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SUMMARY:Identifying the genetic variants responsible for rare diseases - D
 r Ernest Turro\, Senior Research Associate at NHS Blood and Transplant
DTSTART:20160720T130000Z
DTEND:20160720T140000Z
UID:TALK66875@talks.cam.ac.uk
CONTACT:Dr Peter Willeit
DESCRIPTION:Rare diseases are phenotypically heterogeneous and can be caus
 ed by many different genetic variants or combinations thereof. A patient's
  phenotype can be coded by selecting a small set of terms from the Human P
 henotype Ontology (HPO). The HPO is a useful system for patient coding bec
 ause it can capture phenotypic abnormalities across many different organ s
 ystems with a flexible level of detail.\n\nI will describe a Bayesian meth
 od called "phenotype similarity regression" that models the association be
 tween an HPO-coded patient phenotype and genotype. This method estimates t
 he probability of an association together with an HPO-coded phenotype char
 acteristic of the disease. I will demonstrate that phenotype similarity re
 gression has the power to detect true associations in a large collection o
 f genome-sequenced and HPO-coded cases with rare diseases.\n\nMethods for 
 a priori filtering of variants based on population allele frequency\, cons
 ervation or predicted pathogenicity have very low specificity. Thus the va
 st majority of filtered variants are not pathogenic. I will present a meth
 od ("BeviMed") that models a mixture of pathogenic variants that influence
  the risk of disease and non-pathogenic variants that do not in a given ge
 nomic region under dominant and recessive modes of inheritance. This appro
 ach allows individualised weighting of variants and is powerful if good di
 sease labels can be constructed from the phenotypic data. We are exploring
  how it can be used to identify pathogenic variants in the regulatory non-
 coding part of the genome.\n\nI will close with a brief description of our
  new diagnostic platform ("ThromboGenomics")\, which we regularly update w
 ith our research findings and those of other groups in order to bring bene
 fits to patients without delay. 
LOCATION:Thomas and Dorothy Strangeways Room\, Strangeways Research Labora
 tory\, Wort’s Causeway\, Cambridge\, CB1 8RN.
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