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dc.contributor.authorLybæk, Helle
dc.contributor.authorRobson, Michael
dc.contributor.authorde Leeuw, Nicole
dc.contributor.authorHehir-Kwa, Jayne Y.
dc.contributor.authorJeffries, Aaron
dc.contributor.authorHaukanes, Bjørn Ivar
dc.contributor.authorBerland, Siren
dc.contributor.authorde Bruijn, Diederik
dc.contributor.authorMundlos, Stefan
dc.contributor.authorSpielmann, Malte
dc.contributor.authorHouge, Gunnar Douzgos
dc.description.abstractLRFN5 is a regulator of synaptic development and the only gene in a 5.4 Mb mammalian-specific conserved topologically associating domain (TAD); the LRFN5 locus. An association between locus structural changes and developmental delay (DD) and/or autism was suggested by several cases in DECIPHER and own records. More significantly, we found that maternal inheritance of a specific LRFN5 locus haplotype segregated with an identical type of autism in distantly related males. This autism-susceptibility haplotype had a specific TAD pattern. We also found a male/female quantitative difference in the amount histone-3-lysine-9-associated chromatin around the LRFN5 gene itself (p < 0.01), possibly related to the male-restricted autism susceptibility. To better understand locus behavior, the prevalence of a 60 kb deletion polymorphism was investigated. Surprisingly, in three cohorts of individuals with DD (n = 8757), the number of deletion heterozygotes was 20%–26% lower than expected from Hardy–Weinberg equilibrium. This suggests allelic interaction, also because the conversions from heterozygosity to wild-type or deletion homozygosity were of equal magnitudes. Remarkably, in a control group of medical students (n = 1416), such conversions were three times more common (p = 0.00001), suggesting a regulatory role of this allelic interaction. Taken together, LRFN5 regulation appears unusually complex, and LRFN5 dysregulation could be an epigenetic cause of autism.en_US
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.titleLRFN5 locus structure is associated with autism and influenced by the sex of the individual and locus conversionsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2022 the authorsen_US
dc.source.journalAutism Researchen_US
dc.identifier.citationAutism Research. 2022, 15 (3), 421-433.en_US

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Navngivelse-Ikkekommersiell 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse-Ikkekommersiell 4.0 Internasjonal