Characterization of the molecular defects of 9p deletion syndrome using CRISPR Technology
Disciplines
Life Sciences
Abstract (300 words maximum)
An individual inherits one set of chromosomes from the mother and one set from the father. 9p deletion patients inherited a faulty chromosome 9 with a missing piece of chromosomal DNA from one of parents. These patients have triangular shaped head (called trigonocephaly), severe mental disability, heart defect and autistic-like behavior. Trigonocephaly is a key feature of 9p deletion syndrome. A broader term for the distorted skull is craniosynostosis. Scientists have identified several genes which cause craniosynostosis when they are mutated. None of these genes are located on human chromosome 9, thus are unlikely the cause of the trigonocephaly seen in 9p deletion patients. The cause of the trigonocephaly in 9p deletion syndrome is unknown. Cerberus 1 (CER1) gene is a candidate gene and it is located on 9p. CER1 gene plays an important role in early embryo development. To investigate the potential role of CER1 gene in causing trigonocephaly, we used CRISPR technology to precisely remove a regulatory element near CER1 gene. CRISPR is a new and powerful tool in genome editing. CRISPR stands for clustered regularly interspaced short palindromic repeats. We used CRISPR and Cas9 to make double stranded DNA cuts in the pre-selected DNA sequences on the human chromosome 9p. In the first series of CRISPR experiments we precisely deleted the enhancer 5008 using CRISPR in a user-friendly human cell line HEK. We are currently investigating the effect of the enhancer 5008 on the CER1 gene activity in the human mesenchymal progenitor cells.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Xueya Hauge
Characterization of the molecular defects of 9p deletion syndrome using CRISPR Technology
An individual inherits one set of chromosomes from the mother and one set from the father. 9p deletion patients inherited a faulty chromosome 9 with a missing piece of chromosomal DNA from one of parents. These patients have triangular shaped head (called trigonocephaly), severe mental disability, heart defect and autistic-like behavior. Trigonocephaly is a key feature of 9p deletion syndrome. A broader term for the distorted skull is craniosynostosis. Scientists have identified several genes which cause craniosynostosis when they are mutated. None of these genes are located on human chromosome 9, thus are unlikely the cause of the trigonocephaly seen in 9p deletion patients. The cause of the trigonocephaly in 9p deletion syndrome is unknown. Cerberus 1 (CER1) gene is a candidate gene and it is located on 9p. CER1 gene plays an important role in early embryo development. To investigate the potential role of CER1 gene in causing trigonocephaly, we used CRISPR technology to precisely remove a regulatory element near CER1 gene. CRISPR is a new and powerful tool in genome editing. CRISPR stands for clustered regularly interspaced short palindromic repeats. We used CRISPR and Cas9 to make double stranded DNA cuts in the pre-selected DNA sequences on the human chromosome 9p. In the first series of CRISPR experiments we precisely deleted the enhancer 5008 using CRISPR in a user-friendly human cell line HEK. We are currently investigating the effect of the enhancer 5008 on the CER1 gene activity in the human mesenchymal progenitor cells.