Publications by authors named "Shuhua Xu"

137 Publications

Reply to Lack of evidence for a role of PIWIL1 variants in human male infertility.

Cell 2021 Apr;184(8):1943-1944

State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences-University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2021.03.003DOI Listing
April 2021

Y-LineageTracker: a high-throughput analysis framework for Y-chromosomal next-generation sequencing data.

BMC Bioinformatics 2021 Mar 9;22(1):114. Epub 2021 Mar 9.

Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Background: Y-chromosome DNA (Y-DNA) has been used for tracing paternal lineages and offers a clear path from an individual to a known, or likely, direct paternal ancestor. The advance of next-generation sequencing (NGS) technologies increasingly improves the resolution of the non-recombining region of the Y-chromosome (NRY). However, a lack of suitable computer tools prevents the use of NGS data from the Y-DNA studies.

Results: We developed Y-LineageTracker, a high-throughput analysis framework that not only utilizes state-of-the-art methodologies to automatically determine NRY haplogroups and identify microsatellite variants of Y-chromosome on a fine scale, but also optimizes comprehensive Y-DNA analysis methods for NGS data. Notably, Y-LineageTracker integrates the NRY haplogroup and Y-STR analysis modules with recognized strategies to robustly suggest an interpretation for paternal genetics and evolution. NRY haplogroup module mainly covers haplogroup classification, clustering analysis, phylogeny construction, and divergence time estimation of NRY haplogroups, and Y-STR module mainly includes Y-STR genotyping, statistical calculation, network analysis, and estimation of time to the most recent common ancestor (TMRCA) based on Y-STR haplotypes. Performance comparison indicated that Y-LineageTracker outperformed existing Y-DNA analysis tools for the high performance and satisfactory visualization effect.

Conclusions: Y-LineageTracker is an open-source and user-friendly command-line tool that provide multiple functions to efficiently analyze Y-DNA from NGS data at both Y-SNP and Y-STR level. Additionally, Y-LineageTracker supports various formats of input data and produces high-quality figures suitable for publication. Y-LineageTracker is coded with Python3 and supports Windows, Linux, and macOS platforms, and can be installed manually or via the Python Package Index (PyPI). The source code, examples, and manual of Y-LineageTracker are freely available at https://www.picb.ac.cn/PGG/resource.php or CodeOcean ( https://codeocean.com/capsule/7424381/tree ).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12859-021-04057-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941695PMC
March 2021

A genome-wide association study of facial morphology identifies novel genetic loci in Han Chinese.

J Genet Genomics 2020 Nov 9. Epub 2020 Nov 9.

Chinese Academy of Sciences Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, CAS, Shanghai, 200031, China. Electronic address:

The human face is a heritable surface with many complex sensory organs. In recent years, many genetic loci associated with facial features have been reported in different populations, yet there is a lack of studies on the Han Chinese population. Here, we report a genome-wide association study of 3D normal human faces of 2,659 Han Chinese with autosegment phenotypes of facial morphology. We identify single-nucleotide polymorphisms (SNPs) encompassing four genomic regions showing significant associations with different facial regions, including SNPs in DENND1B associated with the chin, SNPs among PISRT1 associated with eyes, SNPs between DCHS2 and SFRP2 associated with the nose, and SNPs in VPS13B associated with the nose. We replicate 24 SNPs from previously reported genetic loci in different populations, whose candidate genes are DCHS2, SUPT3H, HOXD1, SOX9, PAX3, and EDAR. These results provide a more comprehensive understanding of the genetic basis of variation in human facial morphology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgg.2020.10.004DOI Listing
November 2020

RET compound inheritance in Chinese patients with Hirschsprung disease: lack of penetrance from insufficient gene dysfunction.

Hum Genet 2021 May 12;140(5):813-825. Epub 2021 Jan 12.

Department of General Surgery, Capital Institute of Pediatrics Affiliated Children's Hospital, No. 2 Yabao Rd., Chaoyang District, Beijing, 100020, China.

Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of enteric ganglia along variable lengths of the intestine. Genetic defects play a major role in HSCR pathogenesis with nearly 50% of patients having a structural or regulatory deficiency in the major susceptibility gene RET. However, complete molecular defects remain poorly characterized in most patients. Here, we performed detailed genetic, molecular, and populational investigations of rare null mutations and modifiers at the RET locus. We first verified the pathogenicity of three RET splice site mutants (c.1879 + 1G > A, c.2607 + 5G > A and c.2608-3C > G) at the RNA level. We also identified significantly higher risk allele (genotype) frequencies, and their over-transmission, from unaffected parents to affected offspring of three functionally independent enhancer variants (rs2506030, rs7069590 and rs2435357, with odd ratios (OR) of 2.09, 2.71 and 7.59, respectively, P < 0.001). These three common variants are in significant (P < 4.64 × 10) linkage disequilibrium in the Han Chinese population with ~ 60% of them carrying at least one copy and > 10% with two copies. We show that RET compound inheritance of rare and common variants prevails in 64% (seven out of 11) of Chinese HSCR families. This study supports the idea that common RET variants can modify the penetrance of rare null RET mutations in HSCR, and the combined high susceptibility allele dosage may constitute the unique raised "risk baseline" among the Chinese population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00439-020-02247-yDOI Listing
May 2021

AdmixSim: A Forward-Time Simulator for Various Complex Scenarios of Population Admixture.

Front Genet 2020 3;11:601439. Epub 2020 Dec 3.

Key Laboratory of Computational Biology, Chinese Academy of Sciences (CAS) and Max Planck Society (MPG) Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Population admixture is a common phenomenon in humans, animals, and plants, and it plays a very important role in shaping individual genetic architecture and population genetic diversity. Inference of population admixture, however, is very challenging and typically relies on simulation. We are aware of the lack of a computerized tool for such a purpose. A simulator capable of generating data under various complex admixture scenarios would facilitate the study of recombination, linkage disequilibrium, ancestry tracing, and admixture dynamics in admixed populations. We described such a simulator here. We developed a forward-time simulator () under the standard Wright Fisher model. It can simulate the following admixed populations: (1) multiple ancestral populations; (2) multiple waves of admixture events; (3) fluctuating population size; and (4) admixtures of fluctuating proportions. Analysis of the simulated data by showed that our simulator can quickly and accurately generate data resembling real-world values. We included in all possible parameters that would allow users to modify and simulate any kind of admixture scenario easily, so it is very flexible. records recombination break points and traces of each chromosomal segment from different ancestral populations, with which users can easily perform further analysis and comparative studies with empirical data. facilitates the study of population admixture by providing a simulation framework with the flexible implementation of various admixture models and parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.601439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744625PMC
December 2020

Population genomics of East Asian ethnic groups.

Hereditas 2020 Dec 8;157(1):49. Epub 2020 Dec 8.

Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

East Asia constitutes one-fifth of the global population and exhibits substantial genetic diversity. However, genetic investigations on populations in this region have been largely under-represented compared with European populations. Nonetheless, the last decade has seen considerable efforts and progress in genome-wide genotyping and whole-genome sequencing of the East-Asian ethnic groups. Here, we review the recent studies in terms of ancestral origin, population relationship, genetic differentiation, and admixture of major East- Asian groups, such as the Chinese, Korean, and Japanese populations. We mainly focus on insights from the whole-genome sequence data and also include the recent progress based on mitochondrial DNA (mtDNA) and Y chromosome data. We further discuss the evolutionary forces driving genetic diversity in East-Asian populations, and provide our perspectives for future directions on population genetics studies, particularly on underrepresented indigenous groups in East Asia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s41065-020-00162-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724877PMC
December 2020

Shared Signature of Recent Positive Selection on the TSBP1-BTNL2-HLA-DRA Genes in Five Native Populations from North Borneo.

Genome Biol Evol 2020 12;12(12):2245-2257

Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

North Borneo (NB) is home to more than 40 native populations. These natives are believed to have undergone local adaptation in response to environmental challenges such as the mosquito-abundant tropical rainforest. We attempted to trace the footprints of natural selection from the genomic data of NB native populations using a panel of ∼2.2 million genome-wide single nucleotide polymorphisms. As a result, an ∼13-kb haplotype in the Major Histocompatibility Complex Class II region encompassing candidate genes TSBP1-BTNL2-HLA-DRA was identified to be undergoing natural selection. This putative signature of positive selection is shared among the five NB populations and is estimated to have arisen ∼5.5 thousand years (∼220 generations) ago, which coincides with the period of Austronesian expansion. Owing to the long history of endemic malaria in NB, the putative signature of positive selection is postulated to be driven by Plasmodium parasite infection. The findings of this study imply that despite high levels of genetic differentiation, the NB populations might have experienced similar local genetic adaptation resulting from stresses of the shared environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gbe/evaa207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738747PMC
December 2020

Triose Kinase Controls the Lipogenic Potential of Fructose and Dietary Tolerance.

Cell Metab 2020 10 19;32(4):605-618.e7. Epub 2020 Aug 19.

MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing 100084, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

The surge in fructose consumption is a major factor behind the rapid rise of nonalcoholic fatty liver disease in modern society. Through flux and genetic analyses, we demonstrate that fructose is catabolized at a much higher rate than glucose, and triose kinase (TK) couples fructolysis with lipogenesis metabolically and transcriptionally. In the absence of TK, fructose oxidation is accelerated through the activation of aldehyde dehydrogenase (ALDH) and serine biosynthesis, accompanied by increased oxidative stress and fructose aversion. TK is also required by the endogenous fructolysis pathway to drive lipogenesis and hepatic triglyceride accumulation under high-fat diet and leptin-deficient conditions. Intriguingly, a nonsynonymous TK allele (rs2260655_A) segregated during human migration out of Africa behaves as TK null for its inability to rescue fructose toxicity and increase hepatic triglyceride accumulation. Therefore, we posit TK as a metabolic switch controlling the lipogenic potential of fructose and its dietary tolerance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2020.07.018DOI Listing
October 2020

Radiographic study of Sever's disease.

Exp Ther Med 2020 Aug 26;20(2):933-937. Epub 2020 May 26.

Department of Radiology, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China.

X-ray and MRI differences of calcaneal epiphysis between Sever's disease patients and normal children were compared and analyzed to raise awareness of Sever's disease. A total of 98 children with Sever's disease were enrolled in the study, including 72 males and 26 females. Among them, 6 patients underwent MRI. There were 120 patients in the control group, including 73 males and 47 females, aged 8 to 15 years. The calcaneus epiphysis density (compact and cancellous bone type), the difference of the radiolucent line and the signal changes of Sever's disease on MRI of the two groups were observed and analyzed. Among the patients with Sever's disease, the male incidence rate was 79.59%, the female incidence rate was 20.41%, the average age of onset was 11.35, the average age of onset for male was 11.49, and the average age of onset for female was 10.80. There were significant statistical differences between the two groups in terms of epiphysis density (compact and cancellous type) and translucent line (χ=38.85, 137.51, P<0.05). Six cases of MRI showed partial or complete different degrees of bone marrow, ligament, soft tissue edema, and joint effusion. Sever's disease is mainly characterized by increased density of the calcaneus epiphysis and a radiolucent line of the epiphysis. It manifests as heel edema on MRI image.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2020.8796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388271PMC
August 2020

The efficacy of different treatment approaches for pediatric OSAHS patients with mandibular retrognathia: study protocol for a multicenter randomized controlled trial.

Trials 2020 Jun 30;21(1):595. Epub 2020 Jun 30.

Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.

Background: Pediatric obstructive sleep apnea/hypopnea syndrome (OSAHS) is a multifactorial syndrome caused by many risk factors, such as craniofacial anomalies, adenotonsillar hypertrophy, obesity, and airway inflammation. Although new treatment patterns have recently been proposed, treatment methods for children remain particularly challenging and controversial. This randomized controlled trial was designed to investigate the efficacy of adenotonsillectomy and/or orthodontic treatment for children who have mild OSAHS with mandibular retrognathia.

Methods: A sample of 352 children with mild OSAHS and mandibular retrognathia, who are aged between 7 and 10 years, will be enrolled in the study. They will be randomized into four groups: the drug treatment group, the surgical treatment group, the orthodontic treatment group, or the surgery and postoperative orthodontic group. After randomization the children will receive treatments within 4 weeks. Outcome assessment will take place at the following points: (1) baseline, (2) 7 months after the treatment starting point, (3) 12 months after the treatment starting point, and (4) 24 months after the treatment starting point. The primary endpoint of the trial is the mean change in obstructive apnea/hypopnea index. Other endpoints will consist of the lowest oxygen saturation, apnea index, and hypopnea index assessed by polysomnography, subjective symptoms (assessed by the OSA-20 questionnaire), cephalometric measurements, and morphologic analysis of the upper airway.

Discussion: The results of this study will provide valuable evidence for the merits and long-term efficacy of different treatment approaches and contribute to facilitating the multidisciplinary treatment of pediatric OSAHS.

Trial Registration: ClinicalTrials.gov : NCT03451318. Registered on 2 March 2018 (last update posted 19 April 2018).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-020-04398-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329444PMC
June 2020

Trio deep-sequencing does not reveal unexpected off-target and on-target mutations in Cas9-edited rhesus monkeys.

Nat Commun 2019 12 4;10(1):5525. Epub 2019 Dec 4.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223, Kunming, China.

CRISPR-Cas9 is a widely-used genome editing tool, but its off-target effect and on-target complex mutations remain a concern, especially in view of future clinical applications. Non-human primates (NHPs) share close genetic and physiological similarities with humans, making them an ideal preclinical model for developing Cas9-based therapies. However, to our knowledge no comprehensive in vivo off-target and on-target assessment has been conducted in NHPs. Here, we perform whole genome trio sequencing of Cas9-treated rhesus monkeys. We only find a small number of de novo mutations that can be explained by expected spontaneous mutations, and no unexpected off-target mutations (OTMs) were detected. Furthermore, the long-read sequencing data does not detect large structural variants in the target region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-13481-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892871PMC
December 2019

Comparative genetic architectures of schizophrenia in East Asian and European populations.

Nat Genet 2019 12 18;51(12):1670-1678. Epub 2019 Nov 18.

Psychiatric Genetic Epidemiology and Neurobiology Laboratory (PsychGENe lab), Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0512-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885121PMC
December 2019

Analysis of five deep-sequenced trio-genomes of the Peninsular Malaysia Orang Asli and North Borneo populations.

BMC Genomics 2019 Nov 12;20(1):842. Epub 2019 Nov 12.

Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Background: Recent advances in genomic technologies have facilitated genome-wide investigation of human genetic variations. However, most efforts have focused on the major populations, yet trio genomes of indigenous populations from Southeast Asia have been under-investigated.

Results: We analyzed the whole-genome deep sequencing data (~ 30×) of five native trios from Peninsular Malaysia and North Borneo, and characterized the genomic variants, including single nucleotide variants (SNVs), small insertions and deletions (indels) and copy number variants (CNVs). We discovered approximately 6.9 million SNVs, 1.2 million indels, and 9000 CNVs in the 15 samples, of which 2.7% SNVs, 2.3% indels and 22% CNVs were novel, implying the insufficient coverage of population diversity in existing databases. We identified a higher proportion of novel variants in the Orang Asli (OA) samples, i.e., the indigenous people from Peninsular Malaysia, than that of the North Bornean (NB) samples, likely due to more complex demographic history and long-time isolation of the OA groups. We used the pedigree information to identify de novo variants and estimated the autosomal mutation rates to be 0.81 × 10 - 1.33 × 10, 1.0 × 10 - 2.9 × 10, and ~ 0.001 per site per generation for SNVs, indels, and CNVs, respectively. The trio-genomes also allowed for haplotype phasing with high accuracy, which serves as references to the future genomic studies of OA and NB populations. In addition, high-frequency inherited CNVs specific to OA or NB were identified. One example is a 50-kb duplication in DEFA1B detected only in the Negrito trios, implying plausible effects on host defense against the exposure of diverse microbial in tropical rainforest environment of these hunter-gatherers. The CNVs shared between OA and NB groups were much fewer than those specific to each group. Nevertheless, we identified a 142-kb duplication in AMY1A in all the 15 samples, and this gene is associated with the high-starch diet. Moreover, novel insertions shared with archaic hominids were identified in our samples.

Conclusion: Our study presents a full catalogue of the genome variants of the native Malaysian populations, which is a complement of the genome diversity in Southeast Asians. It implies specific population history of the native inhabitants, and demonstrated the necessity of more genome sequencing efforts on the multi-ethnic native groups of Malaysia and Southeast Asia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-019-6226-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852992PMC
November 2019

YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression.

Nat Commun 2019 10 25;10(1):4892. Epub 2019 Oct 25.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.

Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan domestic mammals compared to reciprocal lowlanders. Furthermore, mA modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. Together, these findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-12801-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814821PMC
October 2019

PGG.SNV: understanding the evolutionary and medical implications of human single nucleotide variations in diverse populations.

Genome Biol 2019 10 22;20(1):215. Epub 2019 Oct 22.

Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, CAS, Shanghai, 200031, China.

Despite the tremendous growth of the DNA sequencing data in the last decade, our understanding of the human genome is still in its infancy. To understand the implications of genetic variants in the light of population genetics and molecular evolution, we developed a database, PGG.SNV ( https://www.pggsnv.org ), which gives much higher weight to previously under-investigated indigenous populations in Asia. PGG.SNV archives 265 million SNVs across 220,147 present-day genomes and 1018 ancient genomes, including 1009 newly sequenced genomes, representing 977 global populations. Moreover, estimation of population genetic diversity and evolutionary parameters is available in PGG.SNV, a unique feature compared with other databases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-019-1838-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805450PMC
October 2019

PGG.Han: the Han Chinese genome database and analysis platform.

Nucleic Acids Res 2020 01;48(D1):D971-D976

Key Laboratory of Computational Biology, Bio-Med Big Data Center, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

As the largest ethnic group in the world, the Han Chinese population is nonetheless underrepresented in global efforts to catalogue the genomic variability of natural populations. Here, we developed the PGG.Han, a population genome database to serve as the central repository for the genomic data of the Han Chinese Genome Initiative (Phase I). In its current version, the PGG.Han archives whole-genome sequences or high-density genome-wide single-nucleotide variants (SNVs) of 114 783 Han Chinese individuals (a.k.a. the Han100K), representing geographical sub-populations covering 33 of the 34 administrative divisions of China, as well as Singapore. The PGG.Han provides: (i) an interactive interface for visualization of the fine-scale genetic structure of the Han Chinese population; (ii) genome-wide allele frequencies of hierarchical sub-populations; (iii) ancestry inference for individual samples and controlling population stratification based on nested ancestry informative markers (AIMs) panels; (iv) population-structure-aware shared control data for genotype-phenotype association studies (e.g. GWASs) and (v) a Han-Chinese-specific reference panel for genotype imputation. Computational tools are implemented into the PGG.Han, and an online user-friendly interface is provided for data analysis and results visualization. The PGG.Han database is freely accessible via http://www.pgghan.org or https://www.hanchinesegenomes.org.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkz829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943055PMC
January 2020

Sex difference in kidney electrolyte transport II: impact of K intake on thiazide-sensitive cation excretion in male and female mice.

Am J Physiol Renal Physiol 2019 10 7;317(4):F967-F977. Epub 2019 Aug 7.

Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut.

We studied sex differences in response to high K (HK) intake on thiazide-sensitive cation (Na and K) excretion in wild-type (WT) and ANG II receptor subtype 1a (ATR) knockout (KO) mice. Renal clearance experiments were performed to examine Na-Cl cotransporter (NCC) activity on mice fed with control and HK (5% KCl, 7 days) diets. Hydrochlorothiazide (HCTZ)-induced changes in urine volume, glomerular filtration rate, absolute Na and K excretion, and fractional excretion were compared. HK-induced changes in NCC, Na/H exchanger isoform 3 (NHE3), and ENaC expression were examined by Western blot analysis. In WT animals under the control diet, HCTZ-induced cation excretion was greater in female animals, reflecting larger increases in Na excretion, since there was little sex difference in HCTZ-induced K excretion. Under the HK diet, the sex difference in HCTZ-induced cation excretion was reduced because of larger increments in K excretion in male animals. The fraction of K excretion was 57 ± 5% in male WT animals and 36 ± 4% in female WT animals ( < 0.05), but this difference was absent in ATR KO mice. NCC abundance was higher in female animals than in male animals but decreased by similar fractions on HK diet. NHE3 abundance decreased, whereas cleaved forms of γ-ENaC increased, with HK in all groups; these changes were similar in male and female animals and were not significantly affected by ATR ablation. These results indicate that, with the HK diet, male animals display greater distal Na delivery and greater activation of K secretion mechanisms, all suggesting a more powerful male adaptation to HK intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.00125.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843050PMC
October 2019

Combined surgical-orthodontic treatment of patients with cleidocranial dysplasia: case report and review of the literature.

Orphanet J Rare Dis 2018 12 4;13(1):217. Epub 2018 Dec 4.

Department of Oral and Craniomaxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 500, Quxi Road, Shanghai, Shanghai, China.

Objectives: To study the present treatment situation and investigate a better orthodontic approach for patients with cleidocranial dysplasia (CCD) through systematically reviewing the published cases and to conclude the surgical-orthodontic treatment experience of cleidocranial dysplasia.

Methods: A comprehensive search for studies published through to April 10, 2018 was conducted using the Pubmed, Web of Science, and Embase databases. The CCD cases treated with the approach combining surgical exposure and orthodontic treatment were concluded.

Results: Eight papers and 9 finished cases were included to be compared with the present case. The age of cases ranged from 9 to 28 years. Clearing the way of eruption path in early age can facilitate the spontaneous eruption of impacted teeth. For adults, combined surgical-orthodontic treatment can achieve a nearly complete dentition and stable occlusal contact, but it is time consuming and needs surgical assistance. The combination of orthognathic surgery can reduce the difficulty of orthodontic treatment and treatment duration, as well as achieve a better facial profile.

Conclusion: Surgical exposure combined with orthodontic traction is an effective treatment for patient with CCD. Patient's age, demand, economic circumstances, and status of permanent dentition should be considered when making treatment plan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-018-0959-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280340PMC
December 2018

AncestryPainter: A Graphic Program for Displaying Ancestry Composition of Populations and Individuals.

Genomics Proteomics Bioinformatics 2018 10 22;16(5):382-385. Epub 2018 Nov 22.

CAS Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China; Collaborative Innovation Center of Genetics and Development, Shanghai 200438, China; Human Phenome Institute, Fudan University, Shanghai 201203, China. Electronic address:

Ancestry composition of populations and individuals has been extensively investigated in recent years due to advances in the genotyping and sequencing technologies. As the number of populations and individuals used for ancestry inference increases remarkably, say more than 100 populations or 1000 individuals, it is usually challenging to present the ancestry composition in a traditional way using a rectangular graph. To address this issue, we developed a program, AncestryPainter, which can illustrate the ancestry composition of populations and individuals with a rounded and nice-looking graph to save space. Individuals are depicted as length-fixed bars partitioned into colored segments representing different ancestries, and the population of interest can be highlighted as a pie chart in the center of the circle plot. In addition, AncestryPainter can also be applied to display personal ancestry in a way similar to that for displaying population ancestry. AncestryPainter is publicly available at http://www.picb.ac.cn/PGG/resource.php.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gpb.2018.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364040PMC
October 2018

Towards broadening Forensic DNA Phenotyping beyond pigmentation: Improving the prediction of head hair shape from DNA.

Forensic Sci Int Genet 2018 11 29;37:241-251. Epub 2018 Aug 29.

University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan, Beijing, 100049, PR China; Chinese Academy of Sciences Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road Shanghai, 200031, PR China; State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Song Hu Road Shanghai, 200438, PR China.

Human head hair shape, commonly classified as straight, wavy, curly or frizzy, is an attractive target for Forensic DNA Phenotyping and other applications of human appearance prediction from DNA such as in paleogenetics. The genetic knowledge underlying head hair shape variation was recently improved by the outcome of a series of genome-wide association and replication studies in a total of 26,964 subjects, highlighting 12 loci of which 8 were novel and introducing a prediction model for Europeans based on 14 SNPs. In the present study, we evaluated the capacity of DNA-based head hair shape prediction by investigating an extended set of candidate SNP predictors and by using an independent set of samples for model validation. Prediction model building was carried out in 9674 subjects (6068 from Europe, 2899 from Asia and 707 of admixed European and Asian ancestries), used previously, by considering a novel list of 90 candidate SNPs. For model validation, genotype and phenotype data were newly collected in 2415 independent subjects (2138 Europeans and 277 non-Europeans) by applying two targeted massively parallel sequencing platforms, Ion Torrent PGM and MiSeq, or the MassARRAY platform. A binomial model was developed to predict straight vs. non-straight hair based on 32 SNPs from 26 genetic loci we identified as significantly contributing to the model. This model achieved prediction accuracies, expressed as AUC, of 0.664 in Europeans and 0.789 in non-Europeans; the statistically significant difference was explained mostly by the effect of one EDAR SNP in non-Europeans. Considering sex and age, in addition to the SNPs, slightly and insignificantly increased the prediction accuracies (AUC of 0.680 and 0.800, respectively). Based on the sample size and candidate DNA markers investigated, this study provides the most robust, validated, and accurate statistical prediction models and SNP predictor marker sets currently available for predicting head hair shape from DNA, providing the next step towards broadening Forensic DNA Phenotyping beyond pigmentation traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsigen.2018.08.017DOI Listing
November 2018

Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans.

PLoS Genet 2018 09 24;14(9):e1007640. Epub 2018 Sep 24.

Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, CA Rotterdam, The Netherlands.

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10(-10)) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10(-8)). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10(-11)) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1007640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171961PMC
September 2018

MultiWaver 2.0: modeling discrete and continuous gene flow to reconstruct complex population admixtures.

Eur J Hum Genet 2019 01 11;27(1):133-139. Epub 2018 Sep 11.

Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, CAS, Shanghai, 200031, China.

Our goal in developing the MultiWaver software series was to be able to infer population admixture history under various complex scenarios. The earlier version of MultiWaver considered only discrete admixture models. Here, we report a newly developed version, MultiWaver 2.0, that implements a more flexible framework and is capable of inferring multiple-wave admixture histories under both discrete and continuous admixture models. MultiWaver 2.0 can automatically select an optimal admixture model based on the length distribution of ancestral tracks of chromosomes, and the program can estimate the corresponding parameters under the selected model. Specifically, for discrete admixture models, we used a likelihood ratio test (LRT) to determine the optimal discrete model and an expectation-maximization algorithm to estimate the parameters. In addition, according to the principles of the Bayesian Information Criterion (BIC), we compared the optimal discrete model with several continuous admixture models. In MultiWaver 2.0, we also applied a bootstrapping technique to provide levels of support for the chosen model and the confidence interval (CI) of the estimations of admixture time. Simulation studies validated the reliability and effectiveness of our method. Finally, the program performed well when applied to real datasets of typical admixed populations, such as African Americans, Uyghurs, and Hazaras.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41431-018-0259-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303267PMC
January 2019

Mechanisms of CO Incorporation into Propargylic Amine Catalyzed by Ag(I)/Amine Catalysts.

J Org Chem 2018 Oct 18;83(19):11896-11904. Epub 2018 Sep 18.

State Key Laboratory for Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, National Engineering Laboratory for Green Chemical Productions of Alcohols, Ethers, and Esters, and Department of Chemistry, College of Chemistry and Chemical Engineering , Xiamen University , Xiamen 361005 , China.

Density functional theory calculations are carried out to explore the detail mechanisms of CO incorporation into propargylic amine catalyzed by Ag(I)/amine catalysts. Our calculations reveal that the whole reaction involves Lewis acid catalysis and Lewis base catalysis stages, and the outcomes of this reaction critically depend on the basicity of amine. A weaker base (i.e., DABCO) makes the Ag center more acidic, thus favoring the Lewis acid catalysis, resulting in benzoxazin-2-one. However, the following rearrangement of benzoxazin-2-one requires a stronger base (i.e., DBU) to stabilize its deprotonated form. Thus, the product selectivity could be subtly tuned by the choice of amine and the condition control, consistent with the experimental observations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.joc.8b01767DOI Listing
October 2018

Genome-wide variants of Eurasian facial shape differentiation and a prospective model of DNA based face prediction.

J Genet Genomics 2018 08 16;45(8):419-432. Epub 2018 Aug 16.

Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, CAS, Shanghai 200031, China. Electronic address:

It is a long-standing question as to which genes define the characteristic facial features among different ethnic groups. In this study, we use Uyghurs, an ancient admixed population to query the genetic bases why Europeans and Han Chinese look different. Facial traits were analyzed based on high-dense 3D facial images; numerous biometric spaces were examined for divergent facial features between European and Han Chinese, ranging from inter-landmark distances to dense shape geometrics. Genome-wide association studies (GWAS) were conducted on a discovery panel of Uyghurs. Six significant loci were identified, four of which, rs1868752, rs118078182, rs60159418 at or near UBASH3B, COL23A1, PCDH7 and rs17868256 were replicated in independent cohorts of Uyghurs or Southern Han Chinese. A prospective model was also developed to predict 3D faces based on top GWAS signals and tested in hypothetic forensic scenarios.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgg.2018.07.009DOI Listing
August 2018

Paternal origin of Paleo-Indians in Siberia: insights from Y-chromosome sequences.

Eur J Hum Genet 2018 11 10;26(11):1687-1696. Epub 2018 Jul 10.

MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 20043, China.

The expansion of modern humans to the American continent after the Last Glacial Maximum led the way to the present-day distribution of American aborigines. Recent advances in autosomal DNA research and expanded testing of mtDNA lineages has provided a clearer picture of the number and timing of founding lineages. However, both autosomal DNA and mtDNA research have provided unresolved competing theories between the short-term and the long-term models of the Beringian standstill hypothesis. Further, the source of founding paternal lineages of American aborigines and their relationship with ancient Siberia populations remains ambiguous. In this study, we reanalyzed a 7.0 Mbp region of 132 paternal Y-chromosome sequences, including 39 newly reported ones, of male samples from American aborigines and Eurasian populations. Among Eurasian samples, we identified Y-chromosome branches that are most closely related to known American aborigine founding lineages, that is, Q1-L804 links to Q1-M3, Q1-L330 links to Q1-Z780, Q1-M120 links to Q1-B143, and C2-F1756 links to C2-P39. The revised phylogenetic tree and age estimates indicate a narrow timeframe (~15.3-14.3 kya) for the upper time limit of human entry to the American continent. Our analysis suggests that the in situ differentiation of Q-M242 in Central Eurasia and South Siberia region gave rise to numerous sub-lineages older than 15.3 kya, and the founding of Paleo-Indian paternal lineages is part of the great Q1-L53 diffusion throughout the Eurasia after the Last Glacial Maximum. The results of our study will assist in future studies of the history of modern populations in Eurasia and the Americas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41431-018-0211-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189043PMC
November 2018

Regulation of renal Na transporters in response to dietary K.

Am J Physiol Renal Physiol 2018 10 20;315(4):F1032-F1041. Epub 2018 Jun 20.

Department of Physiology and Biophysics, Weill Medical College of Cornell University , New York, New York.

Changes in the expression of Na transport proteins were measured in the kidneys of mice with increased dietary K intake for 1 wk. The epithelial Na channel (ENaC) was upregulated, with enhanced expression of full-length and cleaved forms of α-ENaC and cleaved γ-ENaC. At the same time, the amount of the NaCl cotransporter NCC and its phosphorylated form decreased by ~50% and ~80%, respectively. The expression of the phosphorylated form of the Na-K-2Cl cotransporter NKCC2 also decreased, despite an increase in overall protein content. The effect was stronger in males (80%) than in females (40%). This implies that less Na is reabsorbed in the thick ascending limb of Henle's loop and distal convoluted tubule along with Cl, whereas more is reabsorbed in the aldosterone-sensitive distal nephron in exchange for secreted K. The abundance of the proximal tubule Na/H exchanger NHE3 decreased by ~40%, with similar effects in males and females. Time-course studies indicated that NCC and NHE3 proteins decreased progressively over 7 days on a high-K diet. Expression of mRNA encoding these proteins increased, implying that the decreased protein levels resulted from decreased rates of synthesis or increased rates of degradation. The potential importance of changes in NHE3, NKCC2, and NCC in promoting K excretion was assessed with a mathematical model. Simulations indicated that decreased NHE3 produced the largest effect. Regulation of proximal tubule Na transport may play a significant role in achieving K homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.00117.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230734PMC
October 2018

Genetic structure, divergence and admixture of Han Chinese, Japanese and Korean populations.

Hereditas 2018 6;155:19. Epub 2018 Apr 6.

1Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.

Background: Han Chinese, Japanese and Korean, the three major ethnic groups of East Asia, share many similarities in appearance, language and culture etc., but their genetic relationships, divergence times and subsequent genetic exchanges have not been well studied.

Results: We conducted a genome-wide study and evaluated the population structure of 182 Han Chinese, 90 Japanese and 100 Korean individuals, together with the data of 630 individuals representing 8 populations wordwide. Our analyses revealed that Han Chinese, Japanese and Korean populations have distinct genetic makeup and can be well distinguished based on either the genome wide data or a panel of ancestry informative markers (AIMs). Their genetic structure corresponds well to their geographical distributions, indicating geographical isolation played a critical role in driving population differentiation in East Asia. The most recent common ancestor of the three populations was dated back to 3000 ~ 3600 years ago. Our analyses also revealed substantial admixture within the three populations which occurred subsequent to initial splits, and distinct gene introgression from surrounding populations, of which northern ancestral component is dominant.

Conclusions: These estimations and findings facilitate to understanding population history and mechanism of human genetic diversity in East Asia, and have implications for both evolutionary and medical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s41065-018-0057-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889524PMC
April 2018

Genetic relatedness of indigenous ethnic groups in northern Borneo to neighboring populations from Southeast Asia, as inferred from genome-wide SNP data.

Ann Hum Genet 2018 07 9;82(4):216-226. Epub 2018 Mar 9.

Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, Sabah, Malaysia.

The region of northern Borneo is home to the current state of Sabah, Malaysia. It is located closest to the southern Philippine islands and may have served as a viaduct for ancient human migration onto or off of Borneo Island. In this study, five indigenous ethnic groups from Sabah were subjected to genome-wide SNP genotyping. These individuals represent the "North Borneo"-speaking group of the great Austronesian family. They have traditionally resided in the inland region of Sabah. The dataset was merged with public datasets, and the genetic relatedness of these groups to neighboring populations from the islands of Southeast Asia, mainland Southeast Asia and southern China was inferred. Genetic structure analysis revealed that these groups formed a genetic cluster that was independent of the clusters of neighboring populations. Additionally, these groups exhibited near-absolute proportions of a genetic component that is also common among Austronesians from Taiwan and the Philippines. They showed no genetic admixture with Austro-Melanesian populations. Furthermore, phylogenetic analysis showed that they are closely related to non-Austro-Melansian Filipinos as well as to Taiwan natives but are distantly related to populations from mainland Southeast Asia. Relatively lower heterozygosity and higher pairwise genetic differentiation index (F ) values than those of nearby populations indicate that these groups might have experienced genetic drift in the past, resulting in their differentiation from other Austronesians. Subsequent formal testing suggested that these populations have received no gene flow from neighboring populations. Taken together, these results imply that the indigenous ethnic groups of northern Borneo shared a common ancestor with Taiwan natives and non-Austro-Melanesian Filipinos and then isolated themselves on the inland of Sabah. This isolation presumably led to no admixture with other populations, and these individuals therefore underwent strong genetic differentiation. This report contributes to addressing the paucity of genetic data on representatives from this strategic region of ancient human migration event(s).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ahg.12246DOI Listing
July 2018

A genome-wide characterization of copy number variations in native populations of Peninsular Malaysia.

Eur J Hum Genet 2018 06 23;26(6):886-897. Epub 2018 Feb 23.

Chinese Academy of Sciences (CAS), Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Shanghai, 200031, China.

Copy number variations (CNVs) are genomic structural variations that result from the deletion or duplication of large genomic segments. The characterization of CNVs is largely underrepresented, particularly those of indigenous populations, such as the Orang Asli in Peninsular Malaysia. In the present study, we first characterized the genome-wide CNVs of four major native populations from Peninsular Malaysia, including the Malays and three Orang Asli populations; namely, Proto-Malay, Senoi, and Negrito (collectively called PM). We subsequently assessed the distribution of CNVs across the four populations. The resulting global CNV map revealed 3102 CNVs, with an average of more than 100 CNVs per individual. We identified genes harboring CNVs that are highly differentiated between PM and global populations, indicating that these genes are predominantly enriched in immune responses and defense functions, including APOBEC3A_B, beta-defensin genes, and CCL3L1, followed by other biological functions, such as drug and toxin metabolism and responses to radiation, suggesting some attributions between CNV variations and adaptations of the PM groups to the local environmental conditions of tropical rainforests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41431-018-0120-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974366PMC
June 2018

Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia.

Hum Genet 2018 Feb 30;137(2):161-173. Epub 2018 Jan 30.

Faculty of Medicine and Health Sciences, UCSI University, Jalan Menara Gading, Taman Connaught, Cheras, 56000, Kuala Lumpur, Malaysia.

Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00439-018-1869-0DOI Listing
February 2018