Dataset Information

Significant abundance of cis configurations of coding variants in diploid human genomes.

ABSTRACT: To fully understand human genetic variation and its functional consequences, the specific distribution of variants between the two chromosomal homologues of genes must be known. The 'phase' of variants can significantly impact gene function and phenotype. To assess patterns of phase at large scale, we have analyzed 18 121 autosomal genes in 1092 statistically phased genomes from the 1000 Genomes Project and 184 experimentally phased genomes from the Personal Genome Project. Here we show that genes with cis-configurations of coding variants are more frequent than genes with trans-configurations in a genome, with global cis/trans ratios of ?60:40. Significant cis-abundance was observed in virtually all genomes in all populations. Moreover, we identified a large group of genes exhibiting cis-configurations of protein-changing variants in excess, so-called 'cis-abundant genes', and a smaller group of 'trans-abundant genes'. These two gene categories were functionally distinguishable, and exhibited strikingly different distributional patterns of protein-changing variants. Underlying these phenomena was a shared set of phase-sensitive genes of importance for adaptation and evolution. This work establishes common patterns of phase as key characteristics of diploid human exomes and provides evidence for their functional significance, highlighting the importance of phase for the interpretation of protein-coding genetic variation and gene function.

SUBMITTER: Hoehe MR

PROVIDER: S-EPMC6451136 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Significant abundance of cis configurations of coding variants in diploid human genomes.

Hoehe Margret R MR Herwig Ralf R Mao Qing Q Peters Brock A BA Drmanac Radoje R Church George M GM Huebsch Thomas T

Nucleic acids research 20190401 6

To fully understand human genetic variation and its functional consequences, the specific distribution of variants between the two chromosomal homologues of genes must be known. The 'phase' of variants can significantly impact gene function and phenotype. To assess patterns of phase at large scale, we have analyzed 18 121 autosomal genes in 1092 statistically phased genomes from the 1000 Genomes Project and 184 experimentally phased genomes from the Personal Genome Project. Here we show that gen ...[more]

PMID: 30698752

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Project description:BACKGROUND: Sugarcane (Saccharum spp.) has become an increasingly important crop for its leading role in biofuel production. The high sugar content species S. officinarum is an octoploid without known diploid or tetraploid progenitors. Commercial sugarcane cultivars are hybrids between S. officinarum and wild species S. spontaneum with ploidy at approximately 12x. The complex autopolyploid sugarcane genome has not been characterized at the DNA sequence level. RESULTS: The microsynteny between sugarcane and sorghum was assessed by comparing 454 pyrosequences of 20 sugarcane bacterial artificial chromosomes (BACs) with sorghum sequences. These 20 BACs were selected by hybridization of 1961 single copy sorghum overgo probes to the sugarcane BAC library with one sugarcane BAC corresponding to each of the 20 sorghum chromosome arms. The genic regions of the sugarcane BACs shared an average of 95.2% sequence identity with sorghum, and the sorghum genome was used as a template to order sequence contigs covering 78.2% of the 20 BAC sequences. About 53.1% of the sugarcane BAC sequences are aligned with sorghum sequence. The unaligned regions contain non-coding and repetitive sequences. Within the aligned sequences, 209 genes were annotated in sugarcane and 202 in sorghum. Seventeen genes appeared to be sugarcane-specific and all validated by sugarcane ESTs, while 12 appeared sorghum-specific but only one validated by sorghum ESTs. Twelve of the 17 sugarcane-specific genes have no match in the non-redundant protein database in GenBank, perhaps encoding proteins for sugarcane-specific processes. The sorghum orthologous regions appeared to have expanded relative to sugarcane, mostly by the increase of retrotransposons. CONCLUSIONS: The sugarcane and sorghum genomes are mostly collinear in the genic regions, and the sorghum genome can be used as a template for assembling much of the genic DNA of the autopolyploid sugarcane genome. The comparable gene density between sugarcane BACs and corresponding sorghum sequences defied the notion that polyploidy species might have faster pace of gene loss due to the redundancy of multiple alleles at each locus.

Dataset Information

Significant abundance of cis configurations of coding variants in diploid human genomes.

Publications

Significant abundance of cis configurations of coding variants in diploid human genomes.

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