Genetic Admixture in the Culturally Unique Peranakan Chinese Population in Southeast Asia

The Peranakan Chinese are culturally unique descendants of immigrants from China who settled in the Malay Archipelago ∼300–500 years ago. Today, among large communities in Southeast Asia, the Peranakans have preserved Chinese traditions with strong influence from the local indigenous Malays. Yet, whether or to what extent genetic admixture co-occurred with the cultural mixture has been a topic of ongoing debate. We performed whole-genome sequencing (WGS) on 177 Singapore (SG) Peranakans and analyzed the data jointly with WGS data of Asian and European populations. We estimated that Peranakan Chinese inherited ∼5.62% (95% confidence interval [CI]: 4.76–6.49%) Malay ancestry, much higher than that in SG Chinese (1.08%, 0.65–1.51%), southern Chinese (0.86%, 0.50–1.23%), and northern Chinese (0.25%, 0.18–0.32%). A sex-biased admixture history, in which the Malay ancestry was contributed primarily by females, was supported by X chromosomal variants, and mitochondrial (MT) and Y haplogroups. Finally, we identified an ancient admixture event shared by Peranakan Chinese and SG Chinese ∼1,612 (95% CI: 1,345–1,923) years ago, coinciding with the settlement history of Han Chinese in southern China, apart from the recent admixture event with Malays unique to Peranakan Chinese ∼190 (159–213) years ago. These findings greatly advance our understanding of the dispersal history of Chinese and their interaction with indigenous populations in Southeast Asia.     

Detecting Selection in Multiple Populations by Modeling Ancestral Admixture Components

One of the most powerful and commonly used approaches for detecting local adaptation in the genome is the identification of extreme allele frequency differences between populations. In this article, we present a new maximum likelihood method for finding regions under positive selection. It is based on a Gaussian approximation to allele frequency changes and it incorporates admixture between populations. The method can analyze multiple populations simultaneously and retains power to detect selection signatures specific to ancestry components that are not representative of any extant populations. Using simulated data, we compare our method to related approaches, and show that it is orders of magnitude faster than the state-of-the-art, while retaining similar or higher power for most simulation scenarios. We also apply it to human genomic data and identify loci with extreme genetic differentiation between major geographic groups. Many of the genes identified are previously known selected loci relating to hair pigmentation and morphology, skin, and eye pigmentation. We also identify new candidate regions, including various selected loci in the Native American component of admixed Mexican-Americans. These involve diverse biological functions, such as immunity, fat distribution, food intake, vision, and hair development.     

Human-Mediated Admixture and Selection Shape the Diversity on the Modern Swine (Sus scrofa) Y Chromosomes

Throughout its distribution across Eurasia, domestic pig (Sus scrofa) populations have acquired differences through natural and artificial selection, and have often interbred. We resequenced 80 Eurasian pigs from nine different Asian and European breeds; we identify 42,288 reliable SNPs on the Y chromosome in a panel of 103 males, among which 96.1% are newly detected. Based on these new data, we elucidate the evolutionary history of pigs through the lens of the Y chromosome. We identify two highly divergent haplogroups: one present only in Asia and one fixed in Europe but present in some Asian populations. Analyzing the European haplotypes present in Asian populations, we find evidence of three independent waves of introgression from Europe to Asia in last 200 years, agreeing well with the literature and historical records. The diverse European lineages were brought in China by humans and left significant imprints not only on the autosomes but also on the Y chromosome of geographically and genetically distinct Chinese pig breeds. We also find a general excess of European ancestry on Y chromosomes relative to autosomes in Chinese pigs, an observation that cannot be explained solely by sex-biased migration and genetic drift. The European Y haplotype is associated with leaner meat production, and we hypothesize that the European Y chromosome increased in frequency in Chinese populations due to artificial selection. We find evidence of Y chromosomal gene flow between Sumatran wild boar and Chinese pigs. Our results demonstrate how human-mediated admixture and selection shaped the distribution of modern swine Y chromosomes.     

Estimating Individual Admixture Proportions from Next Generation Sequencing Data

Inference of population structure and individual ancestry is important both for population genetics and for association studies. With next generation sequencing technologies it is possible to obtain genetic data for all accessible genetic variations in the genome. Existing methods for admixture analysis rely on known genotypes. However, individual genotypes cannot be inferred from low-depth sequencing data without introducing errors. This article presents a new method for inferring an individual’s ancestry that takes the uncertainty introduced in next generation sequencing data into account. This is achieved by working directly with genotype likelihoods that contain all relevant information of the unobserved genotypes. Using simulations as well as publicly available sequencing data, we demonstrate that the presented method has great accuracy even for very low-depth data. At the same time, we demonstrate that applying existing methods to genotypes called from the same data can introduce severe biases. The presented method is implemented in the NGSadmix software available at http://www.popgen.dk/software.     

The Admixture Linkage Disequilibrium and Genetic Linkage Inference on the Gradual Admixture Population

Through the theoretical analysis of the admixture linkage disequilibrium (ALD) in the gradual admixture (GA) model, in which admixture occurs in every generation, the ALD is found to be proportional to the difference in marker allele frequencies, p₁-p₂, between two subpopulations. Based on this property, we can employ a strict monotonic function (Δ_ker=Δ/(p₁-p₂), where Δ denotes the linkage disequilibrium (LD)) of the recombination fraction between the marker locus and the disease locus to infer the true genetic linkage. We construct a quasi likelihood ratio test (LRT) for the case-only data utilizing the information of unlinked markers in the human genome. The simulation results show that our tests can be used to fine map a disease locus. The effects of parameter values in the ALD mapping are also discussed.     

渐近混合群体的混合连锁不平衡及其遗传连锁推断

在渐近混合模型中,混合现象发生在每一世代,通过对其混合连锁不平衡的理论分析,发现混合连锁不平衡与两个子群体间的基因频率差成正比。基于这一点,构造了一个对重组率严格单调的函数（△ker=△／（p1-p2）,其中△代表连锁不平衡）,进而据此推断标记基因座与疾病基因座的遗传连锁。应用人类基因组上不连锁的标记基因提供的连锁不平衡信息,基于病人组数据构造了一个准似然比统计量。模拟结果显示,此检验可用于精确的基因定位。文章亦讨论了参数对检验的影响。     

Admixture and patterns of linkage disequilibrium in a free-living vertebrate population

Linkage disequilibrium (LD), a measure of nonrandom association of alleles at different loci, is of great interest to evolutionary geneticists as it can be used to help identify loci that explain phenotypic variation. Surveys of the extent of LD across genomes have been carried out in a number of systems, most notably humans and model organisms. However, studies of natural populations of vertebrates have rarely been performed. Here, we describe an investigation of LD in a free-living island population of red deer Cervus elaphus. Relatively high levels of LD extended several tens of centimorgans, and significant LD was frequently detected between unlinked markers. The magnitude of LD varied depending on how the population was sampled. It also varied across different chromosomes, and was shown to be a function of sample size, intermarker distance and marker heterozygosity. A recent admixture event in the population led to an ephemeral increase in LD. Association mapping may be possible in this population, although a high 'baseline' level of LD could lead to false positive associations between marker loci and a trait of interest.     

Admixture analysis of a rural population of the state of Guerrero, Mexico

We studied 156 individuals of Native American descent from the city of Tlapa in the state of Guerrero in western Mexico. Most individuals' ethnicity was either Nahua, Mixtec, or Tlapanec, but self-identified Mestizos and individuals of mixed ethnicities were also included in the sample. We typed 24 autosomal, one Y-chromosome, and four mitochondrial ancestry-informative markers (AIMs) to estimate group and individual admixture proportions, and determine whether the admixture process involved directional gene flow between parental groups. When genetically defined (GD) Mestizos were excluded from the analysis, Native American ancestry represented approximately 98% of the population's gene pool, while European and West African ancestry represented approximately 1% each. Maternally inherited markers also showed an exceptionally high Native American contribution (98.5%), as did the paternally inherited marker, DYS199 (90.7%). We did not detect genetic structure in this population using these AIMs, which appears consistent with the homogeneity of the sample in terms of admixture proportions. The addition of GD Mestizos to the sample did not produce a considerable change in admixture estimates, but it had a major effect on population structure. These results show that the population of Tlapa in Guerrero, Mexico, has experienced little admixture with Europeans and/or West Africans. They also show that the impact of a small number of admixed individuals on an otherwise homogeneous population might have profound implications on subsequent ancestry/phenotype analysis and mapping strategies. We suggest that heterogeneity is a major characteristic of Mexican populations and, as a consequence, should not be disregarded when designing epidemiological studies of Mexican and Mexican American populations.     

滇牡丹天然居群的遗传多样性分析

以云南中部及西北部的6个滇牡丹(Paeonia delavayi)天然居群为研究对象,进行株高、新枝长等9个表型性状的表型多样性分析和ISSR分析。结果表明:9个表型性状变异幅度为0.9%~39.8%,平均值达到了18.9%;居群间生殖器官的变异较大,居群内营养器官更容易产生变异。利用居群间欧式距离进行聚类分析,6个居群聚为4个类群,没有与实际地理位置相吻合,说明表型特征的性状与地理距离的相关性不大。遗传多样性分析结果表明:利用筛选得到的10条引物,在取自6个自然居群、180个个体中,检测到56个多态位点。在居群水平上,多态位点百分率(PPB)为60.2%,Nei's基因多样性指数(H)和Shannon's信息指数(I)分别为0.281和0.414。在物种水平上,Nei's基因多样性指数(H)和Shannon's信息指数(I)分别为0.409和0.596。居群间的遗传分化系数(Gst)达0.319。结果显示,表型性状在居群间和居群内均存在广泛变异。滇牡丹遗传多样性水平较高,居群间遗传分化较大,滇牡丹并不濒危。     

基于分型测序技术的粒用高粱遗传多样性和群体结构分析

了解粒用高粱的遗传多样性和群体结构,能有效提高粒用高粱新品种的选育效率。本研究利用基因分型测序技术(GBS,genotyping by sequencing)对120份粒用高粱材料开展了全基因组基因分型,共获得了3456个多态性的SNP标记,其多态性信息含量指数(PIC,polymorphism information content)介于0.013～0.574之间,平均值为0.381。根据SNP标记在120份高粱材料中的基因分型数据,计算了材料间的遗传距离,其变异范围为0.084～0.613,平均遗传距离为0.365。群体进化树分析和主成分分析都将120份高粱材料划分为3个类群,类群1主要由包括美国材料MN-3609在内的亲缘关系较远的高粱材料组成,类群2主要由中国北方的高粱材料组成,类群3主要由中国南方的高粱材料组成。群体结构分析表明,当K=3时,ΔK取得最大值,说明120份高粱材料可以划分为3个类群,其划分结果与群体进化树分析和主成分分析基本一致。本研究从基因型多样性水平上阐释了粒用高粱的遗传背景和群体结构,为中国粒用高粱新品种的选育提供了理论依据。     

Whole-Genome Resequencing of Worldwide Wild and Domestic Sheep Elucidates Genetic Diversity,Introgression, and Agronomically Important Loci

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3′-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.     

Disclosing the origin and diversity of Omani cattle

Among all livestock species, cattle have a prominent status as they have contributed greatly to the economy, nutrition and culture from the beginning of farming societies until the present time. The origins and diversity of local cattle breeds have been widely assessed. However, there are still some regions for which very little of their local genetic resources is known. The present work aimed to estimate the genetic diversity and the origins of Omani cattle. Located in the south‐eastern corner of the Arabian Peninsula, close to the Near East, East Africa and the Indian subcontinent, the Sultanate of Oman occupies a key position, which may enable understanding cattle dispersal around the Indian Ocean. To disclose the origin of this cattle population, we used a set of 11 polymorphic microsatellites and 113 samples representing the European, African and Indian ancestry to compare with cattle from Oman. This study found a very heterogenic population with a markedly Bos indicus ancestry and with some degree of admixture with Bos taurus of African and Near East origin.     

Genetic characterization of Latin-American Creole cattle using microsatellite markers

Genetic diversity in and relationships among 26 Creole cattle breeds from 10 American countries were assessed using 19 microsatellites. Heterozygosities, F-statistics estimates, genetic distances, multivariate analyses and assignment tests were performed. The levels of within-breed diversity detected in Creole cattle were considerable and higher than those previously reported for European breeds, but similar to those found in other Latin American breeds. Differences among breeds accounted for 8.4% of the total genetic variability. Most breeds clustered separately when the number of pre-defined populations was 21 (the most probable K value), with the exception of some closely related breeds that shared the same cluster and others that were admixed. Despite the high genetic diversity detected, significant inbreeding was also observed within some breeds, and heterozygote excess was detected in others. These results indicate that Creoles represent important reservoirs of cattle genetic diversity and that appropriate conservation measures should be implemented for these native breeds in order to minimize inbreeding and uncontrolled crossbreeding.     

Exploiting the Extraordinary Genetic Polymorphism of Ciona for Developmental Genetics with Whole Genome Sequencing

Studies in tunicates such as Ciona have revealed new insights into the evolutionary origins of chordate development. Ciona populations are characterized by high levels of natural genetic variation, between 1 and 5%. This variation has provided abundant material for forward genetic studies. In the current study, we make use of deep sequencing and homozygosity mapping to map spontaneous mutations in outbred populations. With this method we have mapped two spontaneous developmental mutants. In Ciona intestinalis we mapped a short-tail mutation with strong phenotypic similarity to a previously identified mutant in the related species Ciona savignyi. Our bioinformatic approach mapped the mutation to a narrow interval containing a single mutated gene, α-laminin3,4,5, which is the gene previously implicated in C. savignyi. In addition, we mapped a novel genetic mutation disrupting neural tube closure in C. savignyi to a T-type Ca²⁺ channel gene. The high efficiency and unprecedented mapping resolution of our study is a powerful advantage for developmental genetics in Ciona, and may find application in other outbred species.     

Microsatellite analysis of genetic diversity and population structure of Chinese mitten crab （Eriocheir sinensis）

Chinese mitten crab (Eriocheir sinensis) has higher commercial value as food source than any other species of Eriocheir in China.To evaluate the germplasm resources and characterize the genetic diversity and population structure of the crabs in different water systems,two stocks and two farming populations were assessed with 25 polymorphic microsallite loci available in public GenBank.Basic statistics showed that the average observed heterozygosity (Ho) amongst populations ranged from 0.5789 to 0.6824.However,a remarkable presence of inbreeding and heterozygote deficiencies were observed.To analyze population structure,pairwise FST coefficients explained only ～10.3% variability from the subdivision of mitten crab populations,the remaining variability stems from the subdivision within subpopulations.Although the four populations had slight differentiation,different allelic frequencies resulted in distinct population structures.Two stocks and one farming population were clustered together to the phylogenetic branch of Yangtze crab,with an approximate membership of 95%.Whereas,another fanning population was clustered singly to the phylogenetic branch of the Liaohe crab,with a membership of 97.1%.The tests for individual admixture showed that Yangtze crab had probably been contaminated with individuals from other water systems.Genetic relationships between populations also supported the conclusion that Yangtze crab and Liaohe crab had different gene pools in spite of the origins of the same species.     

全基因组测序及其在遗传性疾病研究及诊断中的应用

最近,随着测序成本的不断降低,数据分析策略的不断提升,全基因组测序（whole-genome sequencing,WGS）已经在癌症、孟德尔遗传病、复杂疾病的致病基因检测中得到了一定运用,并逐步走向了临床诊断。全基因组测序不但可以检测编码区和非编码区的点突变（SNVs）和插入缺失（InDels）,还可以在全基因组范围内检测拷贝数变异（copy number variation,CNV）以及结构变异（structure variation,SV）。本文详细地介绍了全基因组测序的标准生物信息分析流程与方法,及其在疾病研究、临床诊断中的应用,并对全基因组测序在医学遗传学中的应用与研究进展,以及数据分析方面面临的挑战进行了概述。