2009 Vienna - European Society of Human Genetics

Genomics, Genomic technology and Epigenetics
P11.051
Allelic spectra of large genomic regions identified by DNA
pooling, array capture and high throughput sequencing
L. H. Franke 1 , K. Hunt 1 , G. Heap 1 , J. Yang 2 , N. Bockett 1 , V. Mistry 1 , C. A. Mein 3 ,
R. J. Dobson 3 , Z. Albertyn 4,5 , C. Chelala 6 , C. Hercus 5 , D. A. van Heel 1 ;
1 Institute of Cell and Molecular Science, Barts and The London School of
Medicine and Dentistry, London, United Kingdom, 2 Diabetes and Inflammation
Laboratory, Department of Medical Genetics, Cambridge Institute for Medical
Research, University of Cambridge, Addenbrooke’s Hospital, Cambridge,
United Kingdom, 3 The Genome Centre, Barts and The London School of Medicine
and Dentistry, London, United Kingdom, 4 Novocraft Technologies Sdn Bhd,
Kuala Lumpur, Malaysia, 5 Centre for Comparative Genomics, Murdoch University,
Murdoch, Australia, 6 Centre for Molecular Oncology and Imaging, Institute
of Cancer & CR-UK Clinical Centre, Barts & The London School of Medicine
(QMUL), London, United Kingdom.
Genome wide association studies (GWAS) typically report regions with
common tag variants, variably correlated with the actual biologically
causal genetic variants. Additional, independently associated, rare and
common variants may exist. To identify the spectrum of genetic variants
at three celiac disease associated genomic regions (total 1.26Mb,
of which 1.01Mb non-repeat sequence was tiled and analysed), we
made 10 pools of 8 human DNA samples and enriched each pool using
Nimblegen sequence capture microarrays and high-throughput sequenced
captured fragment paired-ends. We developed variant calling
algorithms and identified 3457 SNPs (45.8% previously known), 517
small (≤7bp) insertion-deletions variants (25% previously known) and
over 10 larger structural variants by read-pair insert analysis. A 4.98%
per-SNP false negative rate was determined using sample Hap300
BeadChip genotypes. A 6.1% per-SNP false positive rate was determined
using deep dideoxy capillary resequencing of 52 randomly
selected SNPs. These methods will advance identification of causal
variants from GWAS regions.
P11.052
Influences of genetic variants on plasma factor VIII levels in
female carriers of hemophilia A
B. Horvath 1 , F. Abu-Hamdeh 2 , R. Freitag 1 , C. Male 3 , I. Pabinger 2 , K. Thom 3 , C.
Mannhalter 1 ;
1 Department of Medical and Chemical Laboratory Diagnostics, Medical University
Vienna, Austria, 2 Department of Internal Medicine I, Division of Hematology
and Haemostaseology, Medical University Vienna, Austria, 3 University hospital
for paediatrics, Medical University Vienna, Austria.
Introduction: An inversion in intron 22 of the factor 8 gene causes severe
hemophilia A with FVIII activity (FVIII:C)