Development and Clinical Application of Next Generation Sequencing

Start date:

  • 2014

Location of Project:

Principal Investigator:

  • Saeed Reza Ghaffari

Principal Associate Investigator:

  • Maryam Rafati

Outcomes:

  • Development of “Next Generation Sequencing” technique for the first time in Iran
  • Providing the personalized medicine services to clinicians (targeted Cancer Treatment, Pre-symptomatic Diagnosis of Preventable Lethal Disorders)
  • Pharmacogenetics
  • Identification of common genetic variants specific to Iranian population and building the first Variome: Iran Variation Database
  • Optimization of the recently developed “Preimplantation Genetic Screening” using NGS (PGS-NGS) technique which has been proposed as a promising method to increase pregnancy rate following assisted reproductive techniques (ART) as well as a new possible treatment for recurrent abortion and/or repeated implantation failure. This technique is now a clinical service provided to couples in Avicenna Fertility Clinic.
  • Showing the feasibility of “HLA Typing” using NGS which led to collaboration with a well-known national organization (Iranian Blood Transfusion Organization).
  • Identification of many novel mutations and variants through mutation detection in heterogeneous disorders like intellectual disability (more than 1000 known associated genes), visual loss (>350 genes), hearing loss (>200 genes) and etc.

 

Collaborative Centers:

 

Related Publications:

Preimplantation High Resolution HLA Sequencing Using Next Generation Sequencing.

Rafati M, Akhondi MM, Sadeghi MR, Tara SZ, Ghaffari SR.

Biol Blood Marrow Transplant. 2018 Apr 9. pii: S1083-8791(18)30158-7. doi: 10.1016/j.bbmt.2018.03.024.

A novel ACVR1 mutation detected by whole exome sequencing in a family with an unusual skeletal dysplasia.

Rafati M, Mohamadhashem F, Hoseini A, Hoseininasab F, Ghaffari SR.

Eur J Med Genet. 2016 Jun;59(6-7):330-6. doi: 10.1016/j.ejmg.2016.05.007. Epub 2016 May 13.

Prenatal Diagnosis of Tyrosinemia Type 1 Using Next Generation Sequencing.

Rafati M, Mohamadhashem F, Hoseini A, Ramandi SD, Ghaffari SR.

Fetal Pediatr Pathol. 2016;35(4):282-5. doi: 10.3109/15513815.2016.1167149. Epub 2016 Apr 19.

Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies.

Eisenberger T, Neuhaus C, Khan AO, Decker C, Preising MN, Friedburg C, Bieg A, Gliem M, Charbel Issa P, Holz FG, Baig SM, Hellenbroich Y, Galvez A, Platzer K, Wollnik B, Laddach N, Ghaffari SR, Rafati M, Botzenhart E, Tinschert S, Börger D, Bohring A, Schreml J, Körtge-Jung S, Schell-Apacik C, Bakur K, Al-Aama JY, Neuhann T, Herkenrath P, Nürnberg G, Nürnberg P, Davis JS, Gal A, Bergmann C, Lorenz B, Bolz HJ.

PLoS One. 2013 Nov 12;8(11):e78496. doi: 10.1371/journal.pone.0078496. eCollection 2013. Erratum in: PLoS One. 2014;9(11):e108840.

Familial intellectual disability in an Iranian family with a novel truncating mutation in CEP290.

Ghaffari SR, Rafati M, Ghaffari G, Morra M, Tekin M.

Clin Genet. 2014 Oct;86(4):387-90. doi: 10.1111/cge.12296. Epub 2013 Oct 31. No abstract available.

 

GenBank Submissions:

Please follow this link to access GenBank Submissions

 

Related Presentations:

  • Preimplantation genetic diagnosis and screening of aneuploidies using NGS (PGD-NGS and PGS-NGS): A 1-year report

3rd International Congress on Reproduction, ISERB 2017, Board Member of Panel Discussion on: “Preimplantation Genetic Diagnosis and Screening”, 20 May 2017

 

  • “Personalized Medicine in Clinical Practice”

1st Congress on Personalized Medicine, Tehran, Iran, 25 February 2017

 

  • Clinical Application of Next Generation Sequencing as a Diagnostic tool in Inborn Errors of Metabolism: Report on a 2-year Iran Experience and Case Discussion

100th Seminar in Clinical Genetics, “Report on a 2-year Clinical Experience of Next Generation Sequencing in the “First Iranian NGS Core Facility”: Discussion on Positive Findings in Patients with Inborn Errors of Metabolism, Tehran, Iran, 26 January  2017

  • Clinical Application of Next Generation Sequencing

“Symposium of Genetic Counseling, National Comprehensive Community Genetics Program”, 99th Seminar in Clinical Genetics, Held by Ministry of Health and Medical Education, 13 January 2017

 

  • Algorithmic Genetic Approach to Common Disabilities, Case Discussion:

Genetic Counseling and Diagnostic Approach to Developmental Delay / Intellectual Disability

Genetic Counseling and Diagnostic Approach to Hereditary Hearing Loss

Genetic Counseling and Diagnostic Approach to Hereditary Visual Loss

“Symposium of Genetic Counseling, National Comprehensive Community Genetics Program”, 99th Seminar in Clinical Genetics, Held by Ministry of Health and Medical Education, 13 January 2017

 

  • Clinical Application of Next Generation Sequencing as a diagnostic tool in Intellectual Disability and Developmental Delay: Report on a 2-year Iran Experience and Case Discussion

98th Seminar in Clinical Genetics, “Report on a 2-year Experience of Next Generation Sequencing in the “First Iranian NGS Core Facility”: Discussion on Positive Findings in Patients with Intellectual Disability/Developmental Delay, Tehran, Iran, 5 January  2017

 

  • Developments in Increasing the Pregnancy Rate of Assisted Reproductive Techniques using Preimplantation Genetic Screening using Next Generation Techniques (PGS-NGS): Iran Experience

97th Seminar in Clinical Genetics, “a 1-year report on Iran Experience: Case Discussion”, Tehran, Iran, 17 November, 2016

 

  • “Personalized Medicine in Diagnosis and Treatment of Cancer: Application of Next Generation Sequencing”

95th Seminar in Clinical Genetics, Tehran, Iran, 21 July, 2016

 

  • “A Comprehensive Genetic Approach to Premature Ovarian Insufficiency: New Opportunities with Next Generation Sequencing”

Laboratory and Clinic Conference, Avicenna Biotechnology Research Institute , Tehran, Iran, 19 June 2016

 

  • Increasing the Pregnancy Rate following ART using Preimplantation genetic diagnosis and screening of aneuploidies by NGS (PGD-NGS and PGS-NGS): A 1-year report

2nd International Congress on Reproduction (ISERB 2016), Board Member of Panel Discussion on: “The Role of Genetics and Epigenetics in increasing the Pregnancy Rate of Assisted Reproductive Techniques”, Tehran, Iran, 18-20 May 2016

  • “NGS technique: from library preparation to high throughput sequencing”

93th Seminar in Clinical Genetics, “Report on the 1-year Experience of Next Generation Sequencing in the “First Iranian NGS Core Facility”: Technical, Clinical and Research Aspects”, Tehran, Iran, 7 January  2016

 

  • “NGS: Basic and advanced data analysis”

93th Seminar in Clinical Genetics, “Report on the 1-year Experience of Next Generation Sequencing in the “First Iranian NGS Core Facility”: Technical, Clinical and Research Aspects”, Tehran, Iran, 7 January  2016

 

  • “Standard clinical report of exome/targeted sequencing based on ACMGG guideline”

93th Seminar in Clinical Genetics, “Report on the 1-year Experience of Next Generation Sequencing in the “First Iranian NGS Core Facility”: Technical, Clinical and Research Aspects”, Tehran, Iran, 7 January  2016

  • The Road from Next-generation Sequencing to Personalized Medicine: Technical Aspects

3rd Congress on Novel & Innovative Laboratory Technologies, Tehran, Iran, 6 October 2015

 

Summary of the Project:

This project and its subprojects were designed because of the high demand for “Next Generation Sequencing” in current medical genetic practice. Firstly, my team  developed and optimized technology for the first time in Iran (Jan 2015). Our NGS department is the first and still the only NGS facility working on whole exome and targeted sequencing inside Iran. Regarding the complexity of this technique (especially bioinformatic issues for data analysis) and limitations present in Iran, successful development of NGS in Iran has been a big achievement, appreciated by many national organizations with high media coverage. This experience which was completely based on our basic and technical knowledge of genetics, showed the ability of  my team to develop such a complicated technology without conventional technical supports of manufacturers.

Our work led to construction of the first Variome: Iran Variation Database through identification of common genetic variants specific to Iranian population.

Our work has provided a variety of personalized medicine services for clinicians including targeted cancer treatment, pre-symptomatic diagnosis of preventable lethal disorders, pharmacogenetics and etc.

We optimized the recently developed “Preimplantation Genetic Screening” using NGS (PGS-NGS) technique which has been proposed as a promising method to increase pregnancy rate following assisted reproductive techniques (ART) as well as a new possible treatment for recurrent abortion and/or repeated implantation failure. This technique is now a clinical service provided to couples in Avicenna Fertility Clinic.

We have shown the feasibility of “HLA Typing” using NGS in this project and this led to collaboration with a well-known national organization (Iranian Blood Transfusion Organization).

Whole exome sequencing and targeted sequencing have been carried out in many patients with variety of genetic disorders during a short time after starting NGS (1 year). We have detected many novel mutations in these families (please refer to the list of novel mutations submitted to GenBank) which led to carrier testing in at risk relatives and prevention of the recurrence of the disorder in high risk couples using prenatal or preimplantation genetic diagnosis.

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