1. FRIGE’s IHG AT GLANCE ISO 9001-2008 RESEARCH ORGANIZATION Recognized By Govt. of India, Ministry of Science and Technology GENETIC CENTRE FRIGE HOUSE AHMEDABAD-380 015 Tele: +91-79-26921414/65128444 Fax: +91-79-26921415 Email: jshethad1@gmail.comjshethad1@gmail.com www.geneticcentre.org

2. FRIGE’S Genetic Centre Translation Research IHG Education and Research Development

3. To carry out basic and translation research in Genetics and Endocrinology To propagate scientific temperament in the state To create HRD in Biotechnology and Genetic Science AIMS & OBJECTIVES

4. Activities at FRIGE Cytogenetics Molecular cytogenetics Molecular Genetics Biochemical Genetics Basic research in Birth defects and Diabetes

5. Cytogenetic Study at FRIGE CLINICAL DIAGNOSISTOTAL CASESNORMALABNORMAL DOWN SYNDROME78183698 RFL/BOH41683996172 PRIMARY AMENORRHOEA378265113 MISCELLANEOUS917807110 HYPOGONADISM18315033 AMBIGUOUS GENITALIA25924118 CANCER904408496 ABORTUS17041286418 PRENATAL1285119095 TOTAL1057984262153

8. Indigenous DNA Rotor

9. Array CGH Study arr cgh 18p11.332p11.31 (chr18:1-14,918,854)(hg 18-NCBI build36)x3 There is a 14.9 Mb 18p11.32p11.31 duplication. (47,XX,+mar.ish i(18)(pter  q11.1::q11.1  pter)(cep18+,subtelpter++), arr 18p11.332p11.31(227,585- 14,918,854)x4

12. Screening for various storage disorders Screening for Mucopolysaccharidosis (Urinary GAG qualitative and quantitative study from urine) Screening for I-cell disease (Plasma study with p-NCS substrate) Screening for Gaucher/NPD A or B diseases (Plasma Chitotriosidase study) Sheth J, Sheth F, Oza N, Gambhir P, Dave U, Shah R. Plasma Chitotriosidase activity in children with lysosomal storage disorders. Ind J Pediatrics.77:203-205. 2010. Sheth J, Mistri M, Kamate M, Vaja S, Sheth F: Diagnostic strategy for mucolipidosis II/III. Ind Pediatrics 49:975-977, 2012.

13. Screening for storage disorders Qualitative GAG analysis by electrophoresis for MPS screening Plasma chitotriosidase for screening of Gaucher’s disease and NPD A/B I-cell disease screening by enzyme study from plasma Lysosomal enzyme study available at FRIGE Mucopolysaccharide Panel:  -iduronidase,  -iduronidate sulphatase, Heparan sulphamidase, N-Ac-  -glucosaminidase,  -galactose-6-sulphate sulphatase,  -galactosidase, Aryl sulphatase B,  -glucuronidase, Glycoproteins Degradation:  -fucosidsase,  -mannosidase Defects in glycolipids and lipids: Hexosaminidase A & Total, Sphingomyelinase,  -glucosidase Defects in sulphatides : Arylsulphatase A,  -galactocerebrosidase Glycogen Storage Disorder:  -1-4-glucosidase Globotriaosylceramide:  -galactosidase Defects in protein degradation: Tripeptidyl Peptidase I, Palmitoyl Protein Thioesterase Defects in degradation of triglycerides and cholesteryls ester : Acid Lipase Defects in lysosomal transporters: Silaic acid Defects in lysosomal trafficking proteins: Niemann Pick disease C by Fillipin Stain method Lysosomal enzyme study available at FRIGE

14. Burden of LSD’s in India

15. Prenatal Diagnosis for Lysosomal storage disorders [Total: 178, Normal/ Carrier: 133 (74.8%), Affected: 45 (25.2%)]

16. Tandom Mass Spectroscopy for NBS Total=126 Abnormal=18 (14.29%), Normal=108 (85.71%)

17. Molecular Diagnosis for Storage disorders in India : Tay-sachs disease p.E462V20 % c.1278insTATC14 % p. D322Y11 % Mehul Mistri; Parag M Tamhankar, Frenny Sheth; Daksha Sanghavi; Pratima Kondurkar; Swapnil Patil; Susan Idicula- Thomas; Sarita Gupta; Jayesh Sheth (2012) Identification of novel mutations in HEXA gene in children affected with Tay- Sachs disease from India. PLoS ONE 7(6):e39122. Doi;10.1371/journal.pone.0039122

18. Molecular Diagnosis for Storage disorders in India: Sandhoff disease Sheth J, Mistri M, Ankleshwaria C Tamhankar P, Bavdekar A, Datar C, Kamate M, Gupta S, Mehta S, Sheth F. Molecular analysis for Gaucher, Tay-sach’s and Sandhoff disease in India Patients. 62th Annual meeting of ASHG-2012. (Abstract ID: 2803W)

19. Molecular Diagnosis for Storage disorders in India: Gaucher disease IIIIIIIVVIVVIIIVIIIXXXI L444P,R463C, I466S/? R359Q,G355D,V352M,S356F, R329C, E326K R395C R496C Sheth and Chitra et al: Unpublished work G289A L444P as predominant mutant allele in 65.6 % (21/32) India GD patients Exon 8 and 10 are the hotspot region of the GBA gene where 93.74% of mutant allele are present Exons UTR Intron Novel mutationsGreen Reported mutationsBlack

20. Current Diabetes Project : Effect Pro12Ala polymorphism and BMI on A1C level rs1801282, CCA>GCA, g.96890 C>G, c.34C>G, p.Pro12Ala Avisek Majumder, Jayesh J Sheth, Frenny Sheth et al. Effect of PPAR2 gene polymorphism (Pro12Ala) on HbA1C and its association with BMI in Type 2 diabetes subjects from Western India; Endocr Rev 2013; Vol. 34 Title: “Effect of genetic variations in PPARG2 and ADRB3 gene in type 2 diabetic(T2D) subjects of Gujarat in relation to drug response” PI: Dr. JJSheth, Co-PI- Dr. FJ Sheth, JRF: A. Majumder. Exons UTR Intron Pro/Pro: 49 Pro/Ala: 39 Ala/Ala: 1 Pro/Pro: 125 Pro/Ala: 21 Ala/Ala: 1 Subject No Association of Pro12Ala polymorphism & Vitamin D 3 level in Hb-glycation. BMI ≤25 kg/m 2 : 18 BMI ≥25 kg/m 2 : 25 Subject No BMI ≤25 kg/m 2 : 103 BMI ≥25 kg/m 2 : 90

21. Training given to biotech students (2005-13) Ahmedabad Anand Jaipur Mumbai Gwalior Banglore Saurashtra Chennai Delhi Training given To international Students Iraq : 2 Scotland: 1 U. S. A.: 2 Dubai: 1 Nigeria : 2 Total=137

22. Highlights  Identified gene mapping for ‘Clouston Syndrome’ in collaboration with Geneva University. U Radhakrishna, J Blouin, H Mehenni, T Mehta, F Sheth, J Sheth, J Solanki, S Antonarakis. (1997) The gene for Autosomal Dominant Hidrotic Ectodermal Dysplasia (Clouston Syndrome) in a large Indian family maps to the 13q11-q12.1 pericentromeric region. American Journal of Medical Genetics. 71: 80-86.  Coined the terminology of ‘Sub-biochemical Hypothyroidism in cases with normal TSH using TRH’. J Sheth, P Thakor, B Trivedi, N Shah, R Vaidya. (1999) Sub-biochemical hypothyroidism: An exaggerated TSH response to TRH. J of Asso of Physician of India. 47(3): 275-279.  Demonstrated for the first time about MTHFR (CT) allele to be commonly observed in our population & reported about the role of protein and Vitamin B12 together with folate interacting with unknown genes in folate metabolism pathway. J. Sheth, F. Sheth (2003). Gene Polymorphism and Folate metabolism: A Maternal risk factor for Down syndrome? Indian Pediatrics 40(2):115-123.  Demonstrated the role of Vitamin B12 in neural tube defects (NTD’s). J. Sheth,F. Sheth, N. Pandya, R. Vaidya (2003) Recurrent neural tube defects and Deficiency of Vitamin B12 beyond Folic Acid. The Journal of Obstetrics and Gynecology of India Nov/ Dec 2003:53 No 6 596-597. K. Godbole, P. Gayathri, S. Gule, BV Sasirekha, A. Kanitkar-Damle, N. Memane, S. Suresh, J. Sheth, GR Chandak, CS Yajnik (2011). Maternal one carbon metabolism, MTHFR and TCN2 genotypes and neural tube defects in India. Birth Defects Res A Clin Mol Teratol. 91(9): 848-56. Doi: 10.1002/bdra.20841.

23. Highlights  Developed indigenous FISH probes using BAC clones for various micro-deletion syndromes and cancer. F Vinsheth, Z Antonella, A Luisa, A Shah, J Sheth, M Rocchi (2003). Cytogenetics and Fluorescence In-Situ Hybridization in detection of haematological Malignancies. Indian Journal of Cancer. 40(4): 135-139.  Demonstrated large series of Down syndrome children from Western part of India and showed non-classical Down syndrome is higher from this region. F Sheth, S Rao, M Desai, J Vin, J Sheth (2007). Cytogenetic Analysis of Clinical suspected Down syndrome cases in Gujarat. Indian Paediatrics. 44(10): 774-777.  First Indian study on non-invasive prenatal diagnosis of Down syndrome and other aneuploidy by ‘Triple Marker Study’ and established Indian norms for the study. J Sheth, F Sheth, N Oza, M Doshi (2008). Triple maker study in mid-trimester of pregnancy and risk of chromosomal abnormality: An Indian Experience. Indian Journal of Obstetrics and Gynecology. 58(2):142-146.  Only Centre in India to carry out study for ‘Cholesterol transport disorders (NPD-C)’ and ‘Glycogen storage disorders type-III’ by debranching enzyme study. J Sheth, F Sheth, N Oza (2008). Niemann-Pick type C disease. Indian Pediatr. ;45(6):505-7.  Study of ‘Cryptic Genomic Imbalance’ in cases having MCA and intellectual disability. J Andrieux, F Sheth (2009). CGH-Array study and its utility in children for detection of Constitutional and Acquired anomalies. Indian Journal of Experimental Biology. 47: 779-791

24. Highlights  Identified novel mutation for ‘Tay-Sach disease’ in Indian children in ‘HEXA gene’. M Mistri, P Tamhankar, F Sheth, D Sanghavi, P Kondurkar, S Patil, S Thomas, S Gupta, J Sheth (2012). Identification of novel mutations in HEXA gene in children affected with Tay Sachs disease from India. PLoS ONE. 7(6): e39122. doi:10.1371/journal.pone.0039122  Developed simple colorimetric method for screening of ‘Mucolipidosis-II/ III’. J. Sheth, M. Mistri, M. Kamate, S. Vaja, F. Sheth (2012). Diagnostic Strategy of Mucolipidosis II/III. Indian Pediatrics. 49(12): 975-977.  Demonstrated burden of ‘Lysosomal Storage Disorders’ in children from India. J. Sheth, M. Mistri, F. Sheth, R. Shah, A. Bavdekar, K. Godbole, N. Nanavaty, C. Datar, M. Kamate, N. Oza, C. Ankleshwaria, S. Mehta, M. Jackson (2013). Burden of Lysosomal Storage Disorders in India: Experience of 387 Affected Children from a Single Diagnostic Facility. JIMD Reports. DOI 10.1007/8904_2013_244.  Trained more than 200 students from biotechnology