Biomedical subjects

Qing-Peng Kong

Publications and source records attributed to Qing-Peng Kong.

16 recordsLinked to original sources

PubMed2006

The role of climate in human mitochondrial DNA evolution: a reappraisal.

Previous studies have proposed that selection has been involved in the differentiation of human mitochondrial DNA (mtDNA) and climate was the main driving force. This viewpoint, however, gets no support from the subsequent studies and remains controversial thus far. To clarify this issue, a total of 237 complete mtDNA sequences belonging to autochthonous lineages from South Asia, Oceania, and East Asia were collected to seek for the imprint of selection. Based on nonsynonymous (N) and synonymous (S) substitutions analysis, our results confirmed that purifying selection was the predominant force during the evolution of human mtDNA. However, no significant and extensive difference was detected among these three regions, which did not support the climate adaptation hypothesis but preferred random genetic drift to be the main factor in shaping the current landscape of human mtDNA, at least those from Asian and Oceanian regions.

Amino Acid Substitution↗

PubMed2006

mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese.

Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL.

Aminoglycosides↗

PubMed2006

Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations.

Knowledge about the world phylogeny of human mitochondrial DNA (mtDNA) is essential not only for evaluating the pathogenic role of specific mtDNA mutations but also for performing reliable association studies between mtDNA haplogroups and complex disorders. In the past few years, the main features of the East Asian portion of the mtDNA phylogeny have been determined on the basis of complete sequencing efforts, but representatives of several basal lineages were still lacking. Moreover, some recently published complete mtDNA sequences did apparently not fit into the known phylogenetic tree and conflicted with the established nomenclature. To refine the East Asian mtDNA tree and resolve data conflicts, we first completely sequenced 20 carefully selected mtDNAs--likely representatives of novel sub-haplogroups--and then, in order to distinguish diagnostic mutations of novel haplogroups from private variants, we applied a 'motif-search' procedure to a large sample collection. The novel information was incorporated into an updated East Asian mtDNA tree encompassing more than 1000 (near-) complete mtDNA sequences. A reassessment of the mtDNA data from a series of disease studies testified to the usefulness of such a refined mtDNA tree in evaluating the pathogenicity of mtDNA mutations. In particular, the claimed pathogenic role of mutations G3316A, T3394C, A4833G and G15497A appears to be most questionable as those initial claims were derived from anecdotal findings rather than e.g. appropriate association studies. Following a guideline based on the phylogenetic knowledge as proposed here could help avoiding similar problems in the future.

Asian People↗

PubMed2006

Comment on "Reconstructing the origin of Andaman islanders".

On the basis of mitochondrial DNA sequence analyses, Thangaraj et al. (Brevia, 13 May 2005, p. 996) proposed that Andaman islanders descended from the first humans to migrate out of Africa. We identified mitochondrial DNA from two northeast Indian Rajbanshi individuals that shares three specific mutations with the M31a lineage observed in the Great Andamanese, which suggests that the predecessor of haplogroup M31 originated on the Indian subcontinent.

Africa↗

PubMed2005

The dazzling array of basal branches in the mtDNA macrohaplogroup M from India as inferred from complete genomes.

Many efforts based on complete mitochondrial DNA (mtDNA) genomes have been made to depict the global mtDNA landscape, but the phylogeny of Indian macrohaplogroup M has not yet been resolved in detail. To fill this lacuna, we took the same strategy as in our recent analysis of Indian mtDNA macrohaplogroup N and selected 56 mtDNAs from over 1,200 samples across India for complete sequencing, with the intention to cover all Indian autochthonous M lineages. As a result, the phylogenetic status of previously identified haplogroups based on control-region and/or partial coding-region information, such as M2, M3, M4, M5, M6, M30, and M33, was solidified or redefined here. Moreover, seven novel basal M haplogroups (viz., M34-M40) were identified, and yet another five singular branches of the M phylogeny were discovered in the present study. The comparison of matrilineal components among India, East Asia, Southeast Asia, and Oceania at the deepest level yielded a star-like and nonoverlapping pattern, reflecting a rapid mode of modern human dispersal along the Asian coast after the initial "out-of-Africa" event.

DNA, Mitochondrial↗

PubMed2005

Low "penetrance" of phylogenetic knowledge in mitochondrial disease studies.

An up-to-date view of the worldwide mitochondrial DNA (mtDNA) phylogeny together with an evaluation of the conservation of each site is a reliable tool for detecting errors in mtDNA studies and assessing the functional importance of alleged pathogenic mutations. However, most of the published studies on mitochondrial diseases make very little use of the phylogenetic knowledge that is currently available. This drawback has two inadvertent consequences: first, there is no sufficient a posteriori quality assessment of complete mtDNA sequencing efforts; and second, no feedback is provided for the general mtDNA database when apparently new mtDNA lineages are discovered. We demonstrate, by way of example, these issues by reanalysing three mtDNA sequencing attempts, two from Europe and another one from East Asia. To further validate our phylogenetic deductions, we completely sequenced two mtDNAs from healthy subjects that nearly match the mtDNAs of two patients, whose sequences gave problematic results.

Artifacts↗

PubMed2005

Phantom mutation hotspots in human mitochondrial DNA.

Phantom mutations are systematic artifacts generated in the course of the sequencing process. Contra common belief these artificial mutations are nearly ubiquitous in sequencing results, albeit at frequencies that may vary dramatically. The amount of artifacts depends not only on the sort of automated sequencer and sequencing chemistry employed, but also on other lab-specific factors. An experimental study executed on four samples under various combinations of sequencing conditions revealed a number of phantom mutations occurring at the same sites of mitochondrial DNA (mtDNA) repeatedly. To confirm these and identify further hotspots for artifacts, > 5000 mtDNA electropherograms were screened for artificial patterns. Further, > 30 000 published hypervariable segment I sequences were compared at potential hotspots for phantom mutations, especially for variation at positions 16085 and 16197. Resequencing of several samples confirmed the artificial nature of these and other polymorphisms in the original publications. Single-strand sequencing, as typically executed in medical and anthropological studies, is thus highly vulnerable to this kind of artifacts. In particular, phantom mutation hotspots could easily lead to misidentification of somatic mutations and to misinterpretations in all kinds of clinical mtDNA studies.

Artifacts↗

PubMed2004

Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia.

To resolve the phylogeny of the autochthonous mitochondrial DNA (mtDNA) haplogroups of India and determine the relationship between the Indian and western Eurasian mtDNA pools more precisely, a diverse subset of 75 macrohaplogroup N lineages was chosen for complete sequencing from a collection of >800 control-region sequences sampled across India. We identified five new autochthonous haplogroups (R7, R8, R30, R31, and N5) and fully characterized the autochthonous haplogroups (R5, R6, N1d, U2a, U2b, and U2c) that were previously described only by first hypervariable segment (HVS-I) sequencing and coding-region restriction-fragment-length polymorphism analysis. Our findings demonstrate that the Indian mtDNA pool, even when restricted to macrohaplogroup N, harbors at least as many deepest-branching lineages as the western Eurasian mtDNA pool. Moreover, the distribution of the earliest branches within haplogroups M, N, and R across Eurasia and Oceania provides additional evidence for a three-founder-mtDNA scenario and a single migration route out of Africa.

Base Sequence↗

PubMed2004

Different matrilineal contributions to genetic structure of ethnic groups in the silk road region in china.

Previous studies have shown that there were extensive genetic admixtures in the Silk Road region. In the present study, we analyzed 252 mtDNAs of five ethnic groups (Uygur, Uzbek, Kazak, Mongolian, and Hui) from Xinjiang Province, China (through which the Silk Road once ran) together with some reported data from the adjacent regions in Central Asia. In a simple way, we classified the mtDNAs into different haplogroups (monophyletic clades in the rooted mtDNA tree) according to the available phylogenetic information and compared their frequencies to show the differences among the matrilineal genetic structures of these populations with different demographic histories. With the exception of eight unassigned M*, N*, and R* mtDNAs, all the mtDNA types identified here belonged to defined subhaplogroups of haplogroups M and N (including R) and consisted of subsets of both the eastern and western Eurasian pools, thus providing direct evidence supporting the suggestion that Central Asia is the location of genetic admixture of the East and the West. Although our samples were from the same geographic location, a decreasing tendency of the western Eurasian-specific haplogroup frequency was observed, with the highest frequency present in Uygur (42.6%) and Uzbek (41.4%) samples, followed by Kazak (30.2%), Mongolian (14.3%), and Hui (6.7%). No western Eurasian type was found in Han Chinese samples from the same place. The frequencies of the eastern Eurasian-specific haplogroups also varied in these samples. Combined with the historical records, ethno-origin, migratory history, and marriage customs might play different roles in shaping the matrilineal genetic structure of different ethnic populations residing in this region.

Base Sequence↗

PubMed2004

Phylogeographic analysis of mitochondrial DNA haplogroup F2 in China reveals T12338C in the initiation codon of the ND5 gene not to be pathogenic.

In this report, we studied on a homoplasmic T12338C change in mitochondrial DNA (mtDNA), which substituted methionine in the translational initiation codon of the NADH dehydrogenase subunit 5 gene ( ND5) with threonine. This nucleotide change was originally identified in two mtDNAs belonging to haplogroup F2 by our previous complete sequencing of 48 mtDNAs. Since then, a total of 76 F2 mtDNAs have been identified by the variations occurring in the hypervariable segments and coding regions among more than 3,000 individuals across China. As the T12338C change was detected in 32 samples representing various sub-clades of the F2 haplogroup while not in 14 non-F2 controls, we believe that the T12338C change is specific to the F2 haplogroup. As F2 and its sub-clades were widely distributed in normal individuals of various Chinese populations, we conclude that T12338C is not pathogenic. In addition, based on the average distribution frequency, haplotype diversity and nucleotide diversity of haplogroup F2 in the populations across China, the T12338C nucleotide substitution seems to have been occurred in north China about 42,000 years ago. Our results provided a good paradigm for distinguishing a polymorphic change from a pathogenic mutation based on mtDNA phylogeny.

Amino Acid Substitution↗

PubMed2003

Mitochondrial DNA sequence polymorphisms of five ethnic populations from northern China.

To study the mitochondrial DNA (mtDNA) polymorphisms in a total of 232 individuals from five ethnic populations (Daur, n=45; Ewenki, n=47; Korean, n=48; Mongolian, n=48; Oroqen, n=44) in northern China, we analyzed the control region sequences and typed for a number of characteristic mutations in coding regions (especially the region 14576-16047), by direct sequencing or restriction-fragment-length-polymorphism (RFLP) analysis. With the exception of 14 individuals belonging to the European-specific haplogroups R2, H, J, and T, the mtDNAs considered could be assigned into the East Asian-specific haplogroups described recently. The polymorphisms in cytochrome b sequence were found to be very informative for defining or supporting the haplogroups status of East Asian mtDNAs in addition to the reported regions 10171-10659 and 14055-14590 in our previous study. The haplogroup distribution frequencies varied in the five ethnic populations, but in general they all harbored a large amount of north-prevalent haplogroups, such as D, G, C, and Z, and thus were in agreement with their ethnohistory of northern origin. The two populations (Ewenki and Oroqen) with small population census also show concordant features in their matrilineal genetic structures, with lower genetic diversities observed.

Asian People↗

PubMed2003

Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences.

The now-emerging mitochondrial DNA (mtDNA) population genomics provides information for reconstructing a well-resolved mtDNA phylogeny and for discerning the phylogenetic status of the subcontinentally specific haplogroups. Although several major East Asian mtDNA haplogroups have been identified in studies elsewhere, some of the most basal haplogroups, as well as numerous minor subhaplogroups, were not yet determined or fully characterized. To fill the lacunae, we selected 48 mtDNAs from >2,000 samples across China for complete sequencing that cover virtually all (sub)haplogroups discernible to date in East Asia. This East Asian mtDNA phylogeny can henceforth serve as a solid basis for phylogeographic analyses of mtDNAs, as well as for studies of mitochondrial diseases in East and Southeast Asia.

Asia↗

PubMed2003

Mitochondrial DNA control region and cytochrome b sequence variation in the genus Mystacoleucus Günther (Pisces: Cyprinidae: Barbinae) from China.

Mitochondrial DNA (mtDNA) hypervariable segment I sequences (HVSI, 471 bp) of the control region and partial cytochrome b sequences (Cytb, 403 bp) were analyzed in three tentative species of the genus Mystacoleucus in China (M. chilopterus, M. marginatus, and M. lepturus). Not more than two mutations were found in both the HVSI and Cytb fragments among the samples from M. chilopterus and M. marginatus. However, M. lepturus differed from each of them by at least 25 mutations in Cytb and 51 mutations in HVSI. Moreover the HVSI sequence variation within M. lepturus was larger than that between M. chilopterus and M. marginatus. Given that M. chilopterus and M. marginatus are very similar in morphology, it is reasonable to consider M. chilopterus and M. marginatus as conspecific. Our results also suggest a recent radiation of M. marginatus from downstream to upstream of the Lancangjiang (Mekong) River.

Animals↗

PubMed2003

Reconstructing the evolutionary history of China: a caveat about inferences drawn from ancient DNA.

The decipherment of the meager information provided by short fragments of ancient mitochondrial DNA (mtDNA) is notoriously difficult but is regarded as a most promising way toward reconstructing the past from the genetic perspective. By haplogroup-specific hypervariable segment (HVS) motif search and matching or near-matching with available modern data sets, most of the ancient mtDNAs can be tentatively assigned to haplogroups, which are often subcontinent specific. Further typing for mtDNA haplogroup-diagnostic coding region polymorphisms, however, is indispensable for establishing the geographic/genetic affinities of ancient samples with less ambiguity. In the present study, we sequenced a fragment (approximately 982 bp) of the mtDNA control region in 76 Han individuals from Taian, Shandong, China, and we combined these data with previously reported samples from Zibo and Qingdao, Shandong. The reanalysis of two previously published ancient mtDNA population data sets from Linzi (same province) then indicates that the ancient populations had features in common with the modern populations from south China rather than any specific affinity to the European mtDNA pool. Our results highlight that ancient mtDNA data obtained under different sampling schemes and subject to potential contamination can easily create the impression of drastic spatiotemporal changes in the genetic structure of a regional population during the past few thousand years if inappropriate methods of data analysis are employed.

Asian People↗

PubMed2002

Mitochondrial DNA 5178A polymorphism and longevity.

Previous studies have shown that mitochondrial DNA (mtDNA) 5178 adenine/cytosine (5178A) polymorphism, which is one of the haplogroup-specific mutations for mtDNA haplogroup D, was apparently associated with aging and longevity in humans. We genotyped the 5178A in 293 samples representing three age groups (Old, n=95; Young, n=103; and Infant, n=95) from Yunnan Province, China. The distribution frequency of the 5178A in the Old samples (16.84%) is slightly higher than in those of the Young (13.59%) and Infant (15.79%), but the frequency difference between the age groups is far from being statistically significant ( P>0.05). Our results fail to support the suggestion of association between mtDNA 5178A (or haplogroup D) and longevity.

Adult↗

PubMed2002

Phylogeographic differentiation of mitochondrial DNA in Han Chinese.

To characterize the mitochondrial DNA (mtDNA) variation in Han Chinese from several provinces of China, we have sequenced the two hypervariable segments of the control region and the segment spanning nucleotide positions 10171-10659 of the coding region, and we have identified a number of specific coding-region mutations by direct sequencing or restriction-fragment-length-polymorphism tests. This allows us to define new haplogroups (clades of the mtDNA phylogeny) and to dissect the Han mtDNA pool on a phylogenetic basis, which is a prerequisite for any fine-grained phylogeographic analysis, the interpretation of ancient mtDNA, or future complete mtDNA sequencing efforts. Some of the haplogroups under study differ considerably in frequencies across different provinces. The southernmost provinces show more pronounced contrasts in their regional Han mtDNA pools than the central and northern provinces. These and other features of the geographical distribution of the mtDNA haplogroups observed in the Han Chinese make an initial Paleolithic colonization from south to north plausible but would suggest subsequent migration events in China that mainly proceeded from north to south and east to west. Lumping together all regional Han mtDNA pools into one fictive general mtDNA pool or choosing one or two regional Han populations to represent all Han Chinese is inappropriate for prehistoric considerations as well as for forensic purposes or medical disease studies.

Asian People↗