Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans

PurposeReports have questioned the dogma of exclusive maternal transmission of human mitochondrial DNA (mtDNA), including the recent report of an admixture of two mtDNA haplogroups in individuals from three multigeneration families. This was interpreted as being consistent with biparental transmission of mtDNA in an autosomal dominant–like mode. The authenticity and frequency of these findings are debated.MethodsWe retrospectively analyzed individuals with two mtDNA haplogroups from 2017 to 2019 and selected four families for further study.ResultsWe identified this phenomenon in 104/27,388 (approximately 1/263) unrelated individuals. Further study revealed (1) a male with two mitochondrial haplogroups transmits only one haplogroup to some of his offspring, consistent with nuclear transmission; (2) the heteroplasmy level of paternally transmitted variants is highest in blood, lower in buccal, and absent in muscle or urine of the same individual, indicating it is inversely correlated with mtDNA content; and (3) paternally transmitted apparent large-scale mtDNA deletions/duplications are not associated with a disease phenotype.ConclusionThese findings strongly suggest that the observed mitochondrial haplogroup of paternal origin resulted from coamplification of rare, concatenated nuclear mtDNA segments with genuine mtDNA during testing. Evaluation of additional specimen types can help clarify the clinical significance of the observed results.     

Comparative analysis of the complete mitochondrial genome between Tibetan and Han population

OBJECTIVE: To construct the haplogroup and perform an analysis of mitochondrial whole-genome sequence in Tibetan and Han Chinese. Variations of nucleotide of mitochondrial DNA (mtDNA) were identified and compared between the Tibetan and Han population. METHODS: The mtDNA whole sequences of 40 Tibetan and 50 Han individuals were sequenced by an Applied Biosystems 3730 DNA automatic sequencer. The sequences were assembled using software phredPhrap16.0, and all assembled sequences were manually verified according to the criterion of rCRS (revised Cambridge Reference Sequence). The haplogroups of mtDNA were constructed using phylogenetic analysis according to the criteria of MITOMAP by Network method. The data were elucidated by integrated methods. RESULTS: Authors' results showed that all the pooled 90 subjects belonged to the Macrohaplogroup M and N, and were classified into 13 haplogroups. No differences were observed among the haplogroups of the two populations except for M9 haplogroup. A total of 21 variants were detected by comparing the mtDNA whole sequences between Tibetan and Han population; of those, 5 variants have not been reported before. In addition, we constructed the haplotypes of 5 variants harboring the D-loop region, and founded prominent difference in both supertype 1 and supertype 2 between Tibetan and Han population. CONCLUSION: The phylogenetic analysis indicates that the Tibetan and Han ethnic groups shared close maternal relationship in origin. The biological implication of the significant variants is worth elucidating; whether they are the results of adaptive selection or neutral selection or pathological variations need to be further studied.     

Review of Croatian genetic heritage as revealed by mitochondrial DNA and Y chromosomal lineages

The aim of this review is to summarize the existing data collected in high-resolution phylogenetic studies of mitochondrial DNA and Y chromosome variation in mainland and insular Croatian populations. Mitochondrial DNA polymorphisms were explored in 721 individuals by sequencing mtDNA HVS-1 region and screening a selection of 24 restriction fragment length polymorphisms (RFLPs), diagnostic for main Eurasian mtDNA haplogroups. Whereas Y chromosome variation was analyzed in 451 men by using 19 single nucleotide polymorphism (SNP)/indel and 8 short tandem repeat (STR) loci. The phylogeography of mtDNA and Y chromosome variants of Croatians can be adequately explained within typical European maternal and paternal genetic landscape, with the exception of mtDNA haplogroup F and Y-chromosomal haplogroup P* which indicate a connection to Asian populations. Similar to other European and Near Eastern populations, the most frequent mtDNA haplogroups in Croatians were H (41.1%), U5 (10.3%), and J (9.7%). The most frequent Y chromosomal haplogroups in Croatians, I-P37 (41.7%) and R1a-SRY1532 (25%), as well as the observed structuring of Y chromosomal variance reveal a clearly evident Slavic component in the paternal gene pool of contemporary Croatian men. Even though each population and groups of populations are well characterized by maternal and paternal haplogroup distribution, it is important to keep in mind that linking phylogeography of various haplogroups with known historic and prehistoric scenarios should be cautiously performed.     

Multiple founder haplotypes of mitochondrial DNA in Amerindians revealed by RFLP and sequencing

The mitochondrial DNA (mtDNA) of 139 individuals from eight tribes which belong to four linguistic groups of the Brazilian Amazon Region was studied both by RFLP and by sequencing of the D-loop region. RFLP analysis showed that 41 haplotypes (29%) belonged to haplogroup A, 39 (28%) to haplogroup B, 38 (27%) to haplogroup C., 19 (14%) to haplogroup D, and 2 (<2%) could not be assigned to any of the four haplogroups. Among the 92 individuals analyzed by direct sequencing of the D-loop region, we observed 43 different haplotypes defined by 48 polymorphic points, while one haplotype could not be assigned to any of the clusters previously described. Joint analysis of data obtained by RFLP and by sequencing of mtDNA demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of contemporary Amerindians cluster into four groups, similar to those previously described, even though 7% of the total sample or 12% of the haplotypes have discrepancies between results obtained by RFLP and sequencing. In addition to supporting the prevalence of four major haplogroups among contemporary Amerindians, our data are compatible with multiple founder haplotypes in each haplogroup, based on: i) a high prevalence of unusual haplotypes; ii) presence of multiple polymorphic sites shared by different haplogroups; iii) relative differences in nucleotide diversity based on RFLP or sequencing within the different haplogroups.     

Maternal genetic link of a south Dravidian tribe with native Iranians indicating bidirectional migration

Abstract

Background: The phylogeny of major mitochondrial DNA haplogroups has played a key role in assessing the people of India through molecular genetics.

Aim: To resolve the phylogeny and phylogeographic pattern of autochthonous haplogroup R with its descendant haplogroup U in the Urali Kuruman tribal population of Southern India.

Subjects and methods: Complete mitogenome sequences of 40 individuals were amplified and sequenced using the Sanger sequencing method. Mutations were scored referring to the revised Cambridge reference sequence, and phylogenetic trees were constructed using previously described sequences.

Results: Novel sub-lineages of haplogroup R30: R30a1c1, and U1: U1a1c1d2, U1a1c1d2a were identified. Urali Kurumans pooled ancestry with the native Iranians sharing the sub-haplogroups R30a1c and U1a1c1d. The coalescence ages estimated for the sub-haplogroup R30a1c dates ～ 9.4?±?3.5 Kya and for subclade U1a1c1d dates ～ 9.1?±?2.7 Kya.

Conclusion: The study revealed a genetic link between Iran and South Asia in the Neolithic time, indicating bidirectional migration and admixture.     

藏汉民族线粒体基因组全序列的比较研究

目的 以藏汉民族线粒体基因组全序列为基础,进行Haplogroup构建和系统发生分析,在全序列水平上比较核苷酸的变异,阐释可能的变异机制和蕴含的生物学意义.方法 采用Applied Biosystems 3730DNA自动测序仪分别对40名藏族和50名汉族的标本进行线粒体DNA序列测定,应用phredPhrap 16.0软件进行全序列拼接,并以rCRS(revised Cambridge Reference Sequence)为标准与测定序列进行比对分析;根据MTTO-MAP的标准,通过Network方法进行Haplogroup构建和系统发生的分析,并结合其它方法对产生的数据进行深入解读.结果 数据分析结果显示:在系统发生上,藏汉民族90个线粒体DNA序列归类到13个Haplogroups,除M9以外,其它各Haplogroup出现频率之间比较差异无统计学意义;通过两个民族的线粒体DNA全序列比对,发现21个分布频率有统计学意义的变异位点,其中的5个为新变异位点;另外,对D-Loop区的5个突变位点进行了单倍型构建,90个标本可分为2种Supertype,发现在藏汉民族之间Supertypel和Supertype 2的分布频率均有统计学意义.结论 藏汉民族在种族起源和系统发生上具有较近的母系遗传关系;在全序列有统计学意义的位点究竟是适应性或者中性选择,抑或是一种病理性突变尚需深入的探讨.     

Mitochondrial haplogroup H correlates with ATP levels and age at onset in Huntington disease

Mitochondrial dysfunction has been implicated in the pathogenesis of Huntington disease (HD), a primarily neurodegenerative disorder that results from an expansion in the polymorphic trinucleotide CAG tract in the HD gene. In order to evaluate whether mitochondrial DNA (mtDNA) variation contributes to HD phenotype we genotyped 13 single nucleotide polymorphisms (SNPs) that define the major European mtDNA haplogroups in 404 HD patients. Genotype-dependent functional effects on intracellular ATP concentrations were assessed in peripheral leukocytes. In patients carrying the most common haplogroup H (48.3%), we demonstrate a significantly lower age at onset (AO). In combination with PGC-1alpha genotypes, 3.8% additional residual variance in HD AO can be explained. Intracellular ATP concentrations in HD patients carrying the cytochrome c oxidase subunit I (CO1) 7028C allele defining haplogroup H were significantly higher in comparison to non-H individuals (mean?±?SEM, 599?±?51.8 ng/ml, n?= 14 vs. 457.5?±?40.4 ng/ml, p?=?0.03, n?=?9). In contrast, ATP concentrations in cells of HD patients independent from mtDNA haplogroup showed no significant differences in comparison to matched healthy controls. Our data suggest that an evolutionarily advantageous mitochondrial haplogroup is associated with functional mitochondrial alterations and may modify disease phenotype in the context of neurodegenerative conditions such as HD.     

Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background

Mitochondrial complex I deficiency has been implicated in the pathogenesis of Parkinson’s disease (PD), but as yet no mitochondrial DNA (mtDNA) variations have been identified that could account for the impaired complex I activity. On the other hand, it has been suggested that mtDNA polymorphisms (mtSNPs) or haplogroups may modify the risk of developing PD. Here, we determined the distributions of ten mtSNPs that define the nine major European haplogroups among 224 PD patients and 383 controls from Crete, an island of 0.6 million inhabitants who share a similar genetic background and a common environment. The recruitment of patients and controls was restricted to individuals of Cretan origin for at least three generations from both parental sides in order to avoid population admixture and subsequent genetic heterogeneity. We found no mtSNP or mtDNA haplogroup that predisposes to PD, although there was a trend for haplogroups J, T, U and I and the supercluster of haplogroups UKJT to be slightly underrepresented in our PD patients as compared to controls. While a combination of common mtSNPs (present in ≥5% of the general population) may decrease the chance of developing PD, this effect was minor in the Cretan population.     

Association between mitochondrial DNA haplogroup and myelodysplastic syndromes

Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non‐Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS‐R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population‐based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc.     

Analysis of European mitochondrial haplogroups with Alzheimer disease risk

We examined the association of mtDNA variation with Alzheimer disease (AD) risk in Caucasians (989 cases and 328 controls) testing the effect of individual haplogroups and single nucleotide polymorphisms (SNPs). Logistic regression analyses were used to assess risk of haplogroups and SNPs with AD in both main effects and interaction models. Males classified as haplogroup U showed an increase in risk (OR = 2.30; 95% CI, 1.03-5.11; P = 0.04) of AD relative to the most common haplogroup H, while females demonstrated a significant decrease in risk with haplogroup U (OR = 0.44 ; 95% CI, 0.24-0.80; P = 0.007). Our results were independent of APOE genotype, demonstrating that the effect of mt variation is not confounded by APOE4 carrier status. We suggest that variations within haplogroup U may be involved in AD expression in combination with environmental exposures or nuclear proteins other than APOE.     

Mitochondrial DNA variation in Jordanians and their genetic relationship to other Middle East populations

Background: The Levant is a crucial region in understanding human migrations between Africa and Eurasia. Although some mitochondrial DNA (mtDNA) studies have been carried out in this region, they have not included the Jordan area. This paper deals with the mtDNA composition of two Jordan populations.

Aim: The main objectives of this article are: first, to report mtDNA sequences of an urban and an isolate sample from Jordan and, second, to compare them with each other and with other nearby populations.

Subjects and methods: The analyses are based on HVSI and HVSII mtDNA sequences and diagnostic RFLPs to unequivocally classify into haplogroups 101 Amman and 44 Dead Sea unrelated individuals from Jordan.

Results: Statistical analysis revealed that, whereas the sample from Amman did not significantly differ from their Levantine neighbours, the Dead Sea sample clearly behaved as a genetic outlier in the region. Its outstanding Eurasian haplogroup U3 frequency (39%) and its south-Saharan Africa lineages (19%) are the highest in the Middle East. On the contrary, the lack ((preHV)1) or comparatively low frequency (J and T) of Neolithic lineages is also striking. Although strong drift by geographic isolation could explain the anomalous mtDNA pool of the Dead Sea sample, the fact that its mtDNA lineage composition mirrors, in geographic origin and haplogroup frequencies, its Y-chromosome pool, points to founder effect as the main cause. Ancestral M1 lineages detected in Jordan that have affinities with those recently found in Northwest but not East Africa question the African origin of the M1 haplogroup.

Conclusion: Results are in agreement with an old human settlement in the Jordan region. However, in spite of the attested migratory spreads, genetically divergent populations, such as that of the Dead Sea, still exist in the area.     

Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson's disease in Italians

It has been proposed that European mitochondrial DNA (mtDNA) haplogroups J and K, and their shared 10398G single-nucleotide polymorphism (SNP) in the ND3 gene, are protective from Parkinson's disease (PD). We evaluated the distribution of the different mtDNA haplogroups in a large cohort of 620 Italian patients with adult-onset (>50, <65 years of age) idiopathic PD vs two groups of ethnic-matched controls. Neither the frequencies of haplogroup J nor that of 10398G were significantly different. However, the frequency of haplogroup K was significantly lower in PD. Stratification by sex and age indicated that the difference in the distribution of haplogroup K was more prominent in >50 year old males. In spite of the common 10398G SNP, haplogroups J and K belong to widely diverging mitochondrial clades, a consideration that may explain the different results obtained for the two haplogroups in our cohorts. Our study suggests that haplogroup K might confer a lower risk for PD in Italians, corroborating the idea that the mitochondrial oxidative phosphorylation pathway is involved in the susceptibility to idiopathic PD.     

Analysis of Y-chromosome Variability and its Comparison with mtDNA Variability Reveals Different Demographic Histories Between Islands in the Azores Archipelago (Portugal)

We determined the Y‐chromosomal composition of the population of the Azores Islands (Portugal), by analyzing 20 binary polymorphisms located in the non‐recombining portion of the Y‐chromosome (NRY), in 185 unrelated individuals from the three groups of islands forming the Archipelago (Eastern, Central and Western). Similar to that described for other Portuguese samples, the most frequent haplogroups were R1(xR1b3f) (55.1%), E(xE3a) (13%) and J (8.6%). Principal components analysis revealed a Western European profile for the Azorean population. No significant differences between Azores and mainland Portugal were observed. However, the haplogroup distribution across the three groups of islands was not similar (P<0.003). The Western group presented differences in the frequencies of haplogroups R1, E(xE3a) and I1b2 (27.3%, 22.7% and 13.6%, respectively) when compared to the other two groups. An assessment of the NRY variability, and its comparison with mitochondrial DNA (mtDNA) variability, was further evidence of the differential composition of males during the settlement of the three groups of islands, contrary to what has been previously deduced for the female settlers using mtDNA data.     

High-throughput sequencing of complete human mtDNA genomes from the Philippines

Because of the time and cost associated with Sanger sequencing of complete human mtDNA genomes, practically all evolutionary studies have screened samples first to define haplogroups and then either selected a few samples from each haplogroup, or many samples from a particular haplogroup of interest, for complete mtDNA genome sequencing. Such biased sampling precludes many analyses of interest. Here, we used high-throughput sequencing platforms to generate, rapidly and inexpensively, 109 complete mtDNA genome sequences from random samples of individuals from three Filipino groups, including one Negrito group, the Mamanwa. We obtained on average ～55-fold coverage per sequence, with <1% missing data per sequence. Various analyses attest to the accuracy of the sequences, including comparison to sequences of the first hypervariable segment of the control region generated by Sanger sequencing; patterns of nucleotide substitution and the distribution of polymorphic sites across the genome; and the observed haplogroups. Bayesian skyline plots of population size change through time indicate similar patterns for all three Filipino groups, but sharply contrast with such plots previously constructed from biased sampling of complete mtDNA genomes, as well as with an artificially constructed sample of sequences that mimics the biased sampling. Our results clearly demonstrate that the high-throughput sequencing platforms are the methodology of choice for generating complete mtDNA genome sequences.     

Mitochondrial DNA haplogroups do not influence the Huntington's disease phenotype

Various lines of evidence demonstrate the involvement of mitochondrial dysfunction in the pathogenesis of Huntington's disease (HD). However, the precise role of mitochondria in the neurodegenerative cascade leading to HD is still unclear. Mitochondrial DNA (mtDNA) haplogroups-specific polymorphisms were previously related to several neurodegenerative diseases. The length of CAG repeat seems to be related to the clinical features of HD, such as age of onset and progression of motor impairment. The basis for the impaired cognitive functions and for the mood changes is less clear. Aim of this study was to determine whether mtDNA polymorphism(s) play the role of "modifier gene(s)" in this disease. In this work we have genotyped predefined European mtDNA haplogroups in 51 patients with HD and 181 matched controls. The frequency of the haplogroups and haplogroup clusters did not differ between the two groups, and no correlation with gender, age of onset and disease status was observed. No significant difference was observed between different haplogroups and haplogroup clusters in the cognitive or motor progression of the disease. Our study does not support any association between mtDNA haplogroups and HD.     

Development of a multiplex single base extension assay for mitochondrial DNA haplogroup typing

Aim

To provide a screening tool to reduce time and sample consumption when attempting mtDNA haplogroup typing.

Methods

A single base primer extension assay was developed to enable typing, in a single reaction, of twelve mtDNA haplogroup specific polymorphisms. For validation purposes a total of 147 samples were tested including 73 samples successfully haplogroup typed using mtDNA control region (CR) sequence data, 21 samples inconclusively haplogroup typed by CR data, 20 samples previously haplogroup typed using restriction fragment length polymorphism (RFLP) analysis, and 31 samples of known ancestral origin without previous haplogroup typing. Additionally, two highly degraded human bones embalmed and buried in the early 1950s were analyzed using the single nucleotide polymorphisms (SNP) multiplex.

Results

When the SNP multiplex was used to type the 96 previously CR sequenced specimens, an increase in haplogroup or macrohaplogroup assignment relative to conventional CR sequence analysis was observed. The single base extension assay was also successfully used to assign a haplogroup to decades-old, embalmed skeletal remains dating to World War II.

Conclusion

The SNP multiplex was successfully used to obtain haplogroup status of highly degraded human bones, and demonstrated the ability to eliminate possible contributors. The SNP multiplex provides a low-cost, high throughput method for typing of mtDNA haplogroups A, B, C, D, E, F, G, H, L1/L2, L3, M, and N that could be useful for screening purposes for human identification efforts and anthropological studies.Mitochondrial DNA (mtDNA) is a 16 569 bp circular molecule present, on average, in 500 copies per cell (1). MtDNA analysis is utilized in several areas of science including, but not limited to, anthropology, evolutionary studies, and forensic science (2-5). The high copy number, and possibly the cellular location and molecular features of mtDNA, allow for increased recovery, thus providing a distinct advantage over nuclear DNA when working with highly compromised samples (6). The maternal inheritance and high mutation rate are characteristics extremely useful for evolutionary studies (7,8); in fact, mtDNA has been used to resolve evolutionary questions related to extinct species and to human migrations throughout the continents (9-12). The field of forensic science also relies upon mtDNA to identify missing persons, locate maternal relatives, identify victims in mass disasters, and, in some situations, include an individual at a crime scene (13-19).Early studies of the mtDNA genome revealed patterns of variation that were linked to geographic regions. Individuals with the same sequence variations were clustered into haplogroups defined by mutations at particular nucleotide positions (20-27). A closer examination of the mtDNA genomes of various populations led to the following assumptions: 1) several of the mtDNA mutations are highly correlated with the ethnic and geographic origin of the individual, 2) all mutations originated from a single mtDNA tree, and 3) the greatest variation and deepest root of the mtDNA tree is present in the African population. Furthermore, a calculation of the variation between mtDNA haplogroups demonstrated that 35% of the mutations were continent-specific, and therefore useful indicators of geographic origin (24,25,28-31).Before the advent of modern sequencing methods, the primary approach to identifying polymorphic sites throughout the mtDNA coding region was restriction fragment length polymorphism (RFLP) analysis. While this methodology is still utilized in certain contexts, direct sequencing of the mtDNA molecule is rapidly gaining acceptance as the method of choice for haplogroup typing (20,23,30,32-35). Single base primer extension, also known as minisequencing, is an example of a direct sequencing technique that is currently utilized for mtDNA haplogroup typing (36-42). This methodology, described in detail by Fiorentino et al (43), offers several advantages to the investigator over RFLP and conventional sequence analysis methods including the use of small amplicons (<150 bp), increased sensitivity and robustness, and multiplexing capability. Multiplexing capability is particularly important, especially in regard to forensic DNA analysis, as it reduces sample consumption while increasing throughput of sample processing and data analysis. Increased sensitivity allows for improved amplification success with DNA samples that contain limited starting template. Additionally, the possibility for high throughput processing can aid in population screening studies in situations where numerous samples need to be typed (44). This is particularly true in mass disaster or other mass screening situations, where a simple and rapid population screening tool that consumes little extract could effectively direct subsequent identification testing. In these situations, coding region sequencing would be expensive and time-consuming, and the subsequent data analysis a lengthy, burdensome, and potentially error-prone process (42,45-48). Furthermore, the possibility of obtaining interpretable results from poor quality polymerase chain reaction (PCR) products while simultaneously typing several polymorphisms throughout the mtDNA genome make it a more feasible method than conventional PCR fragment sequence analysis, especially in forensic cases and anthropological studies involving highly degraded or otherwise compromised human remains (16,36-38,49,50).In this article, we describe the development of a multiplex assay designed to simultaneously type twelve polymorphic positions located throughout the coding region of the mtDNA genome for the identification of haplogroups A, B, C, D, E, F, G, H, I, L1/L2, L3, M, N, and X. The intended utility of this assay is haplogroup typing of highly degraded human remains for either forensic casework or as a low cost, high throughput alternative for screening anthropological specimens. Validation of this assay included the analysis of 20 samples previously haplogroup typed by RFLP, and 94 samples for which haplogroup had been inferred based on control region (CR) sequence data. Additionally, and to evaluate the potential application of the assay for population screening, 31 samples were tested for which only the population of origin, and not the mtDNA haplogroup, was known. Finally, to verify robustness and sensitivity of the assay, we also tested two highly degraded human bones embalmed and buried in the early 1950s.     

Mitochondrial DNA and craniofacial covariability of Chad Basin females indicate past population events

The Chad Basin lies in the middle of the Sudanic African belt between the Sahara and the tropical rain forests. Its present‐day settlement is a result of Holocene climatic changes and human immigrations from different parts of Africa. This study presents a statistical analysis of the relationships of physical features (stature and five main craniofacial measurements) and mitochondrial (mtDNA) haplogroup classifications in a sample of 282 adult individuals belonging to seven populations of different ethno‐linguistic groups living in the Chad Basin. Drawing on the analysis of variance, we identified a female‐specific DNA association between mtDNA haplogroup assignment and facial height. More specifically, the mtDNA haplogroups of East‐African origin occur more frequently in females with relatively longer faces and, conversely, the mtDNA of West‐African origin are found more frequently in females with lower faces. Interestingly, this kind of association is not found in the males of the same populations. Our interpretation refers mainly to population history; we suggest that facial height and mtDNA haplogroup co‐variance in Chad Basin females reflects a long‐term east–west population distribution in the past that made the facial differentiation possible. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

The 12S rRNA A1555G mutation in the mitochondrial haplogroup D5a is responsible for maternally inherited hypertension and hearing loss in two Chinese pedigrees

We reported here clinical, genetic evaluations and molecular analysis of mitochondrial DNA (mtDNA) in two Han Chinese families carrying the known mitochondrial 12S rRNA A1555G mutation. In contrast with the previous data that hearing loss as a sole phenotype was present in the maternal lineage of other families carrying the A1555G mutation, matrilineal relatives among these two Chinese families exhibited both hearing loss and hypertension. Of 21 matrilineal relatives, 9 subjects exhibited both hearing loss and hypertension, 2 individuals suffered from only hypertension and 1 member had only hearing loss. The average age at onset of hypertension in the affected matrilineal relatives of these families was 60 and 46 years, respectively, whereas those of hearing loss in these two families were 33 and 55 years, respectively. Molecular analysis of their mtDNA identified distinct sets of variants belonging to the Eastern Asian haplogroup D5a. In contrast, the A1555G mutation occurred among other mtDNA haplogroups D, B, R, F, G, Y, M and N, respectively. Our data further support that the A1555G mutation is necessary but by itself insufficient to produce the clinical phenotype. The other modifiers are responsible for the phenotypic variability of matrilineal relatives within and among these families carrying the A1555G mutation. Our investigation provides the first evidence that the 12S rRNA A1555G mutation leads to both of hearing loss and hypertension. Thus, our findings may provide the new insights into the understanding of pathophysiology and valuable information for management and treatment of maternally inherited hearing loss and hypertension.     

Autosomal Microsatellite and mtDNA Genetic Analysis in Sicily (Italy)

DNA samples from 465 blood donors living in 7 towns of Sicily, the largest island of Italy, have been collected according to well defined criteria, and their genetic heterogeneity tested on the basis of 9 autosomal microsatellite and mitochondrial DNA polymorphisms for a total of 85 microsatellite allele and 10 mtDNA haplogroup frequencies. A preliminary account of the results shows that: a) the samples are genetically heterogeneous; b) the first principal coordinates of the samples are correlated more with their longitude than with their latitude, and this result is even more remarkable when one outlier sample (Butera) is not considered; c) distances among samples calculated from allele and haplogroup frequencies and from the isonymy matrix are weakly correlated (r = 0.43, P = 0.06) but such correlation disappears (r = 0.16) if the mtDNA haplogroups alone are taken into account; d) mtDNA haplogroups and microsatellite distances suggest settlements of people occurred at different times: divergence times inferred from microsatellite data seem to describe a genetic composition of the town of Sciacca mainly derived from settlements after the Roman conquest of Sicily (First Punic war, 246 BC), while all other divergence times take root from the second to the first millennium BC, and therefore seem to backdate to the pre‐Hellenistic period. A more reliable association of these diachronic genetic strata to different historical populations (e.g. Sicani, Elymi, Siculi), if possible, must be postponed to the analysis of more samples and hopefully more informative uniparental DNA markers such as the recently available DHPLC‐SNP polymorphisms of the Y chromosome.     

Different contributions of ancient mitochondrial and Y-chromosomal lineages in 'Karretjie people' of the Great Karoo in South Africa

The Karretjie people of the South African Great Karoo are itinerants who subsist by sheep shearing. Although officially classified 'Coloured', they are aware of their Khoe and San roots. To investigate the maternal and paternal ancestries of the Karretjie people we analyzed their mitochondrial and Y-chromosome DNA variation. Their genetic ancestry was compared with a neighboring group of 'Coloured' individuals. We found that the mitochondrial DNA (mtDNA) haplogroup L0d was present in all the Karretjie people examined, suggesting a maternal contribution, exclusively from the Khoe and San, whereas the paternal ancestry in males was more heterogeneous. The Coloured sample, on the other hand, were found to have a lower frequency of L0d (64.5%), but did harbor other African (27.6%) and non-African (7.9%) mtDNA haplogroups. Similar to the Karretjie people, the Y-chromosome lineages identified in the Coloured group had heterogeneous origins. This study also enabled an assessment of mtDNA variation within L0d sub-haplogroups. All seven of the L0d sub-clades were identified in the combined sample and were used to construct an L0d network.