RESUMO
Human genomics is witnessing an ongoing paradigm shift from a single reference sequence to a pangenome form, but populations of Asian ancestry are underrepresented. Here we present data from the first phase of the Chinese Pangenome Consortium, including a collection of 116 high-quality and haplotype-phased de novo assemblies based on 58 core samples representing 36 minority Chinese ethnic groups. With an average 30.65× high-fidelity long-read sequence coverage, an average contiguity N50 of more than 35.63 megabases and an average total size of 3.01 gigabases, the CPC core assemblies add 189 million base pairs of euchromatic polymorphic sequences and 1,367 protein-coding gene duplications to GRCh38. We identified 15.9 million small variants and 78,072 structural variants, of which 5.9 million small variants and 34,223 structural variants were not reported in a recently released pangenome reference1. The Chinese Pangenome Consortium data demonstrate a remarkable increase in the discovery of novel and missing sequences when individuals are included from underrepresented minority ethnic groups. The missing reference sequences were enriched with archaic-derived alleles and genes that confer essential functions related to keratinization, response to ultraviolet radiation, DNA repair, immunological responses and lifespan, implying great potential for shedding new light on human evolution and recovering missing heritability in complex disease mapping.
Assuntos
População do Leste Asiático , Etnicidade , Variação Genética , Genoma Humano , Genética Humana , Grupos Minoritários , Humanos , População do Leste Asiático/classificação , População do Leste Asiático/genética , Etnicidade/genética , Genoma Humano/genética , Análise de Sequência de DNA , Raios Ultravioleta , Genética Humana/normas , Minorias Étnicas e Raciais , Padrões de Referência , Haplótipos/genética , Eucromatina/genética , Alelos , Reparo do DNA/genética , Queratinas/genética , Queratinas/metabolismo , Longevidade/genética , Imunidade/genéticaRESUMO
Sex-biased gene expression differs across human populations; however, the underlying genetic basis and molecular mechanisms remain largely unknown. Here, we explore the influence of ancestry on sex differences in the human transcriptome and its genetic effects on a Eurasian admixed population: Uyghurs living in Xinjiang (XJU), by analyzing whole-genome sequencing data and transcriptome data of 90 XJU and 40 unrelated Han Chinese individuals. We identified 302 sex-biased expressed genes and 174 sex-biased cis-expression quantitative loci (sb-cis-eQTLs) in XJU, which were enriched in innate immune-related functions, indicating sex differences in immunity. Notably, approximately one-quarter of the sb-cis-eQTLs showed a strong correlation with ancestry composition; i.e. populations of similar ancestry tended to show similar patterns of sex-biased gene expression. Our analysis further suggested that genetic admixture induced a moderate degree of sex-biased gene expression. Interestingly, analysis of chromosome interactions revealed that the X chromosome acted on autosomal immunity-associated genes, partially explaining the sex-biased phenotypic differences. Our work extends the knowledge of sex-biased gene expression from the perspective of genetic admixture and bridges the gap in the exploration of sex-biased phenotypes shaped by autosome and X-chromosome interactions. Notably, we demonstrated that sex chromosomes cannot fully explain sex differentiation in immune-related phenotypes.
Assuntos
População da Ásia Central , População do Leste Asiático , Locos de Características Quantitativas , Feminino , Humanos , Masculino , China , Cromossomos Humanos X/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Genética Populacional , Caracteres Sexuais , Transcriptoma , População do Leste Asiático/genética , População da Ásia Central/genéticaRESUMO
It remains unknown and debatable how European-Asian-differentiated alleles affect individual phenotypes. Here, we made the first effort to analyze the expression profiles of highly differentiated genes with eastern and western origins in 90 Uyghurs using whole-genome (30× to 60×) and transcriptome data. We screened 921 872 east-west highly differentiated genetic variants, of which â¼4.32% were expression quantitative trait loci (eQTLs), â¼0.12% were alternative splicing quantitative trait loci (sQTLs), and â¼0.12% showed allele-specific expression (ASE). The 8305 highly differentiated eQTLs of strong effects appear to have undergone natural selection, associated with immunity and metabolism. European-origin alleles tend to be more biasedly expressed; highly differentiated ASEs were enriched in diabetes-associated genes, likely affecting the diabetes susceptibility in the Uyghurs. We proposed an admixture-induced expression model to dissect the highly differentiated expression profiles. We provide new insights into the genetic basis of phenotypic differentiation between Western and Eastern populations, advancing our understanding of the impact of genetic admixture.