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 other genomic region(s) of interest. Both technologies are widely used by a large number of NHGRI investigators. This year 18 investigators from five different branches (CGB, GDRB, GMBB, GTB, and MGB) used the Core genotyping services. Three additional investigators received other services provided by the Core (described below), totaling 21 investigators using the Core services this year. The Core received 583 service requests in FY2013, a 65% increase from last year (353 requests). Also, the Core processed 17,872 DNA samples this year, a 62% increase over last year (10,975 DNAs). Looking back over the past four years, there has been a steady increase in service requests (126, 217, 353 and 583) and in DNA samples processed (2,578, 6,611, 10,975, and 17,872). SNP assays (and the arrays) included Illumina GoldenGate for mouse genotypes (1449 SNPs). We concluded a large mouse GoldenGate genotyping project with 758 DNA samples. Illumina Infinium assays for human genotyping were carried out on a variety of SNP chips. The Core has smoothly transitioned from processing chips that were phased out (HumanImmunochip, Methylation27 and cytoSNP. HumanLinkage-24, HumanOmniQuad2.5) to newer SNP chips (HumanOmni2.5-8v1, HumanCore, HumanExome, HumanCoreExome, Methylation450K, HumanOmniExpress and HumanOmniExpressExome), and is prepared to process any type of array that is supported by the Illumina SNP technology. We generated 406,000 SNP genotypes for 280 mouse samples and 945 million SNP genotypes for 2,200 human samples. As anticipated from the use of high-density SNP arrays, nearly all the genotypes generated this year were from SNP technology, though the number of samples processed with SNP technology (2,480) accounted for less than sixth of those processed with ABI technology (15,392). ABI technology is capable of separating fluorescently labeled PCR products at single-base resolution, and continues to accommodate novel applications. For example, in FY2010 we developed an efficient screening strategy for zebrafish mutagenesis conducted at the Zebrafish Core. This strategy identified germline transmitting founder fish and determined the size of insertion/deletion mutations generated by ZFNs (zinc‐finger nucleases) and TALENs (transcription activator like effector nucleases) technologies. Screening requests (15, 57, 121 and 239) and the number of zebrafish DNA samples processed (829, 4,593, 6,552, and 14,891) increased dramatically from FY10 through FY13. This service accounts for most of the DNA samples processed with ABI technology this year (15,392), and is nearly twice as many as last year (8,673). This service includes 14 different mutagenesis projects from the Zebrafish Core. In FY2013, the number of zebrafish samples genotyped by the Core was three times as many as the human and mouse combined (14,891 vs 2,981). The ABI-based genotyping of human and mouse samples were for a variety studies, such as, deletion mapping by MLPA, microsatellite instability, mouse speed congenics, cell line and sample characterization, parent-of-origin studies, alternate splice site verification, paralogue ratios, scans of focus regions for linkage analysis and haplotype analysis. A whole genome scan for linkage analysis for hyperparathyroidism families was carried out using a 460-STRP markers panel. Another whole genome scan for a large Carpal Tunnel Syndrome family was generated. Though initial genotyping for linkage analysis was completed using a SNP array, defining the precise genomic interval required an additional focused five rounds of scanning using STRP markers. Each round involved searching regions for potential markers, designing and testing primers, generating genotypes for the family members, and evaluation of data by the statistical geneticist. This illustrates the nature of involved, rewarding and constant interaction the Core has with investigators in meeting their needs. In addition to numerous small SNP projects, the Core generated data for two large SNP projects. For UDP (Undiagnosed Disease Program), the Core processed a total of 960 DNA samples over the past four years, including 240 this year. Last year, NISC needed SNP-based sample identification to validate that their generated sequence came from the same individual. Genomics Core processed for NISC 1,104 DNA samples last year and another 1,584 DNAs this year. UDP and NISC programs now use HumanOmniExpressExome and HumanExome SNP chips respectively. Genotypes generated by the Core, in general, covered a variety of 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, speed congenics, methylation/expression in cancer, variations introduced by the iPS technology, mosaicism, uniparental disomy, homozygosity mapping, among others. While genotyping was the main activity of the Core, a limited amount of physical mapping services were completed. Requested clones were from human (71), mouse (17) and zebrafish (5) libraries, while BAC clones requested actually increased from last year (93 vs 56). We will continue to provide access to BAC libraries, DNA panels and ABI sequencers as they meet the needs of the investigators. Since FY2010, the Core has been assisting investigators with data analysis, and has access to software/tools such as GoldenHelix, Nexus, pennCNV, and GenomeStudio among others. One of the ongoing projects is SNP data analysis being collected from DNA samples in individuals affected with Fanconi anemia. Data from >250 cases have been analyzed for deletions, duplications, loss of heterozygosity, and regions portraying signs of chromosomal mosaicism. This effort has been very rewarding in understanding the disease process. In addition, the projects being assisted by the Core include, studies on Carpal Tunnel Syndrome, eye diseases Coloboma and Leber Congenital Amaurosis (LCA), and NF2 tumors. This service is of huge importance for investigators with small projects, as most users of the Core are, who do not have the required tools or expertize for analysis of large data sets.

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National Human Genome Research Institute (NHGRI)
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