FRIGE’s IHG AT GLANCEFRIGE’s IHG AT GLANCEISO 9001-2008

RESEARCH ORGANIZATIONRecognized By Govt. of India,

Ministry of Science and Technology

GENETIC CENTREFRIGE HOUSEAHMEDABAD-380 015

Tele: +91-79-26921414/65128444Fax: +91-79-26921415Email: jshethad1@gmail.comwww.geneticcentre.org

• 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

Activities at FRIGEActivities at FRIGE

• Cytogenetics

• Molecular cytogenetics

• Molecular Genetics

• Biochemical Genetics

• Basic research in Birth defects and Diabetes

Cytogenetic Study at FRIGECytogenetic 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 StudyArray CGH Study

arr cgh 18p11.332p11.31 (chr18:1-14,918,854)(hg 18-NCBI build36)x3There is a 14.9 Mb 18p11.32p11.31 duplication.

(47,XX,+mar.ish i(18)(pter q11.1::q11.1pter)(cep18+,subtelpter++),arr 18p11.332p11.31(227,585-14,918,854)x4

Screening for various storage disordersScreening 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.

Screening for storage disordersQualitative 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, -mannosidaseDefects in glycolipids and lipids : Hexosaminidase A & Total, Sphingomyelinase, -glucosidaseDefects in sulphatides : Arylsulphatase A, -galactocerebrosidaseGlycogen Storage Disorder : -1-4-glucosidaseGlobotriaosylceramide : -galactosidaseDefects in protein degradation : Tripeptidyl Peptidase I, Palmitoyl Protein ThioesteraseDefects in degradation of triglycerides and cholesteryls ester : Acid LipaseDefects in lysosomal transporters : Silaic acidDefects in lysosomal trafficking proteins : Niemann Pick disease C by Fillipin Stain method

Lysosomal enzyme study available at FRIGELysosomal enzyme study available at FRIGE

Burden of LSD’s in IndiaBurden of LSD’s in India

Prevalance of LSD's in western India total=1262, Abnormal=450 (35.66%), Normal=812 (64.34%)

21

1411

4

27

4

18

5

34

43

30

71

35

1

43

18 19

73

12

5

24

0

10

20

30

40

50

60

70

80

Typr of LSDs

No

. o

f p

ati

en

ts

Defects in degradation of gycolipids and

Defects in degrdation of

Defects in degradation of sulphatides

Defects in degerdarion of glycogenDefects in lysosomal transportes

Defects in lysosomal traff icking proteins

Defects in degredation of proteins

Prenatal Diagnosis for Lysosomal storage Prenatal Diagnosis for Lysosomal storage disorders disorders

[Total: 178, Normal/ Carrier: 133 (74.8%), Affected: 45 (25.2%)]

Tandom Mass Spectroscopy for NBSTandom Mass Spectroscopy for NBS

Total=126Abnormal=18 (14.29%), Normal=108 (85.71%)

Molecular Diagnosis for Storage disorders in India : Molecular Diagnosis for Storage disorders in India : Tay-sachs diseaseTay-sachs disease

p.E462V 20 %

c.1278insTATC 14 %

p. D322Y 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. PLoS ONE 7(6):e39122. Doi;10.1371/journal.pone.0039122

Molecular Diagnosis for Storage disorders in India: Molecular Diagnosis for Storage disorders in India: Sandhoff diseaseSandhoff 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)

Molecular Diagnosis for Storage disorders in India: Molecular Diagnosis for Storage disorders in India: Gaucher diseaseGaucher disease

I II III IV VIV VIIIVII IX X XI

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

IntronNovel mutationsGreen

Reported mutationsBlack

Current Diabetes Project : 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: 49Pro/Ala: 39Ala/Ala: 1

Pro/Pro: 125Pro/Ala: 21Ala/Ala: 1

Subject No

Association of Pro12Ala polymorphism & Vitamin D3 level in Hb-glycation.

BMI ≤25 kg/m2: 18 BMI ≥25 kg/m2: 25

Subject No BMI ≤25 kg/m2: 103 BMI ≥25 kg/m2: 90

Training given to biotech students (2005-13)Training given to biotech students (2005-13)

Ahmedabad

Anand

Jaipur

Mumbai

Gwalior

Banglore

Saurashtra

Chennai

Delhi

Training givenTo international Students

Iraq : 2Scotland : 1U. S. A. : 2Dubai : 1Nigeria : 2

Total=137

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.

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

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