sharing dog exome/genome variant and phenotype data in varda and lovd3 - peter taschner
TRANSCRIPT
Sharing dog exome/genome variant and phenotype data
in Varda and LOVD3Human Variome Project Meeting, Paris, June 2, 2016
Peter Taschner
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Serious health problems: inbreeding
Hereditary disorders in pedigree dog breeds
Selection reduces genetic diversity
Small genetic basis: founder effects
Exome / genome sequencing:
Selection of dogs to maintain genetic diversity and reduce carrier load
Variants in disease-causing genes: candidate genes for human disease
Dog variants: evidence for causal variants in human patients?
Why share dog data?
Dog genome
CanFam3.1
CanFam1.0
Nature 438: 803 (2005)
Genetic bottleneck: loss of variation
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5 dogs per breed
Panel 96 markers
Variation between 85 dog breeds
DNA passport dog - Healthy carrier
www.genoscoper.com
- Screening known variants
- Determine and maintain population dynamics
Extension:
DNA-profile for verification of:
- Parenthood
- Pedigree
OMIA
http://omia.angis.org.au
672 dog traits/disorders
201 causative variant known
378 disease models
OMIA: dog CLN6
c.829C>T p.(Trp277Arg)
Reference sequence?
More information in causal variant tables
Monarch database: dog CLN6
https://monarchinitiative.org/disease/OMIA:001443-9615
Dog exome capture kit design
Raw read data in SRA
No variant details providedNo dbSNP submissions
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Clinical exome sequencing
Varda
Re-analyze raw dog data
VCF variant file
Annotate using VEP
Import into Varda Import filtered set into LOVD
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Varda – dog variant frequencies
https://varda.generade.nl/aule/
DMD gene
Other tools available for dogs:
Mutalyzer:Name Checker
Position ConverterMapping database for dog and mouse
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Variant Effect Predictor Canine gene symbols follow HGNC systematics
Variants described in HGVS format
Challenges:Many predicted transcripts and gene models
LOVD uses human-oriented resourcesAdaptation/manual intervention necessary
http://databases.generade.nl/dog
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AcknowledgmentsBioinformatics, UAS Leiden
Thomas Olivier Koen van Diemen Rosa HegiOlga VethBo BlanckenburgFloyd Wittink
LUMC, Human Genetics
Ivo FokkemaMartijn Vermaat
LUMC, Sequence Analysis Support Core
Wibowo Arindrarto
University Gent
Bart Broeckx
OMIA
Frank Nicholas
Varda dog: https://varda.generade.nl/aule/
Dog LOVD: http://databases.generade.nl/dog