{"id":667072,"date":"2026-05-13T17:01:09","date_gmt":"2026-05-13T17:01:09","guid":{"rendered":"https:\/\/www.newsbeep.com\/ca\/667072\/"},"modified":"2026-05-13T17:01:09","modified_gmt":"2026-05-13T17:01:09","slug":"toronto-study-identifies-non-coding-gene-ptchd1-as-linked-to-core-autism-social-behaviour-traits","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ca\/667072\/","title":{"rendered":"Toronto Study Identifies Non-Coding Gene PTCHD1-AS Linked to Core Autism Social Behaviour Traits"},"content":{"rendered":"

A\u00a0long\u2011overlooked\u00a0stretch of the human genome\u00a0appears to play\u00a0a distinct role in shaping the social and stereotypic repetitive\u00a0behaviours\u00a0that define autism spectrum disorder (ASD),\u00a0without affecting learning or other cognitive abilities,\u00a0according to a major new study published in\u00a0Nature<\/a>.\u00a0<\/p>\n

A research team\u00a0led by\u00a0The Hospital for Sick Children (SickKids) and the University of Toronto\u00a0has pinpointed PTCHD1-AS, a\u00a0long non-coding RNA gene on the X chromosome,\u00a0as a contributor to increased likelihood of ASD in males.\u00a0Notably,\u00a0deletions\u00a0within PTCHD1-AS influence social interaction and repetitive\u00a0behaviours, while leaving cognition unaffected.\u00a0\u00a0<\/p>\n

While there are around 100 genes and copy number variations linked to ASD, most encode proteins and are linked to a wide range of developmental outcomes. These findings help distinguish the biological mechanisms underlying autism\u2019s hallmark\u00a0behavioural\u00a0traits from those involved in other brain functions.\u00a0<\/p>\n

\u201cPTCHD1-AS\u00a0gives us a new entry point to study the biology of ASD,\u00a0sharpening our understanding of how specific biological pathways relate to key autism traits. This is essential, because no new therapeutics in clinical trials are designed to\u00a0modulate\u00a0the\u00a0main features\u00a0of ASD,\u201d\u00a0says senior author Stephen Scherer, senior scientist and chief of research at SickKids and a\u00a0professor of molecular genetics<\/a> at the University of Toronto\u2019s Temerty Faculty of Medicine.\u00a0<\/p>\n

A non-coding gene with a distinct role\u00a0<\/p>\n

Roughly one\u00a0in 50 children and youth in Canada\u00a0have ASD<\/a>. Despite the diverse ways they experience the condition,\u00a0changes in\u00a0social interaction and repetitive\u00a0behaviours are common across the spectrum.\u00a0\u00a0<\/p>\n

Long\u00a0non\u2011coding\u00a0RNAs (lncRNAs), such as\u00a0PTCHD1-AS,\u00a0regulate\u00a0how other genes become turned on and off\u00a0and until recently have been largely unexplored. Researchers targeted PTCHD1-AS\u00a0because it\u00a0sits in a region close to other protein-coding genes that together have\u00a0been linked to ASD\u00a0and\u00a0intellectual disability.\u00a0\u00a0<\/p>\n

In studying genomic data from over 9,300\u00a0individuals\u00a0in global\u00a0databases, they discovered that\u00a0dozens of\u00a0deletions\u00a0of\u00a0the X-linked\u00a0PTCHD1\u2011AS were associated with increased ASD\u00a0susceptibility\u00a0in males\u00a0(females have a backup X chromosome).\u00a0\u00a0<\/p>\n

Follow\u2011up\u00a0studies using mouse models developed by\u00a0the research team further\u00a0reinforced these findings.\u00a0Male mice lacking PTCHD1-AS\u00a0showed\u00a0changes\u00a0only\u00a0in social behaviour and increased repetitive actions\u00a0while they behaved typically in\u00a0learning,\u00a0memory\u00a0and attention\u00a0tasks.\u00a0<\/p>\n

\u201cOur findings suggest there is a different biology involved with our\u00a0PTCHD1-AS model compared to other ASD protein-coding models,\u201d says Lisa Bradley, first author and research associate in\u00a0The Centre for Applied Genomics (TCAG)\u00a0at SickKids.\u00a0\u00a0<\/p>\n

How\u00a0PTCHD1-AS\u00a0influences\u00a0brain circuitry\u00a0<\/p>\n

What was happening in the brains of these mice?\u00a0The team found that disrupting PTCHD1\u2011AS affected\u00a0\u201csynaptic plasticity,\u201d\u00a0the brain\u2019s ability to adapt\u00a0and fine-tune\u00a0signals in response to activity,\u00a0inside the\u00a0striatum,\u00a0where repetitive\u00a0behaviours\u00a0are\u00a0regulated.\u00a0\u00a0<\/p>\n

\u201cWhen we examined gene and protein expression in this area, we saw changes in genes and proteins involved in regulating synaptic plasticity as well as myelination, the process that allows electrical signals to travel faster between neurons. This gives us a molecular pattern we can use for future studies into the biological effect of this non-coding gene in the brain,\u201d adds Bradley.\u00a0<\/p>\n

They\u00a0traced these changes to reduced activity of protein kinase C in\u00a0a specific brain circuit connecting the cortex to the striatum, alongside increases\u00a0in two forms of synaptic plasticity.\u00a0<\/p>\n

\u201cThrough a multi-disciplinary approach combining human genetics, mouse models, multi-omics and electrophysiology,\u00a0we\u2019ve connected\u00a0a non-coding gene to measurable changes\u00a0in brain function,\u201d says study\u00a0co-author Graham Collingridge, senior investigator at Lunenfeld-Tanenbaum Research Institute, professor of physiology<\/a> at U of T\u2019s Temerty Faculty of Medicine and director of the Tanz Centre for Research in Neurodegenerative Diseases<\/a>.\u00a0\u00a0<\/p>\n

\u201cTogether, our research helps\u00a0clarify how\u00a0unique alterations in synaptic plasticity\u00a0relate to\u00a0the core features of\u00a0autism.\u201d\u00a0\u00a0<\/p>\n

Toward\u00a0a\u00a0more precise understanding of ASD biology\u00a0<\/p>\n

The research team notes by linking a specific gene and biological pathway to social and repetitive\u00a0behaviours, these findings may be relevant across all ASD diagnoses, regardless of clinical complexity.\u00a0<\/p>\n

Next steps for the research include deeper\u00a0investigation\u00a0of\u00a0the\u00a0molecular,\u00a0cellular\u00a0and circuit-level pathways influenced by\u00a0PTCHD1-AS to\u00a0identify\u00a0potential\u00a0targets\u00a0driving those core\u00a0features of ASD\u00a0and thereby inform\u00a0future precision therapeutics\u00a0for those who seek them.\u00a0\u00a0<\/p>\n

Scherer, who is also director of the McLaughlin Centre<\/a> at U of T,\u00a0adds: \u201cBeyond significantly advancing our understanding of\u00a0Autism as a human condition, the study shows how small changes in DNA can\u00a0influence complex human\u00a0behaviour.\u201d\u00a0<\/p>\n

\u201cIt\u2019s\u00a0amazing\u00a0to me\u00a0how much of our\u00a0disposition\u00a0is\u00a0genetically \u2018hardwired,\u2019\u00a0even in the traits that shape how we connect and interact,\u201d\u00a0he says.\u00a0<\/p>\n

The\u00a0study was funded\u00a0through support from\u00a0Autism Speaks,\u00a0Autism Science Foundation,\u00a0Canada Foundation for Innovation (CFI), Canadian Institutes of Health Research (CIHR), Genome Canada and Ontario Genomics, the Government of Ontario, Ontario Brain Institute, the Province of Ontario Neurodevelopment Disorders (POND) Network,\u00a0Simons Foundation Autism Research Initiative, University of Toronto McLaughlin Centre\u00a0and SickKids Foundation.\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"A\u00a0long\u2011overlooked\u00a0stretch of the human genome\u00a0appears to play\u00a0a distinct role in shaping the social and stereotypic repetitive\u00a0behaviours\u00a0that define autism…\n","protected":false},"author":2,"featured_media":667073,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[194291],"tags":[49,48,3302],"class_list":["post-667072","post","type-post","status-publish","format-standard","has-post-thumbnail","category-toronto","tag-ca","tag-canada","tag-toronto"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/667072","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/comments?post=667072"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/667072\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media\/667073"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media?parent=667072"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/categories?post=667072"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/tags?post=667072"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}