Monosomy 1p36 results from a heterozygous deletion of the most distal chromosomal band on the short arm of chromosome 1. Occurring in approximately 1 in 5,000 live births, monosomy 1p36 is the most common terminal deletion observed in humans. Monosomy 1p36 is associated with mental retardation, developmental delay, hearing impairment, seizures, growth impairment, hypotonia, and heart defects. The syndrome is also characterized by several distinct dysmorphic features, including large anterior fontanels, microcephaly, brachycephaly, deep-set eyes, flat nose and nasal bridge, and pointed chin. Several genes have been proposed as causative for individual features of the phenotype. In addition, based upon molecular characterization of subjects with monosomy 1p36, several mechanisms for the generation and stabilization of terminal deletions have been proposed.
To understand better the factors contributing to keratoconus (KTCN), we performed comprehensive transcriptome profiling of human KTCN corneas for the first time using an RNA-Seq approach. Twenty-five KTCN and 25 non-KTCN corneas were enrolled in this study. After RNA extraction, total RNA libraries were prepared and sequenced. The discovery RNA-Seq analysis (in eight KTCN and eight non-KTCN corneas) was conducted first, after which the replication RNA-Seq experiment was performed on a second set of samples (17 KTCN and 17 non-KTCN corneas). Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-β, Hippo, and Wnt signaling pathways influencing corneal organization. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN.
Mosaicism refers to the presence in an individual of normal and abnormal cells that are genotypically distinct and are derived from a single zygote. The incidence of mosaicism events in the human body is underestimated as the genotypes in the mosaic ratio, especially in the low-grade mosaicism, stay unrevealed. This review summarizes various research outcomes and diagnostic questions in relation to different types of mosaicism. The impact of both tested biological material and applied method on the mosaicism detection rate is especially highlighted. As next-generation sequencing technologies constitute a promising methodological solution in mosaicism detection in the coming years, revisions in current diagnostic protocols are necessary to increase the detection rate of the unrevealed mosaicism events. Since mosaicism identification is a complex process, numerous examples of multistep mosaicism investigations are presented and discussed.
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