Application of Genetics in Clinical Practice
Keywords:
Genes, DNA, NGS, DNA sequencing, chromosome
Abstract
Since the completion of the human genome project our understanding of the genes, and their function in various pathophysiological conditions, has advanced and revolutionized the medical field. From a simple chromosome study to complex DNA sequencing, array CHG, and Next-Generation sequencing technology has made it possible to diagnose many rare diseases which were thought of as nonexistence or difficult to diagnose. And many of these disorders can be treated if diagnosed early. The burden of genetic disorders seems to be high in India likely to be due to consanguinity practiced in many communities. The present article is a basic understanding of the field of genetics and when to suspect and, how to diagnose and manage in day-to-day clinical practice.
Conflict of Interest: None declared
Source of Support: Ms. Aadhira Nair is a junior research fellow on a research project funded by Gujarat State
Biotechnology Mission (GSBTM), Govt of Gujarat, India.
References
1. Gole LA, Bongso A. Fluorescent in-situ hybridization--some of its applications in clinical cytogenetics. Singapore Med J. 1997 Nov;38(11):497–503.
2. Kumar KR, Cowley MJ, Davis RL. Next-Generation Sequencing and Emerging Technologies. Semin Thromb Hemost. 2019 Oct;45(7):661–73.
3. Cheung SW, Bi W. Novel applications of array comparative genomic hybridization in molecular diagnostics. Expert Review of Molecular Diagnostics. 2018 Jun 3;18(6):531–42.
4. Sheth J, Shah S, Patel H, Bhavsar R, K B, Sheth F. A Study on Triplet Repeat Expansion Disorders in Western Indian Population. Hereditary Genetics: Current Research. 2015 Feb 19;4.
5. Sheth F, Rao S, Desai M, Vin J, Sheth J. Cytogenetic analysis of Down syndrome in Gujarat. Indian Pediatr. 2007 Oct;44(10):774–7.
6. Chong JX, Buckingham KJ, Jhangiani SN, Boehm C, Sobreira N, Smith JD, et al. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities. Am J Hum Genet. 2015 Aug 6;97(2):199–215.
7. Verma IC. Burden of genetic disorders in India. Indian J Pediatr. 2000 Dec;67(12):893–8.
8. Sheth J, Mistri M, Sheth F, Shah R, Bavdekar A, Godbole K, et al. Burden of lysosomal storage disorders in India: experience of 387 affected children from a single diagnostic facility. JIMD Rep. 2014; 12:51–63.
9. Mistri M, Tamhankar PM, Sheth F, Sanghavi D, Kondurkar P, Patil S, et al. Identification of Novel Mutations in HEXA Gene in Children Affected with Tay Sachs Disease from India. PLoS One [Internet]. 2012 Jun 18 [cited 2021 Jun 5];7(6). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3377590/
10. Venugopal A, Chandran M, Eruppakotte N, Kizhakkillach S, Breezevilla SC, Vellingiri B. Monogenic diseases in India. Mutat Res. 2018 Jun; 776:23–31.
11. Sheth JJ, Sheth FJ, Pandya P, Priya R, Davla S, Thakur C, et al. Beta-thalassemia mutations in western India. Indian J Pediatr. 2008 Jun;75(6):567–70.
12. Mickle JE, Cutting GR. Clinical implications of cystic fibrosis transmembrane conductance regulator mutations. Clin Chest Med. 1998 Sep;19(3):443–58, v.
13. Shastri SS, Kabra M, Kabra SK, Pandey RM, Menon PSN. Characterisation of mutations and genotype-phenotype correlation in cystic fibrosis: experience from India. J Cyst Fibros. 2008 Mar;7(2):110–5.
14. Kohli S, Saxena R, Thomas E, Singh K, Bijarnia Mahay S, Puri RD, et al. Mutation Spectrum of Dystrophinopathies in India: Implications for Therapy. Indian J Pediatr. 2020 Jul;87(7):495–504.
15. Kole R, Krieg AM. Exon skipping therapy for Duchenne muscular dystrophy. Adv Drug Deliv Rev. 2015 Jun 29; 87:104–7.
16. Al-Zaidy SA, Mendell JR. From Clinical Trials to Clinical Practice: Practical Considerations for Gene Replacement Therapy in SMA Type 1. Pediatr Neurol. 2019 Nov; 100:3–11.
17. Carr DR, Bradshaw SE. Gene therapies: the challenge of super- high-cost treatments and how to pay for them. Regen Med. 2016 Jun;11(4):381–93.
18. Platt FM, d’Azzo A, Davidson BL, Neufeld EF, Tifft CJ. Lysosomal storage diseases. Nat Rev Dis Primers. 2018 Oct 1;4(1):27.
19. Woolf LI, Adams J. The Early History of PKU. Int J Neonatal Screen [Internet]. 2020 Jul 29 [cited 2021 Jun 4];6(3). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC7570064/
20. Sheth J, Nair A. Treatment for Lysosomal Storage Disorders. Curr Pharm Des. 2020;26(40):5110–8.
21. Sheth F, Rahman M, Liehr T, Desai M, Patel B, Modi C, et al. Prenatal screening of cytogenetic anomalies - a Western Indian experience. BMC Pregnancy Childbirth. 2015 Apr 12; 15:90.
22. Sheth J, Mistri M, Sheth F, Datar C, Godbole K, Kamate M, et al. Prenatal Diagnosis of Lysosomal Storage Disorders by Enzymes Study Using Chorionic Villus and Amniotic Fluid. J Fetal Med. 2014 Mar 1;1(1):17–24.
2. Kumar KR, Cowley MJ, Davis RL. Next-Generation Sequencing and Emerging Technologies. Semin Thromb Hemost. 2019 Oct;45(7):661–73.
3. Cheung SW, Bi W. Novel applications of array comparative genomic hybridization in molecular diagnostics. Expert Review of Molecular Diagnostics. 2018 Jun 3;18(6):531–42.
4. Sheth J, Shah S, Patel H, Bhavsar R, K B, Sheth F. A Study on Triplet Repeat Expansion Disorders in Western Indian Population. Hereditary Genetics: Current Research. 2015 Feb 19;4.
5. Sheth F, Rao S, Desai M, Vin J, Sheth J. Cytogenetic analysis of Down syndrome in Gujarat. Indian Pediatr. 2007 Oct;44(10):774–7.
6. Chong JX, Buckingham KJ, Jhangiani SN, Boehm C, Sobreira N, Smith JD, et al. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities. Am J Hum Genet. 2015 Aug 6;97(2):199–215.
7. Verma IC. Burden of genetic disorders in India. Indian J Pediatr. 2000 Dec;67(12):893–8.
8. Sheth J, Mistri M, Sheth F, Shah R, Bavdekar A, Godbole K, et al. Burden of lysosomal storage disorders in India: experience of 387 affected children from a single diagnostic facility. JIMD Rep. 2014; 12:51–63.
9. Mistri M, Tamhankar PM, Sheth F, Sanghavi D, Kondurkar P, Patil S, et al. Identification of Novel Mutations in HEXA Gene in Children Affected with Tay Sachs Disease from India. PLoS One [Internet]. 2012 Jun 18 [cited 2021 Jun 5];7(6). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3377590/
10. Venugopal A, Chandran M, Eruppakotte N, Kizhakkillach S, Breezevilla SC, Vellingiri B. Monogenic diseases in India. Mutat Res. 2018 Jun; 776:23–31.
11. Sheth JJ, Sheth FJ, Pandya P, Priya R, Davla S, Thakur C, et al. Beta-thalassemia mutations in western India. Indian J Pediatr. 2008 Jun;75(6):567–70.
12. Mickle JE, Cutting GR. Clinical implications of cystic fibrosis transmembrane conductance regulator mutations. Clin Chest Med. 1998 Sep;19(3):443–58, v.
13. Shastri SS, Kabra M, Kabra SK, Pandey RM, Menon PSN. Characterisation of mutations and genotype-phenotype correlation in cystic fibrosis: experience from India. J Cyst Fibros. 2008 Mar;7(2):110–5.
14. Kohli S, Saxena R, Thomas E, Singh K, Bijarnia Mahay S, Puri RD, et al. Mutation Spectrum of Dystrophinopathies in India: Implications for Therapy. Indian J Pediatr. 2020 Jul;87(7):495–504.
15. Kole R, Krieg AM. Exon skipping therapy for Duchenne muscular dystrophy. Adv Drug Deliv Rev. 2015 Jun 29; 87:104–7.
16. Al-Zaidy SA, Mendell JR. From Clinical Trials to Clinical Practice: Practical Considerations for Gene Replacement Therapy in SMA Type 1. Pediatr Neurol. 2019 Nov; 100:3–11.
17. Carr DR, Bradshaw SE. Gene therapies: the challenge of super- high-cost treatments and how to pay for them. Regen Med. 2016 Jun;11(4):381–93.
18. Platt FM, d’Azzo A, Davidson BL, Neufeld EF, Tifft CJ. Lysosomal storage diseases. Nat Rev Dis Primers. 2018 Oct 1;4(1):27.
19. Woolf LI, Adams J. The Early History of PKU. Int J Neonatal Screen [Internet]. 2020 Jul 29 [cited 2021 Jun 4];6(3). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC7570064/
20. Sheth J, Nair A. Treatment for Lysosomal Storage Disorders. Curr Pharm Des. 2020;26(40):5110–8.
21. Sheth F, Rahman M, Liehr T, Desai M, Patel B, Modi C, et al. Prenatal screening of cytogenetic anomalies - a Western Indian experience. BMC Pregnancy Childbirth. 2015 Apr 12; 15:90.
22. Sheth J, Mistri M, Sheth F, Datar C, Godbole K, Kamate M, et al. Prenatal Diagnosis of Lysosomal Storage Disorders by Enzymes Study Using Chorionic Villus and Amniotic Fluid. J Fetal Med. 2014 Mar 1;1(1):17–24.
Published
2021-07-24
How to Cite
Dr. Jayesh Sheth, Ms. Aadhira Nair, Dr. Frenny Sheth, Dr. Harsh Sheth. (2021). Application of Genetics in Clinical Practice. The Indian Practitioner, 74(7), 33-40. Retrieved from https://articles.theindianpractitioner.com/index.php/tip/article/view/1216
Section
Clinical Practice
