PGG.SV: a whole-genome-sequencing-based structural variant resource and data analysis platform.

Structural variations (SVs) play important roles in human evolution and diseases, but there is a lack of data resources concerning representative samples, especially for East Asians. Taking advantage of both next-generation sequencing and third-generation sequencing data at the whole-genome level, we developed the database PGG.SV to provide a practical platform for both regionally and globally representative structural variants.

Haplotype-resolved de novo assembly of a Tujia genome suggests the necessity for high-quality population-specific genome references.

Even though the human reference genome assembly is continually being improved, it remains debatable whether a population-specific reference is necessary for every ethnic group. Here, we de novo assembled an individual genome (TJ1) from the Tujia population, an ethnic minority group most closely related to the Han Chinese. TJ1 provided a high-quality haplotype-resolved assembly of chromosome-scale with a scaffold N50 size >78 Mb.

Refining models of archaic admixture in Eurasia with ArchaicSeeker 2.0.

We developed a method, ArchaicSeeker 2.0, to identify introgressed hominin sequences and model multiple-wave admixture. The new method enabled us to discern two waves of introgression from both Denisovan-like and Neanderthal-like hominins in present-day Eurasian populations and an ancient Siberian individual.

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

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).

Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders.

Human genetic adaptation to high altitudes (>2500 m) has been extensively studied over the last few years, but few functional adaptive genetic variants have been identified, largely owing to the lack of deep-genome sequencing data available to previous studies. Here, we build a list of putative adaptive variants, including 63 missense, 7 loss-of-function, 1,298 evolutionarily conserved variants and 509 expression quantitative traits loci. Notably, the top signal of selection is located in , a transmembrane protein-coding gene.

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

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 comparison of allele-specific gene expression between African and European populations.

Transcriptomic diversity across human populations reflects differential regulatory mechanisms. Allelic-imbalanced gene expression is a genetic regulatory mechanism that contributes to human phenotypic variation. To systematically investigate genome-wide allele-specific expression (ASE), we analyzed RNA-Seq data from European and African populations provided by the Geuvadis project.

A missense point mutation in COL10A1 identified with whole-genome deep sequencing in a 7-generation Pakistan dwarf family.

Disease-associated variants in the human genome are continually being identified using DNA sequencing technologies that are especially effective for Mendelian disorders. Here we sequenced whole genome to high coverage (>30×) of 6 members of a 7-generation family with dwarfism from a consanguineous tribe in Pakistan to determine the causal variant(s). We identified a missense variant rs111033552 (c.

A metagenomic approach to dissect the genetic composition of enterotypes in Han Chinese and two Muslim groups.

Distinct enterotypes have been observed in the human gut but little is known about the genetic basis of the microbiome. Moreover, it is not clear how many genetic differences exist between enterotypes within or between populations. In this study, both the 16S rRNA gene and the metagenomes of the gut microbiota were sequenced from 48 Han Chinese, 48 Kazaks, and 96 Uyghurs, and taxonomies were assigned after de novo assembly.

Assessing genome-wide copy number variation in the Han Chinese population.

Background: Copy number variation (CNV) is a valuable source of genetic diversity in the human genome and a well-recognised cause of various genetic diseases. However, CNVs have been considerably under-represented in population-based studies, particularly the Han Chinese which is the largest ethnic group in the world.

Objectives: To build a representative CNV map for the Han Chinese population.

Ancestral Origins and Genetic History of Tibetan Highlanders.

The origin of Tibetans remains one of the most contentious puzzles in history, anthropology, and genetics. Analyses of deeply sequenced (30×-60×) genomes of 38 Tibetan highlanders and 39 Han Chinese lowlanders, together with available data on archaic and modern humans, allow us to comprehensively characterize the ancestral makeup of Tibetans and uncover their origins. Non-modern human sequences compose ∼6% of the Tibetan gene pool and form unique haplotypes in some genomic regions, where Denisovan-like, Neanderthal-like, ancient-Siberian-like, and unknown ancestries are entangled and elevated.

Genome-wide scans reveal variants at EDAR predominantly affecting hair straightness in Han Chinese and Uyghur populations.

Hair straightness/curliness is one of the most conspicuous features of human variation and is particularly diverse among populations. A recent genome-wide scan found common variants in the Trichohyalin (TCHH) gene that are associated with hair straightness in Europeans, but different genes might affect this phenotype in other populations. By sampling 2899 Han Chinese, we performed the first genome-wide scan of hair straightness in East Asians, and found EDAR (rs3827760) as the predominant gene (P = 4.

A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence.

Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g.

Quantitating and dating recent gene flow between European and East Asian populations.

Historical records indicate that extensive cultural, commercial and technological interaction occurred between European and Asian populations. What have been the biological consequences of these contacts in terms of gene flow? We systematically estimated gene flow between Eurasian groups using genome-wide polymorphisms from 34 populations representing Europeans, East Asians, and Central/South Asians. We identified recent gene flow between Europeans and Asians in most populations we studied, including East Asians and Northwestern Europeans, which are normally considered to be non-admixed populations.

Genetic architectures of ADME genes in five Eurasian admixed populations and implications for drug safety and efficacy.

Background: Drug absorption, distribution, metabolism and excretion (ADME) contribute to the high heterogeneity of drug responses in humans. However, the same standard for drug dosage has been applied to all populations in China although genetic differences in ADME genes are expected to exist in different ethnic groups. In particular, the ethnic minorities in northwestern China with substantial ancestry contribution from Western Eurasian people might violate such a single unified standard.

Copy number variations and genetic admixtures in three Xinjiang ethnic minority groups.

Xinjiang is geographically located in central Asia, and it has played an important historical role in connecting eastern Eurasian (EEA) and western Eurasian (WEA) people. However, human population genomic studies in this region have been largely underrepresented, especially with respect to studies of copy number variations (CNVs). Here we constructed the first CNV map of the three major ethnic minority groups, the Uyghur, Kazakh and Kirgiz, using Affymetrix Genome-Wide Human SNP Array 6.

Identification of well-differentiated gene expressions between Han Chinese and Japanese using genome-wide microarray data analysis.

Background: Investigating variations in gene expression, which can be quantitatively measured on a genome-wide scale, is essential to understand and interpret phenotypic differences among human populations. Several previous studies have examined and compared variations in gene expression between continental populations. However, differences in gene expression variation between closely related populations have not been studied yet.

A panel of ancestry informative markers to estimate and correct potential effects of population stratification in Han Chinese.

Population stratification acts as a confounding factor in genetic association studies and may lead to false-positive or false-negative results. Previous studies have analyzed the genetic substructures in Han Chinese population, the largest ethnic group in the world comprising ∼20% of the global human population. In this study, we examined 5540 Han Chinese individuals with about 1 million single-nucleotide polymorphisms (SNPs) and screened a panel of ancestry informative markers (AIMs) to facilitate the discerning and controlling of population structure in future association studies on Han Chinese.

A systematic characterization of genes underlying both complex and Mendelian diseases.

Traditionally, genetic disorders have been classified as either Mendelian diseases or complex diseases. This nosology has greatly benefited genetic counseling and the development of gene mapping strategies. However, based on two well-established databases, we identified that 54% (524 of 968) of the Mendelian disease genes were also involved in complex diseases, and this kind of genes has not been systematically analyzed.

A map of copy number variations in Chinese populations.

It has been shown that the human genome contains extensive copy number variations (CNVs). Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of them within and between populations. However, CNV study of Chinese minorities, which harbor the majority of genetic diversity of Chinese populations, has been underrepresented considering the same efforts in other populations.