Article

A genotype calling algorithm for the Illumina BeadArray platform

Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Bioinformatics (Impact Factor: 4.62). 11/2007; 23(20):2741-6. DOI: 10.1093/bioinformatics/btm443
Source: PubMed

ABSTRACT Large-scale genotyping relies on the use of unsupervised automated calling algorithms to assign genotypes to hybridization data. A number of such calling algorithms have been recently established for the Affymetrix GeneChip genotyping technology. Here, we present a fast and accurate genotype calling algorithm for the Illumina BeadArray genotyping platforms. As the technology moves towards assaying millions of genetic polymorphisms simultaneously, there is a need for an integrated and easy-to-use software for calling genotypes.
We have introduced a model-based genotype calling algorithm which does not rely on having prior training data or require computationally intensive procedures. The algorithm can assign genotypes to hybridization data from thousands of individuals simultaneously and pools information across multiple individuals to improve the calling. The method can accommodate variations in hybridization intensities which result in dramatic shifts of the position of the genotype clouds by identifying the optimal coordinates to initialize the algorithm. By incorporating the process of perturbation analysis, we can obtain a quality metric measuring the stability of the assigned genotype calls. We show that this quality metric can be used to identify SNPs with low call rates and accuracy.
The C++ executable for the algorithm described here is available by request from the authors.

Full-text

Available from: Taane G Clark, Jan 10, 2014
0 Followers
 · 
238 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Bovine milk provides important minerals, essential for human nutrition and dairy product quality. For changing the mineral composition of the milk to improve dietary needs in human nutrition and technological properties of milk, a thorough understanding of the genetics underlying milk mineral contents is important. Therefore the aim of this study was to 1) estimate the genetic parameters for individual minerals in Danish Holstein (DH) (n = 371) and Danish Jersey (DJ) (n = 321) milk, and 2) detect genomic regions associated with mineral content in the milk using a genome-wide association study (GWAS) approach. Results For DH, high heritabilities were found for Ca (0.72), Zn (0.49), and P (0.46), while for DJ, high heritabilities were found for Ca (0.63), Zn (0.57), and Mg (0.57). Furthermore, intermediate heritabilities were found for Cu in DH, and for K, Na, P and Se in the DJ. The GWAS revealed a total of 649 significant SNP markers detected for Ca (24), Cu (90), Fe (111), Mn (3), Na (1), P (4), Se (12) and Zn (404) in DH, while for DJ, a total of 787 significant SNP markers were detected for Ca (44), Fe (43), K (498), Na (4), Mg (1), P (94) and Zn (3). Comparing the list of significant markers between DH and DJ revealed that the SNP ARS-BFGL-NGS-4939 was common in both breeds for Zn. This SNP marker is closely linked to the DGAT1 gene. Even though we found significant SNP markers on BTA14 in both DH and DJ for Ca, and Fe these significant SNPs did not overlap. Conclusion The results show that Ca, Zn, P and Mg show high heritabilities. In combination with the GWAS results this opens up possibilities to select for specific minerals in bovine milk. Electronic supplementary material The online version of this article (doi:10.1186/s12863-015-0209-9) contains supplementary material, which is available to authorized users.
    BMC Genetics 05/2015; 16(1). DOI:10.1186/s12863-015-0209-9 · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Delineating the genetic causes of developmental disorders is an area of active investigation. Mosaic structural abnormalities, defined as copy number or loss of heterozygosity events that are large and present in only a subset of cells, have been detected in 0.2-1.0% of children ascertained for clinical genetic testing. However, the frequency among healthy children in the community is not well characterized, which, if known, could inform better interpretation of the pathogenic burden of this mutational category in children with developmental disorders. In a case-control analysis, we compared the rate of large-scale mosaicism between 1303 children with developmental disorders and 5094 children lacking developmental disorders, using an analytical pipeline we developed, and identified a substantial enrichment in cases (odds ratio = 39.4, P-value 1.073e - 6). A meta-analysis that included frequency estimates among an additional 7000 children with congenital diseases yielded an even stronger statistical enr
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We investigated complex genomic rearrangements (CGRs) consisting of triplication copy-number variants (CNVs) that were accompanied by extended regions of copy-number-neutral absence of heterozygosity (AOH) in subjects with multiple congenital abnormalities. Molecular analyses provided observational evidence that in humans, post-zygotically generated CGRs can lead to regional uniparental disomy (UPD) due to template switches between homologs versus sister chromatids by using microhomology to prime DNA replication-a prediction of the replicative repair model, MMBIR. Our findings suggest that replication-based mechanisms might underlie the formation of diverse types of genomic alterations (CGRs and AOH) implicated in constitutional disorders. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 03/2015; 96(4). DOI:10.1016/j.ajhg.2015.01.021 · 10.99 Impact Factor