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BMC Genomics

, 17:225

Human and rodent genomics

Abstract

BackgroundThe role of random mutations and genetic errors in defining the etiology of cancer and other multigenic diseases has recently received much attention. With the view that complex genes should be particularly vulnerable to such events, here we explore the link between the simple properties of the human genes, such as transcript length, number of splice variants, exon-intron composition, and their involvement in the pathways linked to cancer and other multigenic diseases.

ResultsWe reveal a substantial enrichment of cancer pathways with long genes and genes that have multiple splice variants. Although the latter two factors are interdependent, we show that the overall gene length and splicing complexity increase in cancer pathways in a partially decoupled manner. Our systematic survey for the pathways enriched with top lengthy genes and with genes that have multiple splice variants reveal, along with cancer pathways, the pathways involved in various neuronal processes, cardiomyopathies and type II diabetes. We outline a correlation between the gene length and the number of somatic mutations.

ConclusionsOur work is a step forward in the assessment of the role of simple gene characteristics in cancer and a wider range of multigenic diseases. We demonstrate a significant accumulation of long genes and genes with multiple splice variants in pathways of multigenic diseases that have already been associated with de novo mutations. Unlike the cancer pathways, we note that the pathways of neuronal processes, cardiomyopathies and type II diabetes contain genes long enough for topoisomerase-dependent gene expression to also be a potential contributing factor in the emergence of pathologies, should topoisomerases become impaired.

KeywordsLong genes Splice variants Cancer Multigenic diseases KEGG pathways Mutations Topoisomerases Abbreviations2D2-dimensional

ASDAutism spectrum disorder

CDSCoding sequence

COSMICCatalogue of somatic mutations in cancer

GOGene ontology

KEGGKyoto encyclopaedia of genes and genomes

ntNucleotide

UTRUntranslated region

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-016-2582-9 contains supplementary material, which is available to authorized users.

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Autor: Aleksandr B. Sahakyan - Shankar Balasubramanian

Fuente: https://link.springer.com/







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