The genotyping services offered by the Genomics Core include the Illumina BeadArray technology for SNPs, and the ABI technology for resolution of fluorescently tagged PCR products encompassing STRPs or any genomic region. We find increasing number of requests for all these categories by a large number of investigators. This year, there were over 150 requests by 16 investigators from six different branches (CGB, GDRB, GMBB, GTB, IDRB and MGB). This is nearly a 50% increase compared to the previous year (108 requests). The Core processed 6400 DNA samples, nearly nine times as many as in FY2010 (730 samples), and generated over 990M genotypes. The majority of genotypes were from human genome SNP genotyping, and a wide range of high-density SNP chips (370K, 550K, 610K, 1M. 2.5M, OmniExpress, Methyl27K) were processed. The 370K, 550K, 610K, 1M and Methyl27K SNP chips are being phased out, and more than half (29 out of 46) of the requests in FY2011 were for the 2.5M and the 700K OmniExpress chips. The Core continues to provide STRP based genotyping, and received a similar number of requests as those for SNP genotyping (46 each). As expected, the STRP genotyping were typically for smaller number of samples. ABI technology is capable of separating fluorescently labeled PCR products at a single-base resolution, and in FY 2010 we adopted this capability to help one lab with developing an efficient screening strategy for their mutagenesis effort in zebrafish. This strategy helps find germline transmitting founder fish and determine the size of the insertion or deletion mutation generated by the zinc‐finger nuclease (ZFNs) technology, and in FY2011, a third of the genotyping requests the Core received were for this screening. These genotypes covered a variety of routine applications, such as linkage, association, scanning focus regions for fine mapping of linked loci, copy number variation, identification of deletion intervals, parent of origin of deletions, and speed congenics. However, we find this year the genotyping services were used for a variety of novel genome-wide studies including exploring methylation/expression in cancer, variations introduced by the iPS technology, mosaicism, uniparental disomy, homozygosity mapping and nonclassical linkage analysis, among others. While genotyping was the main activity of the Core, limited physical mapping and sequencing services, as well as access to DNA panels were also offered. Investigators continue to request aliquots of DNA panels;six requests for DNA panels were processed this year, same number as last year. However, requests for BAC clones nearly doubled, and there were 17 different requests for clones from human, mouse or zebrafish libraries. Sequencing services are limited to running the investigator provided reaction plates, and the Core received 12 requests, and ran a total of 35 plates, more than twice as many as last year. Efficient and detailed analysis of data is a daunting task, particularly for small-scale occasional users of the genotyping technology. The core offers help with the GenomeStudio application from Illumina, and now subscribes for the Nexus software for exploring copy number changes. The core is helping investigators with the analysis of the SNP data using Nexus, pennCNV, and GenomeStudio. The Core has purchased and installed an Illumina iScan that allowed genotyping with higher density (2.5M) and the high throughput (OmniExpress) SNP chips. Recently, Illumina released the Omni2.5S that complements the earlier 2.5M SNP chip to cover a total of 5M SNPs, and also a new 5M SNP chip. The core is preparing for processing these newer chips, and the higher density chips will allow running moderately large-scale genotyping services in a timely manner.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICHG200346-04
Application #
8350169
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2011
Total Cost
$504,110
Indirect Cost
Name
National Human Genome Research Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Mirabello, Lisa; Khincha, Payal P; Ellis, Steven R et al. (2017) Novel and known ribosomal causes of Diamond-Blackfan anaemia identified through comprehensive genomic characterisation. J Med Genet 54:417-425
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Mendonca, Leonardo O; Malle, Louise; Donovan, Frank X et al. (2017) Deficiency of Interleukin-1 Receptor Antagonist (DIRA): Report of the First Indian Patient and a Novel Deletion Affecting IL1RN. J Clin Immunol 37:445-451
Donovan, Frank X; Kimble, Danielle C; Kim, Yonghwan et al. (2016) Paternal or Maternal Uniparental Disomy of Chromosome 16 Resulting in Homozygosity of a Mutant Allele Causes Fanconi Anemia. Hum Mutat 37:465-8

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