Genetic causes and modifiers of autism spectrum disorder. Golzio c, willer j, talkowski me, oh ec, taniguchi y, jacquemont s, et al. The immune signaling adaptor lat contributes to the. Kctd is a major driver for the neurodevelopmental phenotypes associated with the. The aims of the present study were to explore the role of kctd in the development of scz and to provide a more complete picture of the allelic architecture at this risk locus. Dozens of publications suggest that kctd proteins have. Genome engineering of isogenic human es cells to model autism disorders. Substratespecific adapter of a bcr btbcul3rbx1 e3 ubiquitinprotein ligase complex required for synaptic transmission pubmed. The family of potassium channel tetramerizationdomain kctd proteins consists of 26 members with mostly unknown functions. Kctd10 is critical for heart and blood vessel development. Pdf kctd is a major driver of mirrored neuroanatomical. The function of kctd in the mammalian brain, however, remains unknown. Kctd is a major driver of mirrored neuroanatomical phenotypes of the 16p11. The minimum and the shoulder exhibited by the kctd btb domain are at slightly shorter wavelength when compared to those shown by kctd1 btb fig.
But it suggests that this one gene is the major driver. Kctd deletion reduces synaptic transmission via increased. Kctd is a major driver of mirrored neuroanatomical. We have shown previously that reciprocal under and overexpression of kctd induces macro and microcephaly with concomitant defects in neurogenesis and bilateral symmetry of postmitotic neurons. Kctd potassium channel tetramerization domain containing is a protein coding gene. Overexpression of all 29 human transcripts of a region of the 16p11. Using genetically modified zebrafish, golzio and colleagues identified kctd within 16p11. The bcr kctd e3 ubiquitin ligase complex mediates the ubiquitination of rhoa, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and promoting synaptic transmission pubmed. Here we delete the kctd gene in mice and demonstrate reduced. Genome engineering of isogenic human es cells to model. Kctd is a major driver of mirrored neuroanatomical phenotypes associated with the 16p11. May 16, 2012 read kctd is a major driver of mirrored neuroanatomical phenotypes of the 16p11. The bcrkctd e3 ubiquitin ligase complex mediates the ubiquitination of rhoa, leading to its degradation by the proteasome pubmed.
A new gene family involved in neurodevelopmental and. Research in the atsushi kamiya laboratory at johns hopkins. The aims of the present study were to explore the role of kctd in the development of scz and to provide a more complete picture of the allelic architecture at. Using the yeast 2hybrid method to screen a human hepatocyte cdna library with the small subunit of dna polymerase delta pold2. The function of kctd in mammalian brain, however, remains unknown. The subcellular localization of the uncharacterized human. A role for kctd dosage changes is consistent with autism in both a recently reported family with a reduced 16p11. Kctd10 is critical for heart and blood vessel development of. Haley speed dec insight data science fellow insight data.
The cd spectra of the newly expressed domains, kctd1 btb and kctd btb fig. May 17, 2012 kctd is a major driver of mirrored neuroanatomical phenotypes associated with the 16p11. Leveraging biobankscale rare and common variant analyses. Among its related pathways are sweet taste signaling and neuropathic painsignaling in dorsal horn neurons. These results suggest that kctd may recruit rhoa for modulating its turnover via the cullin.
Golzio c1, willer j, talkowski me, oh ec, taniguchi y, jacquemont s, reymond a, sun m, sawa a, gusella jf, kamiya a, beckmann js, katsanis n. Kctd and tnfaip1 are also related to the nervous system diseases. Pdf identification of rare variants in kctd at the. Leveraging biobankscale rare and common variant analyses to identify asphd1 as the main driver of reproductive traits in the 16p11.
Our data suggest that kctd is a major driver for the neurodevelopmental phenotypes associated with the 16p11. Our data suggest that kctd is a major driver for the neurodevelopmental phenotypes associated with the. Complete information for kctd gene protein coding, potassium. We used this approach to demonstrate that the major driver of the 16p11. The function of kctd in the mammalian brain, however, remains. To test directly whether the transcriptional dysregulation of cilia genes might be a driver of the pathology, we turned to zebrafish. A potential contributory role for ciliary dysfunction in the. Gene ontology go annotations related to this gene include identical protein binding and protein domain. Sep 24, 2019 kctd is a major driver of mirrored neuroanatomical phenotypes of the 16p11.
Diseases associated with kctd include osteoarthritis and hepatocellular carcinoma. Haley speed dec insight data science fellow insight. The bcrkctd e3 ubiquitin ligase complex mediates the ubiquitination of rhoa, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and promoting synaptic transmission pubmed. A potential contributory role for ciliary dysfunction in. Of the many genes in this locus, kctd has been implicated as a major driver of neuroanatomical and neurodevelopmental phenotypes. Kctd btbpoz domaincontaining adapter for cul3mediated. Genome engineering of isogenic human es cells to model autism disorders refugio a. Publications oh lab of neurogenetics and precision medicine. May 16, 2012 kctd is a major driver of mirrored neuroanatomical phenotypes of the 16p11. Nov 24, 20 golzio c, willer j, talkowski me, oh ec, taniguchi y, jacquemont s, reymond a, sun m, sawa a, gusella jf, et al. Genome engineering of isogenic human es cells to model autism.
The aims of the present study were to explore the role of kctd in. The bcrkctd e3 ubiquitin ligase complex mediates the ubiquitination of rhoa, leading to its degradation by the proteasome. This study does not exclude the possibility that there are other genes in the human region of 16p11. The name of the protein family is due to the sequence similarity between the conserved nterminal region of kctd proteins and the tetramerization domain in some voltagegated potassium channels. Here we delete kctd in mice and demonstrate reduced synaptic transmission. The bcr kctd e3 ubiquitin ligase complex mediates the ubiquitination of rhoa, leading to its degradation by the proteasome pubmed. May 16, 2012 our data suggest that kctd is a major driver for the neurodevelopmental phenotypes associated with the 16p11.
609 801 1046 1548 676 651 54 1323 1420 1422 1043 213 708 1193 1502 1385 718 1015 994 936 1529 30 1152 167 83 178 281 1278 1516 1218 787 616 437 599 1438 886 595 914 1355 1115