RESUMEN
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.
Asunto(s)
Pueblos del Este de Asia , Etnicidad , Variación Genética , Genoma Humano , Genética Humana , Grupos Minoritarios , Humanos , Pueblos del Este de Asia/clasificación , Pueblos del Este de Asia/genética , Etnicidad/genética , Genoma Humano/genética , Análisis de Secuencia de ADN , Rayos Ultravioleta , Genética Humana/normas , Minorías Étnicas y Raciales , Estándares de Referencia , Haplotipos/genética , Eucromatina/genética , Alelos , Reparación del ADN/genética , Queratinas/genética , Queratinas/metabolismo , Longevidad/genética , Inmunidad/genéticaRESUMEN
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.
