/home/eoidevc6/lev-isha.eoidev8.co.il/wp-content/plugins/tracking-code-manager/includes{"id":19989,"date":"2019-04-10T09:18:25","date_gmt":"2019-04-10T09:18:25","guid":{"rendered":"https:\/\/www.lev-isha.org\/?p=19989"},"modified":"2019-04-15T06:20:09","modified_gmt":"2019-04-15T06:20:09","slug":"bicuspid-aortic-valve-identification-of-a-new-genetic-pathway","status":"publish","type":"post","link":"https:\/\/lev-isha.eoidev8.co.il\/en\/bicuspid-aortic-valve-identification-of-a-new-genetic-pathway\/","title":{"rendered":"Bicuspid Aortic Valve: Identification of a New Genetic Pathway"},"content":{"rendered":"
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Dr. Idit Gabai<\/figcaption><\/figure>\n

Bicuspid aortic valve is the most common congenital heart malformation, with an incidence in the population of 1%. It is associated with significant cardiac complications that often necessitate surgical repair.<\/p>\n

Researchers from the Cardiology Division recently identified a cohort of 28 families (70 affected individuals) with this abnormality, and used their genetic information to \u00a0identify a new genetic pathway that leads to developmental abnormalities of the heart.<\/p>\n

Dr. Idit Gabai worked on this project as for her senior medical thesis, with Dr. Ronen Durst and Professor Dan Gilon.\u00a0 This was a multi-step complex genetic study using\u00a0 tools from familial genetics and pioneering new approaches in genetic data analysis.<\/p>\n

The first step was exome sequencing of 28 family pedigrees, including 70 individuals from Israel and France.\u00a0 This type of sequencing isolates the active portions of the DNA and sequences them, making the process more efficient and more economical.\u00a0 They then isolated the mutations that were consistent in all the families.\u00a0 The team then made sure that none of the mutations that they identified had already been reported as disease-causing mutations.<\/p>\n

They then used a unique strategy for genetic analysis, using available genetic \u201cbig data\u201d to identify potential disease-causing mutations, using \u00a02 key steps:<\/p>\n

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First, they excluded all the mutations that \u00a0are common in the population\u2013 keeping only rare variants with frequency of less than 1 in 1000 in the general population.\u00a0 They then analyzed each of the remaining mutations to identify those variants that are predicted to adversely affect the function of the protein generated by the gene.<\/p>\n

In the second step, they cross-referenced the resultant genes with genes that are known to be involved in cardiac development in humans and\/or mice.<\/p>\n

The analysis process yielded 7 final candidate genes, and of these genes, the most promising candidate was MINDBOMB1 (MIB1.) \u00a0This gene is involved in a pathway that is highly active during cardiovascular development, and it is involved in nuclear signaling and gene transcription.<\/p>\n

In the cohort, they found 6 \u00a0different variants in the MIB1 gene, three nonsense and three missense \u00a0mutations<\/p>\n

The team then evaluated the pathogenicity of these mutations using several \u00a0methods:<\/p>\n