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Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2–2q11.2

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dc.contributor.authorHenden, L.
dc.contributor.authorFreytag, S.
dc.contributor.authorAfawi, Z.
dc.contributor.authorBaldassari, S.
dc.contributor.authorBerkovic, S.
dc.contributor.authorBisulli, F.
dc.contributor.authorCanafoglia, L.
dc.contributor.authorCasari, G.
dc.contributor.authorCrompton, D.
dc.contributor.authorDepienne, C.
dc.contributor.authorGecz, J.
dc.contributor.authorGuerrini, R.
dc.contributor.authorHelbig, I.
dc.contributor.authorHirsch, E.
dc.contributor.authorKeren, B.
dc.contributor.authorKlein, K.
dc.contributor.authorLabauge, P.
dc.contributor.authorLeGuern, E.
dc.contributor.authorLicchetta, L.
dc.contributor.authorMei, D.
dc.contributor.authoret al.
dc.date.issued2016
dc.description.abstractFamilial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder characterized by adult onset, involuntary muscle jerks, cortical myoclonus and occasional seizures. FAME is genetically heterogeneous with more than 70 families reported worldwide and five potential disease loci. The efforts to identify potential causal variants have been unsuccessful in all but three families. To date, linkage analysis has been the main approach to find and narrow FAME critical regions. We propose an alternative method, pedigree free identity-by-descent (IBD) mapping, that infers regions of the genome between individuals that have been inherited from a common ancestor. IBD mapping provides an alternative to linkage analysis in the presence of allelic and locus heterogeneity by detecting clusters of individuals who share a common allele. Succeeding IBD mapping, gene prioritization based on gene co-expression analysis can be used to identify the most promising candidate genes. We performed an IBD analysis using high-density single nucleotide polymorphism (SNP) array data followed by gene prioritization on a FAME cohort of ten European families and one Australian/New Zealander family; eight of which had known disease loci. By identifying IBD regions common to multiple families, we were able to narrow the FAME2 locus to a 9.78 megabase interval within 2p11.2-q11.2. We provide additional evidence of a founder effect in four Italian families and allelic heterogeneity with at least four distinct founders responsible for FAME at the FAME2 locus. In addition, we suggest candidate disease genes using gene prioritization based on gene co-expression analysis.
dc.description.statementofresponsibilityLyndal Henden ... Jozef Gecz ... Mark Corbett ... et al.
dc.identifier.citationHuman Genetics, 2016; 135(10):1117-1125
dc.identifier.doi10.1007/s00439-016-1700-8
dc.identifier.issn0340-6717
dc.identifier.issn1432-1203
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]
dc.identifier.orcidCorbett, M. [0000-0001-9298-3072]
dc.identifier.urihttp://hdl.handle.net/2440/103603
dc.language.isoen
dc.publisherSpringer
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/628952
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1054618
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1002098
dc.rights© Springer-Verlag Berlin Heidelberg 2016
dc.source.urihttps://doi.org/10.1007/s00439-016-1700-8
dc.subjectMuscle, Smooth
dc.subjectChromosomes, Human, Pair 2
dc.subjectHumans
dc.subjectEpilepsies, Myoclonic
dc.subjectSeizures
dc.subjectChromosome Mapping
dc.subjectPedigree
dc.subjectFounder Effect
dc.subjectGenotype
dc.subjectGenetic Heterogeneity
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectFemale
dc.subjectMale
dc.subjectGenetic Linkage
dc.titleIdentity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2–2q11.2
dc.typeJournal article
pubs.publication-statusPublished

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