Sökning: id:"swepub:oai:DiVA.org:uu-494536" >
Multi-Omic Investig...
Multi-Omic Investigations of a 17-19 Translocation Links MINK1 Disruption to Autism, Epilepsy and Osteoporosis
-
- Eisfeldt, Jesper (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
-
- Schuy, Jakob (författare)
- Karolinska Institutet,Karolinska Institute
-
- Stattin, Eva-Lena (författare)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
visa fler...
-
- Kvarnung, Malin (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
-
- Falk, Anna (författare)
- Karolinska Institutet,Karolinska Institute,Lund University,Lunds universitet,Neurala stamceller,Forskargrupper vid Lunds universitet,Neural stem cells,Lund University Research Groups
-
- Feuk, Lars (författare)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
-
- Lindstrand, Anna (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
-
visa färre...
-
(creator_code:org_t)
- 2022-08-20
- 2022
- Engelska.
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:16
- Relaterad länk:
-
https://doi.org/10.3...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
http://dx.doi.org/10... (free)
-
https://urn.kb.se/re...
-
https://doi.org/10.3...
-
https://lup.lub.lu.s...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- Balanced structural variants, such as reciprocal translocations, are sometimes hard to detect with sequencing, especially when the breakpoints are located in repetitive or insufficiently mapped regions of the genome. In such cases, long-range information is required to resolve the rearrangement, identify disrupted genes and, in symptomatic carriers, pinpoint the disease-causing mechanisms. Here, we report an individual with autism, epilepsy and osteoporosis and a de novo balanced reciprocal translocation: t(17;19) (p13;p11). The genomic DNA was analyzed by short-, linked- and long-read genome sequencing, as well as optical mapping. Transcriptional consequences were assessed by transcriptome sequencing of patient-specific neuroepithelial stem cells derived from induced pluripotent stem cells (iPSC). The translocation breakpoints were only detected by long-read sequencing, the first on 17p13, located between exon 1 and exon 2 of MINK1 (Misshapen-like kinase 1), and the second in the chromosome 19 centromere. Functional validation in induced neural cells showed that MINK1 expression was reduced by >50% in the patient's cells compared to healthy control cells. Furthermore, pathway analysis revealed an enrichment of changed neural pathways in the patient's cells. Altogether, our multi-omics experiments highlight MINK1 as a candidate monogenic disease gene and show the advantages of long-read genome sequencing in capturing centromeric translocations.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- reciprocal translocation
- MINK1
- autism
- epilepsy
- osteoporosis
- long-read genome sequencing
- transcriptome sequencing
- patient-specific neural stem cells
- Autistic Disorder/genetics
- Chromosome Mapping
- Epilepsy/genetics
- Humans
- Osteoporosis/genetics
- Protein Serine-Threonine Kinases/genetics
- Translocation, Genetic
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas