| 1. |
- Jallow, Muminatou, et al.
(författare)
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Genome-wide and fine-resolution association analysis of malaria in West Africa.
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; , s. 657-665
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 x 10(-7) to P = 4 x 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
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| 2. |
- Van Es, Michael A, et al.
(författare)
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Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders. - : Informa UK Limited. - 1466-0822 .- 1743-4483. ; 10:5-6, s. 441-447
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Tidskriftsartikel (refereegranskat)abstract
- A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS, independent replication of associations is crucial for identifying true-positive genetic risk factors for disease. The primary aim of this study was to study the association between FGGY and sporadic ALS in large, homogeneous populations from northern Europe. Genotyping experiments were performed using Illumina Beadchips, Sequenom iPLEX assays and Taqman technology on large case-control series from The Netherlands, Belgium, Sweden and Ireland (total: 1883 sporadic ALS patients and 2063 controls). No significant association between sporadic ALS and the six previously reported associated SNPs in FGGY was observed: rs6700125 (p =0.56), rs6690993 (p =0.30), rs10493256 (p =0.68), rs6587852 (p =0.64), rs1470407 (p =0.28) and rs333662 (p =0.44). Screening of the additional candidate loci did not yield significant associations either, with the lowest p-value in joint analysis for rs7772593 (p =0.14). We concluded that common genetic variation in FGGY is not associated with susceptibility to sporadic ALS in genetically homogeneous populations from northern Europe.
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| 3. |
- Price, Thomas S, et al.
(författare)
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SW-ARRAY : a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data.
- 2005
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 33:11
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Tidskriftsartikel (refereegranskat)abstract
- Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith-Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267-1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides.
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