Constitutional Cytogenetic Review of a Familial Genome using Nexus Copy Number 7 – Osteogenesis Imperfecta Case Study

Scope

The purpose of this white paper is to give an overview of using Nexus Copy Number 7 in cytogeneticcase review, integrating copy number and sequence variant data across familial genomes. Data(Osteogenesis Imperfecta case) used in these analyses were retrieved from the NCBI GEO database(Martinez-Galez et. al., accession #GSE21958).

Overview of typical workflow used in case

Case Review SchematicAs a first step, raw data from arrays, or alignmentdata from sequencing platforms (BAM format), arepre-processed, and the log-ratio of signal-intensity values for DNA content at each measured locus ascompared to the reference baseline is calculated. The log-ratio data are then segmented using analgorithm (see theNotessection), and copy number changes are derived.As a next step, sequence variation data for each sample can be loaded into Nexus. The data can be ineither MAF or VCF format. This can be from whole-genome, whole-exome, or targeted sequencing. Thesequence variation coverage does not have to correspond to the structural variation coverage, whichallows for genome-wide structural variants to be mapped against more narrow sequence variation.Lastly, the combined data can be reviewed and individual aberrant events (either by region or gene) canbe queried against reference data for healthy (e.g., DGV) or disease (e.g., dbVAR, TCGA) populations.Inthis white paper, we further explore combining separate samples from related individuals to rapidly arrive at pathogenic genetic changes.

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