroblastoma (OR = 0.57, 95% CI = 0.43 to 0.76; P = 1.46 × 10-4) than low-risk and intermediate-risk neuroblastoma. Haplogroup K is an independent genetic factor associated with reduced risk of developing neuroblastoma in European descents. These findings provide new insights into the genetic basis of neuroblastoma, implicating mitochondrial DNA encoded proteins in the etiology of neuroblastoma.

Analysis of maternal lineage structure of individuals from chamber graves placed in medieval cemetery in Kałdus, Central Poland.

The beginning of the early Middle Ages period in Poland (10th-14th century) has been widely debated in the context of an active demographic inflow from other countries and its contribution to the creation of the new country. Finding chamber graves which are considered typical for the Scandinavian ethnic group in a few cemeteries in Poland has become the basis for the anthropological inference on the potential participation of North European people in forming the social elite of medieval Poland. However, the question of whether this fact was the result of presence of people from other countries lacks an unambiguous answer. We attempted to isolate ancient DNA from the medieval necropolis in Kałdus where several chamber graves have been found and analysed the genetic diversity of maternal lineage of this population. We analysed the HVR I fragment and coding regions to assess the mitochondrial DNA haplogroup. We have identified a few relatively rare haplogroups (A2, T2b4a, HV, K1a11, J2b1a, and X2) which were previously found in early medieval sites in Norway and Denmark. Obtained results might suggest genetic relation between the people of Kałdus and past northern Europe populations. Present and further research can undoubtedly shed new light on the aspect of the formation of the early medieval Polish population.

Validation of a 52-mtSNP minisequencing panel for haplogroup classification of forensic DNA samples.

Mitochondrial DNA (mtDNA) is a useful tool in forensic investigation as it provides information about the matrilineal ancestry of individuals. In addition, mtDNA can be analyzed when the analysis of other nuclear markers is underperforming. Recently, we developed a minisequencing panel for the simultaneous analysis of 52 mtDNA SNPs to classify maternal lineages into the main haplogroups and their phylogeographic origin. In order to make this panel suitable for forensic genetics laboratories, a validation study has been performed in accordance with the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines, including species specificity, reproducibility, sensitivity, and stability tests. The results demonstrate that the panel of 52 mtDNA SNPs is highly sensitive, since it enables to obtain complete genetic profiles of samples containing minimal amounts of DNA (1pg). Furthermore, it provides sufficient genetic information to detect the matrilineal biogeographical origin of highly degraded samples, i.e., ancient dating skeletal remains, and samples with the presence of inhibitors, such as hematin and humic acid. In addition, this panel can detect mixtures in samples whose mtDNA haplogroups of contributors are different. Overall, the results of this study demonstrate the suitability of this minisequencing panel of 52 mtDNA SNPs to be used in forensic cases, with samples of low amount or degraded DNA.