Mitogenome evidence shows two radiation events and dispersals of matrilineal ancestry from northern coastal China to the Americas and Japan.

Although it is widely recognized that the ancestors of Native Americans (NAs) primarily came from Siberia, the link between mitochondrial DNA (mtDNA) lineage D4h3a (typical of NAs) and D4h3b (found so far only in East China and Thailand) raises the possibility that the ancestral sources for early NAs were more variegated than hypothesized. Here, we analyze 216 contemporary (including 106 newly sequenced) D4h mitogenomes and 39 previously reported ancient D4h data. The results reveal two radiation events of D4h in northern coastal China, one during the Last Glacial Maximum and the other within the last deglaciation, which facilitated the dispersals of D4h sub-branches to different areas including the Americas and the Japanese archipelago. The coastal distributions of the NA (D4h3a) and Japanese lineages (D4h1a and D4h2), in combination with the Paleolithic archaeological similarities among Northern China, the Americas, and Japan, lend support to the coastal dispersal scenario of early NAs.

Interlaboratory method validation of slope ratio determination for anticoagulant activity of leeches / 中国药理学通报

Aim To investigate the slope ratio method for the determination of anticoagulant activity of leeches. Methods Three batches of leeches, four groups of Japanese medical vermiculite yinpian and fifteen groups of leech preparations were chosen, with contrast medicinal leeches herbs and Philippine cattle leech contrast medicinal materials, and different concentrations of leaching solutions were prepared in parallel. APTT value was determined after anticoagulant activity was determined by slope ratio method for the joint validation of laboratory, intermediate precision and accuracy between the linear range. Results The slope ratio method was accurate and accurate in the determination of anticoagulant activity of leeches, with linearity between 64% and 156% relative titer level. Conclusion Slope ratio method can be used to determine the anticoagulant activity of leeches.

Complete mitogenomes document substantial genetic contribution from the Eurasian Steppe into northern Pakistani Indo-Iranian speakers.

To elucidate whether Bronze Age population dispersals from the Eurasian Steppe to South Asia contributed to the gene pool of Indo-Iranian-speaking groups, we analyzed 19,568 mitochondrial DNA (mtDNA) sequences from northern Pakistani and surrounding populations, including 213 newly generated mitochondrial genomes (mitogenomes) from Iranian and Dardic groups, both speakers from the ancient Indo-Iranian branch in northern Pakistan. Our results showed that 23% of mtDNA lineages with west Eurasian origin arose in situ in northern Pakistan since ~5000 years ago (kya), a time depth very close to the documented Indo-European dispersals into South Asia during the Bronze Age. Together with ancient mitogenomes from western Eurasia since the Neolithic, we identified five haplogroups (~8.4% of maternal gene pool) with roots in the Steppe region and subbranches arising (age ~5-2 kya old) in northern Pakistan as genetic legacies of Indo-Iranian speakers. Some of these haplogroups, such as W3a1b that have been found in the ancient samples from the late Bronze Age to the Iron Age period individuals of Swat Valley northern Pakistan, even have sub-lineages (age ~4 kya old) in the southern subcontinent, consistent with the southward spread of Indo-Iranian languages. By showing that substantial genetic components of Indo-Iranian speakers in northern Pakistan can be traced to Bronze Age in the Steppe region, our study suggests a demographic link with the spread of Indo-Iranian languages, and further highlights the corridor role of northern Pakistan in the southward dispersal of Indo-Iranian-speaking groups.

Exploring European ancestry among the Kalash population: a mitogenomic perspective.

With a population of around 4 000 individuals, the Kalash people have been living in the Hindu-Kush mountain valleys of present-day northern Pakistan for centuries. Due to their mysterious origin and fairer European complexion, the genetic history of this ethnic group has been investigated previously using different markers. To date, however, the maternal genetic architecture has not been systematically dissected based on high-resolution complete mitochondrial genomes (mitogenomes), making their maternal genetic history, especially their genetic connection with Europeans from a matrilineal perspective, unclear. To unravel this issue, we analyzed mitogenome data of 34 Kalash samples together with 6 075 individuals from across Eurasia. Our results indicated exclusive western Eurasian origin of the Kalash people, represented by eight haplogroups. Among these haplogroups, J2b1a7a and R0a5a (accounting for ~50% of the Kalash gene pool) displayed in situ differentiations in the Kalash and could be traced to the Mediterranean region. Age estimations suggested these haplogroups arose in the Kalash population ~2.26 and 3.01 thousand years ago (kya), a time frame consistent with the invasion of Alexander III of Macedon to the region. One possible explanation for the maternal genetic contribution from Europeans to the Kalash people would be the involvement of women in foreign campaigns of ancient Greek warfare, followed by a founder effect. Our study thus sheds important light on the genetic origin of the Kalash community of Pakistan.

River Valleys Shaped the Maternal Genetic Landscape of Han Chinese.

A general south-north genetic divergence has been observed among Han Chinese in previous studies. However, these studies, especially those on mitochondrial DNA (mtDNA), are based either on partial mtDNA sequences or on limited samples. Given that Han Chinese comprise the world's largest population and reside around the whole China, whether the north-south divergence can be observed after all regional populations are considered remains unknown. Moreover, factors involved in shaping the genetic landscape of Han Chinese need further investigation. In this study, we dissected the matrilineal landscape of Han Chinese by studying 4,004 mtDNA haplogroup-defining variants in 21,668 Han samples from virtually all provinces in China. Our results confirmed the genetic divergence between southern and northern Han populations. However, we found a significant genetic divergence among populations from the three main river systems, that is, the Yangtze, the Yellow, and the Zhujiang (Pearl) rivers, which largely attributed to the prevalent distribution of haplogroups D4, B4, and M7 in these river valleys. Further analyses based on 4,986 mitogenomes, including 218 newly generated sequences, indicated that this divergence was already established during the early Holocene and may have resulted from population expansion facilitated by ancient agricultures along these rivers. These results imply that the maternal gene pools of the contemporary Han populations have retained the genetic imprint of early Neolithic farmers from different river basins, or that river valleys represented relative migration barriers that facilitated genetic differentiation, thus highlighting the importance of the three ancient agricultures in shaping the genetic landscape of the Han Chinese.

Neolithic millet farmers contributed to the permanent settlement of the Tibetan Plateau by adopting barley agriculture.

The permanent human settlement of the Tibetan Plateau (TP) has been suggested to have been facilitated by the introduction of barley agriculture ∼3.6 kilo-years ago (ka). However, how barley agriculture spread onto the TP remains unknown. Given that the lower altitudes in the northeastern TP were occupied by millet cultivators from 5.2 ka, who also adopted barley farming ∼4 ka, it is highly possible that it was millet farmers who brought barley agriculture onto the TP ∼3.6 ka. To test this hypothesis, we analyzed mitochondrial DNA (mtDNA) from 8277 Tibetans and 58 514 individuals from surrounding populations, including 682 newly sequenced whole mitogenomes. Multiple lines of evidence, together with radiocarbon dating of cereal remains at different elevations, supports the scenario that two haplogroups (M9a1a1c1b1a and A11a1a), which are common in contemporary Tibetans (20.9%) and were probably even more common (40-50%) in early Tibetans prior to historical immigrations to the TP, represent the genetic legacy of the Neolithic millet farmers. Both haplogroups originated in northern China between 10.0-6.0 ka and differentiated in the ancestors of modern Tibetans ∼5.2-4.0 ka, matching the dispersal history of millet farming. By showing that substantial genetic components in contemporary Tibetans can trace their ancestry back to the Neolithic millet farmers, our study reveals that millet farmers adopted and brought barley agriculture to the TP ∼3.6-3.3 ka, and made an important contribution to the Tibetan gene pool.

[The origin and evolution history of East Asian populations from genetic perspectives].

East Asia is widely concerned as one of the important places for the dispersal and evolution of the Anatomically Modern Human (AMH). How the diverse ethnic groups in East Asia originated and diversified is also widely focused by different disciplines of Anthropology. The adoption of genetic data had provided new clues for reconstructing the genetic history of East Asian populations. Genetic studies supported the hypothesis that the AMHs originated from Africa's Homo sapiens at about 200 kilo years ago (kya) and then migrated out of Africa at ~100 kya, followed by expansions into the whole East Asia since their arrival in Southern East Asia at 5~6 kya along the coastal route. Early Homo Sapiens might have genetic contribution to the non-African AMHs. Early settlement, cultural assimilation, population migration and genetic exchanges are crucial in the origination and evolution of East Asia populations. Previous studies made detailed analysis for the genetic history of East Asian populations, which largely resolved the longstanding divergence between archaeology and history. However, this needs further verification by whole-genome sequencing and ancient DNA studies. Here we briefly reviewed the progresses of genetic studies in exploring the population origin, dispersal and diversification in East Asia, which improved understanding of the evolution of East Asian populations. We also prospected the future of genetic studies in revealing the prehistory of East Asians.

Cultural diffusion of Indo-Aryan languages into Bangladesh: A perspective from mitochondrial DNA.

Although both linguistic and historical studies indicated only a small group of Aryans had been involved into the diffusion of Indo-Aryan languages into Bangladesh, no genetic studies had been carried out to prove this notion. By studying mitochondrial DNA variants of 240 Bengali speakers in Bangladesh, among which 23 mitogenomes are completely sequenced, we found a high proportion of South Asian components in this group. By contrast, only a small proportion of lineages can be traced back to western Eurasia, which could be attributed to recent gene flow. Our results implied a cultural diffusion of the Indo-Aryan languages into Bangladesh.

Mitochondrial DNA plays an equal role in influencing female and male longevity in centenarians.

The mitochondrion is a double membrane-bound organelle which plays important functional roles in aging and many other complex phenotypes. Transmission of the mitochondrial genome in the matrilineal line causes the evolutionary selection sieve only in females. Theoretically, beneficial or neutral variations are more likely to accumulate and be retained in the female mitochondrial genome during evolution, which may be an initial trigger of gender dimorphism in aging. The asymmetry of evolutionary processes between gender could lead to males and females aging in different ways. If so, gender specific variation loads could be an evolutionary result of maternal heritage of mitochondrial genomes, especially in centenarians who live to an extreme age and are considered as good models for healthy aging. Here, we tested whether the mitochondrial variation loads were associated with altered aging patterns by investigating the mtDNA haplogroup distribution and genetic diversity between female and male centenarians. We found no evidence of differences in aging patterns between genders in centenarians. Our results indicate that the evolutionary consequence of gender dimorphism in mitochondrial genomes is not a factor in the altered aging patterns in human, and that mitochondrial DNA contributes equally to longevity in males and females.

Exploring the maternal history of the Tai people.

In the past decades, the Tai people are increasingly being focused by genetic studies. However, a systematic genetic study of the whole Tai people is still lacking, thus making the population structure as well as the demographic history of this group uninvestigated from genetic perspective. Here we extensively analyzed the variants of hypervariable segments I and II (HVS-I and HVS-II) of mitochondrial DNA (mtDNA) of 719 Tai samples from 19 populations, covering virtually all of the current Tai people's residences. We observed a general close genetic affinity of the Tai people, reflecting a common origin of this group. Taken into account the phylogeographic analyses of their shared components, including haplogroups F1a, M7b and B5a, our study supported a southern Yunnan origin of the Tai people, consistent with the historical records. In line with their diverse cultures and languages, substantial genetic divergences can be observed among different Tai populations that could be attributable to assimilation of maternal components from neighboring populations. Our study further implied the advent of rice agriculture in Mainland Southeast Asia at ∼5 kya (kilo years ago) had greatly promoted the population expansion of the Tai people.

Ancient inland human dispersals from Myanmar into interior East Asia since the Late Pleistocene.

Given the existence of plenty of river valleys connecting Southeast and East Asia, it is possible that some inland route(s) might have been adopted by the initial settlers to migrate into the interior of East Asia. Here we analyzed mitochondrial DNA (mtDNA) HVS variants of 845 newly collected individuals from 14 Myanmar populations and 5,907 published individuals from 115 populations from Myanmar and its surroundings. Enrichment of basal lineages with the highest genetic diversity in Myanmar suggests that Myanmar was likely one of the differentiation centers of the early modern humans. Intriguingly, some haplogroups were shared merely between Myanmar and southwestern China, hinting certain genetic connection between both regions. Further analyses revealed that such connection was in fact attributed to both recent gene flow and certain ancient dispersals from Myanmar to southwestern China during 25-10 kya, suggesting that, besides the coastal route, the early modern humans also adopted an inland dispersal route to populate the interior of East Asia.

A genetic contribution from the Far East into Ashkenazi Jews via the ancient Silk Road.

Contemporary Jews retain a genetic imprint from their Near Eastern ancestry, but obtained substantial genetic components from their neighboring populations during their history. Whether they received any genetic contribution from the Far East remains unknown, but frequent communication with the Chinese has been observed since the Silk Road period. To address this issue, mitochondrial DNA (mtDNA) variation from 55,595 Eurasians are analyzed. The existence of some eastern Eurasian haplotypes in eastern Ashkenazi Jews supports an East Asian genetic contribution, likely from Chinese. Further evidence indicates that this connection can be attributed to a gene flow event that occurred less than 1.4 kilo-years ago (kya), which falls within the time frame of the Silk Road scenario and fits well with historical records and archaeological discoveries. This observed genetic contribution from Chinese to Ashkenazi Jews demonstrates that the historical exchange between Ashkenazim and the Far East was not confined to the cultural sphere but also extended to an exchange of genes.

Clinical features of a Chinese infant with inborn error of bile acid metabolism-3β-hydroxy-Δ(5)-C27-steroid dehydrogenase deficiency and review of the literature / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the clinical features of children with 3β-hydroxy-Δ(5)-C27-steroid dehydrogenase deficiency and review the literature.</p><p><b>METHOD</b>Clinical features and treatment of one Chinese infant with 3β-hydroxy-Δ(5)-C27-steroid dehydrogenase deficiency confirmed by HSD3B7 gene mutation analysis were retrospectively reviewed, and 51 cases of 3β-hydroxy-Δ(5)-C27-steroid dehydrogenase deficiency who were internationally reported since 2000 were also reviewed in this paper.</p><p><b>RESULT</b>(1) A 3-month-old infant with neonatal cholestasis was admitted to our hospital because of hyperbilirubinemia and abnormal liver dysfunction (total bilirubin 110.7 µmol/L, direct bilirubin 74.5 µmol/L, γ-glutamyltransferase 24.4 IU/L, total bile acid 0.1 µmol/L).His jaundice disappeared within a few weeks, serum liver biochemistries improved and his growth in weight and height was excellent after oral cholic acid therapy.HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patient identified compound heterozygous mutations. This child was confirmed as the most common inborn error of bile acid metabolism-3β-hydroxy-Δ(5)-C27-steroid dehydrogenase deficiency by molecular analysis.(2) Retrospective review of the literature showed that the clinical features of 3β-hydroxy-Δ(5)-C27-steroid dehydrogenase deficiency included neonatal cholestasis, some patients progressed to severe liver disease and needed liver transplantation without effective therapy; however, serum biochemical characteristics of normal γ-glutamyltransferase activity, normal or low total bile acid concentrations were not consistent with cholestasis, the replacement treatment with cholic acid produced a dramatic improvements in symptoms, biochemical markers of liver injury; 31 cases were diagnosed by HSD3B7 gene mutation analysis.</p><p><b>CONCLUSION</b>The clinical characteristics of 3β-hydroxy-Δ(5)-C27-steroid dehydrogenase deficiency include neonatal cholestasis, normal serum γ-glutamyltransferase activity, and normal or low serum total bile acid concentration.Oral cholic acid replacement is an effective therapy; definitive diagnosis of 3β-hydroxy-Δ(5)-C27-steroid dehydrogenase deficiency can be identified by molecular genetic testing technology.</p>

Clinical analysis of children with severe hand-foot-and-mouth disease in Shanghai / 中华儿科杂志

<p><b>OBJECTIVE</b>To retrospectively analyzed the clinical features and epidemiology of children with severe hand-foot-and-mouth disease during 2009 and 2010 in Shanghai to investigate some risk factors with fatal cases.</p><p><b>METHOD</b>All the clinical records and laboratory results of serious patients were collected. A retrospective study was performed.</p><p><b>RESULT</b>A total of 748 serious patients were enrolled into this study, and the ratio of male to female was about 1.7:1; 724 patients were categorized into stage 2 with 254 patients in 2009 and 470 in 2010; 24 patients were categorized into stage 3 with 17 in 2009 and 7 in 2010. The rate of severity in 2010 (1.5%) was lower than in 2009 (6.3%) (χ2=12.836, P<0.01). Seven patients of stage 3 died, with the fatality 29.2%, which was higher than in stage 2 (P<0.01). The children aged between 3 months 10 days to 12 years 9 months with onset median age of 25 months. Among them, 77.1% patients aged between 1 and 4 years which also accounted for 79.2% of the fatal cases (19/24). But there was no significant difference between the age and the severity (χ2=0.804, P>0.05). Fever (100%), vomiting (57.0%) and myoclonus jerk (62.3%) were the most frequent symptoms occurred in those serious cases. The average period of fever in children of stage 2 and 3 was (4.10±1.40) d and (5.05±1.05) d, respectively, which indicated significant difference between the two groups (t=3.173, P<0.05). The average values of white-blood-cell counts and blood glucose in fatal patients were (14.8±6.25)×10(9)/L and (8.63±3.51) mmol/L. They were higher when compared to those in stage 2 with the white-blood-cell counts of (11.8±4.23)×10(9)/L and blood glucose of (5.51±2.14) mmol/L (P<0.05). But there was no significant difference in C-reactive protein or cerebrospinal fluid white-blood-cell counts; A total of 182 patients were enrolled for MRI study during the acute stage with 37 (37/182, 20.3%) presented abnormal findings. Among them, most frequent findings were hyperintense lesions seen in brain stem (11 cases). A stage 3 case who died presented brain edema on MRI examination.</p><p><b>CONCLUSION</b>The epidemic of HFMD has some correlation with the area, season, health condition of the family and gender of the children. Children under 4 years of age especially those who lived in rural areas were susceptible to the HFMD. Frequent vomiting or myoclonus jerk may indicate the central nervous system involvement. But persistent high fever may indicate tendency to deteriorate. Some laboratory examinations can help find the fatal cases at an early time.</p>

Clinical Cross Sectional Study of Herpes Simplex Virus Infection of Central Nervous System in Newborn Infants / 实用儿科临床杂志

Objective To investigate the prevalence of herpes simplex virus(HSV) infection of central nervous system(CNS) in newborn infant,and analyze its clinical characteristics.Methods Cerebrospinal fluid(CSF) was collected from 40 acute viral infection of central nervous system who were hospitalized during June 2001 to June 2002.Polymerse chain reacton techniques(nested-PCR)was used to detect HSVspecific DNA in CSF,enzyme-linked immunosorbert assays(ELISA)was applied to detect HSV-specific IgM and IgG antibody in CSF and serum specimens.Results Two cases of neonatal patients were HSV-1 DNA PCR positive in CSF,both(mo)-ther were normal during pregnancy without a history of genital herpes.Clinical presentations of one case belonged to disseminated HSV infections and the other was limited to CNS infections.HSV-2 DNA PCR of 40 cases of neonatal patients were negative in CSF.Conclusions The rate of HSV neonatal CNS infection was 5% among viral neonatal CNS infections.HSV type 1 in the period,which showed that HSV type 1 may be the common type of HSV neonatal CNS infections.The result seems to be related to low prevalence for HSV-2(among) pregnancy women in China.