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High Resolution Copy Number Analysis of Parkinson’s

Samples Using Nexus Copy Number and Roche

NimbleGen Microarrays

A WHITE PAPER FROM

BioDiscovery, Inc. and Roche NimbleGen, Inc.

September 2008

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BioDiscovery Inc. Roche NimbleGen, Inc.

BioDiscovery Tel: 310-414-8100 | Roche NimbleGen Tel: +1 608-218-7600 Page 2

Introduction

The goal of this study was to utilize high-resolution comparative genomic hybridization (CGH)

technologies to identify functional mutations associated with Parkinson’s disease. Results from this

study identified a disease-causing microdeletion within the PARK2 gene in an affected individual. The

data for this study was generously provided by Dr. Christopher E. Mason of Yale Medical School working

in Dr. Matthew State’s laboratory. The details of the study have been published in Human Mutation

(2007 Dec; 28(12):1236-40).

Genomic DNA from an affected patient was prepared and co-hybridized with normal human genomic

DNA (pool of 6 individuals) on two different NimbleGenTM 385K arrays. The first array was the Human

CGH 385K Whole-Genome Tiling catalog array (6270bp median probe spacing) provided by Roche

NimbleGen, Inc. The second array was a focused Human Chromosome 6-specific array consisting of 385K

probes (404bp median probe spacing). We processed both arrays using Nexus Copy NumberTM

Professional version 3.1 and report the findings below.

Identification of a PARK2 Deletion

The raw data were normalized using Roche NimbleGen’s NimbleScanTM software and subsequently

processed in Nexus Copy NumberTM using the built-in Rank Segmentation algorithm. Identical

parameters were set for both the “Whole-Genome” and the “Focused” arrays. As shown in figure 1,

both samples show a common deletion on chromosome 6. It is also interesting to note that the higher- resolution focused array (Array 104418) identified additional copy number changes on chromosome 6.

The whole-genome array (Array 89695) shows copy number changes at a number of different loci

throughout the genome, such as on Chromosomes 1, 8, 9, 12, 15, 17, 20 and 22.