Deciphering Haploid Chromosome Conformation Alternation in Down Syndrome by Multiple Haploid Omics Analysis.

For chromosome abnormalities (CA), such as Down syndrome (DS), the influence of genomic variations to chromosome conformation and gene transcription remains elusive. Based on the complete genomic sequence from the parents of the DS trisomy patient, we systematically delineated an atlas of parental-specific haploid single nucleotide polymorphism (SNP), copy number variation (CNV), three-dimensional (3D) genome, and RNA expression profiles of the diencephalon in the DS patient. The integrated haploid multi-omics analysis demonstrated that one-dimensional genomic variations including SNPs and CNVs in the DS patient are highly correlated with the alterations of the 3D genome and the subsequent gene transcription. The correlation relationship remains valid in haploid-levels. Moreover, we revealed the 3D genome alteration associated mis-regulation of DS-related genes, which facilitates to understanding the pathogenesis of CA. Together, our study contributes to decipher the coding from one-dimensional genomic variations to 3D genomic architecture and the subsequent gene transcription in healthy and diseases.