FRIGE s IHG AT GLANCE ISO 9001 -2008 RESEARCH

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: jshethad 1@gmail. com www. geneticcentre. org

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

AIMS & OBJECTIVES • 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

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

Cytogenetic Study at FRIGE CLINICAL DIAGNOSIS TOTAL CASES NORMAL ABNORMAL DOWN SYNDROME 781 83 698 RFL/BOH 4168 3996 172 PRIMARY AMENORRHOEA 378 265 113 MISCELLANEOUS 917 807 110 HYPOGONADISM 183 150 33 AMBIGUOUS GENITALIA 259 241 18 CANCER 904 408 496 ABORTUS 1704 1286 418 PRENATAL 1285 1190 95 TOTAL 10579 8426 2153

Indigenous DNA Rotor

Array CGH Study (47, XX, +mar. ish i(18)(pter q 11. 1: : q 11. 1 pter)(cep 18+, subtelpter++), arr 18 p 11. 332 p 11. 31(227, 58514, 918, 854)x 4 arr cgh 18 p 11. 332 p 11. 31 (chr 18: 1 -14, 918, 854)(hg 18 -NCBI build 36)x 3 There is a 14. 9 Mb 18 p 11. 32 p 11. 31 duplication.

si s y ph em ia tro r A cu la us ss la ro g bi n 208 Al Number of 250 Patients M ha T ib 450 D SC MD is A m (O Pa n C A 1 el Fr g ie en dr ei e) M ch yo A to ta ni c xi a D ys tro ph H Fr y em ag op ile -X hi lia S yn dr om e H H un LA tig B to 27 n D is JA ea K 2 se M N M ito SH ut ch L at on (G io dr n JB ia M 2/ l D TH C is FR on ea ne se Yq xi (L n M ei 26 ic gh ro ) , L de H le O ti N , M on ER R F) in al B- in yp 30 Sp F tic ys a 50 C si la op ot en 5 G nd r ho Ac 3 A y. P C 500 438 400 350 300 206 205 150 100 36 67 21 12 18 22 42 30 Disease Name 32 26 20 22 14 25 0

ot dr ba r M ic E usc ct od ula r er m Atro al D ph R ET ys y p T Br Ap S lasi ea o ynd a st E C G rom en an BC e R ce /A otyp r ( in BR BL g C by A 1 P C & 2 R g en e) TG CA C H M an av 1 g C e a hr on n D ne is ic C e M T 1 Pan ase cr (P M eat P 2 it Ep 2 is D ge y id er sto ne m ni SR a Y ) al B ( ge ul DY lo T 1 ne sa D ge ys ne tro ) O p st eo hic Fa pe a H ct er or tros ed V i ito L s ry Ty eid H em ros en oc ine m hr om ia U a G T 1 tos O A 1 is st eo M ge ge ne LC ne 1 si g s Im en e p PA erfe c N K 2 ta g en e ul B al in hy An Sp 14 Number of Patients 2 13 12 11 10 8 8 6 6 5 4 4 2 2 1 2 4 3 3 2 1 Rare Disease Name 2 3 2 1 1 0

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.

Lysosomal enzyme study available at FRIGE 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

Burden of LSD’s in India

Prenatal Diagnosis for Lysosomal storage disorders [Total: 178, Normal/ Carrier: 133 (74. 8%), Affected: 45 (25. 2%)]

Tandom Mass Spectroscopy for NBS Total=126 Abnormal=18 (14. 29%), Normal=108 (85. 71%)

Molecular Diagnosis for Storage disorders in India : Tay-sachs disease p. E 462 V 20 % c. 1278 ins. TATC 14 % p. D 322 Y 11 % 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. PLo. S ONE 7(6): e 39122. Doi; 10. 1371/journal. pone. 0039122

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. 62 th Annual meeting of ASHG-2012. (Abstract ID: 2803 W)

Molecular Diagnosis for Storage disorders in India: Gaucher disease UTR R 359 Q, G 355 D, V 352 M, S 356 F, R 329 C, E 326 K Exons Intron Green Novel mutations Black Reported mutations I II IV G 289 A V VI VII R 395 C VIII IX L 444 P, R 463 C, I 466 S/? X XI R 496 C • L 444 P 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 Sheth and Chitra et al: Unpublished work

Current Diabetes Project : Title: “Effect of genetic variations in PPARG 2 and ADRB 3 gene in type 2 diabetic(T 2 D) subjects of Gujarat in relation to drug response” PI: Dr. JJSheth, Co-PI- Dr. FJ Sheth, JRF: A. Majumder. UTR Exons rs 1801282, CCA>GCA, g. 96890 C>G, c. 34 C>G, p. Pro 12 Ala Intron 10 9 8 7 6 5 4 3 2 1 0 Association of Pro 12 Ala polymorphism & Vitamin D 3 level in Hb-glycation. 10 8. 1 7. 5 8. 4 ≤ 25. 0 Kg/m 2 >25. 0 Kg/m 2 Mean Hb. A 1 C % Hb. A 1 C (%) Effect Pro 12 Ala polymorphism and BMI on A 1 C level 8 6 7. 26 8. 29 4 12 Ala 2 12 Pro 0 12 Ala ≤ 25. 0 nmol/L 12 Pro BMI (Kg/m 2) Subject No 8. 35000000 8. 59 000001 BMI ≤ 25 kg/m 2: 18 BMI ≥ 25 kg/m 2: BMI ≤ 25 103 BMI ≥ 25 kg/m 2: 90 Pro/Pro: 125 Pro/Ala: 21 Ala/Ala: 1 Vitamin D 3 level (nmol/L) >25. 0 nmol/L Pro/Pro: 49 Pro/Ala: 39 Ala/Ala: 1 Avisek Majumder, Jayesh J Sheth, Frenny Sheth et al. Effect of PPAR 2 gene polymorphism (Pro 12 Ala) on Hb. A 1 C and its association with BMI in Type 2 diabetes subjects from Western India; Endocr Rev 2013; Vol. 34

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

Highlights Ø Identified gene mapping for ‘Clouston Syndrome’ in collaboration with Geneva University. U Radhakrishna, J Blouin, H Mehenni, T Mehta, F Sheth, J Solanki, S Antonarakis. (1997) The gene for Autosomal Dominant Hidrotic Ectodermal Dysplasia (Clouston Syndrome) in a large Indian family maps to the 13 q 11 -q 12. 1 pericentromeric region. American Journal of Medical Genetics. 71: 80 -86. Ø 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. Ø Demonstrated for the first time about MTHFR (CT) allele to be commonly observed in our population & reported about the role of protein and Vitamin B 12 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. Ø Demonstrated the role of Vitamin B 12 in neural tube defects (NTD’s). J. Sheth, F. Sheth, N. Pandya, R. Vaidya (2003) Recurrent neural tube defects and Deficiency of Vitamin B 12 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 TCN 2 genotypes and neural tube defects in India. Birth Defects Res A Clin Mol Teratol. 91(9): 848 -56. Doi: 10. 1002/bdra. 20841.

Highlights Ø Ø 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. Ø 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. Ø 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. Ø 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

Highlights Ø 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. PLo. S ONE. 7(6): e 39122. doi: 10. 1371/journal. pone. 0039122 Ø 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. Ø 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. Ø Trained more than 200 students from biotechnology