BIOCHIPS

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BIOCHIPS for the analysis of genetic polymorphism
Engelhardt Institute of Molecular Biology of
Russian Academy of Sciences, Laboratory of
biological microchips
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Overview of Gel-based Biochip Technology

• High probe concentration due to high
  immobilization capacity
• High fluorescence signal and the possibility to
  use simple and cheap detecting system
• High level of discrimination between positive
  signals and background

Gel-based technology has been developed in EIMB
since 1989
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Biochips developed in EIMB allow to identify and
analyze

• Tuberculosis causative agent and its drug-
  resistance (49 mutations)
  certified and used in Russia
• Chromosome rearrangements in oncological diseases
  of blood certified and used in Russia
• Genetic predisposition to oncological diseases
  and individual tolerance of certain medications
  certified and used in Russia
• Genetic markers of an individual (in forensic
  studies) in the process of certification

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Leukemia-biochip to diagnoze 13 most common
chromosomal translocations in leukemia
t(1517) bcr3
Translocation 11q23, poor prognosis bone marrow
transplantation is required.
95 AML-?3, specific therapy with all-trans
retinoic acid (ATRA).About 95 recover.
501 ALL patients (24.4)
201 AML patients (36.4)
Oncological diseases the cause of 30 deaths in
Russia
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Hereditary breast cancer biochip
to diagnoze inherited point mutations in breast
cancer patients and family members
Wild type
gene mutation allele frequency
risk increase
185delAG 0.8 n 4
BRCA1
breast cancer by 50-80
300TgtG 0.2, n1
4153 delA 0.4, n2
4158AgtG 1.0, n5
185delAG
5382insC 3.3, n16
ovarian cancer by 20-60
BRCA2
6174delT 0.2, n1 695insT 0.2, n1
CHEK2
1100delC 1.7, n1
Breast cancer affects approximately 1 women in 10
and up to 10 of the cases are due to inherited
predisposition.
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Pharmagen-biochip
is designed to analyse genes of metabolyzing
enzymes
Applications
CYP1A1 (2A/1) (1) increased activity of the
enzyme, forming metabolites harmful for
DNA CYP2D6 (1/1), GSTT1 (-/-) (2) GSTM1 (-/-)
(3) absence of the enzymes neutralizing toxic
metabolites. NAT2 (S1/S3) (4) low speed of
acetylation of toxic metabolites MTHFR (C/C),
CYP2C9 (2/1) (5) low activity of the enzyme
CYP2C19 (1/1)

• Pharmacogenetic profile
• clinical testing for individual sensitivity
  to several drugs (thiopurines,varfarin,omeprazol
  and so on)

• Population-based association
• studies

(CYP1A1, CYP2D6, GSTM1, GSTT1, NAT2, MTHFR,
CYP2C9, CYP2C19, TPMT and NQO1)
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Vascular diseases
arterial hypertensia, myocardial infarction,
arterial and venous thromboses, ishemic disease.
Hemostasis Factor V MTHFR GP IIb/IIIa Factor
VII PAI-1 Fibrinogen
Genes of interest
Blood pressure Renin Angiotensin converting
enzyme Angiotensinogen Angiotensin II receptor
type I Angiotensin II receptor type I Bradikinin
receptor type II Beta adrenoreceptor type
1 Beta-adrenoreceptor type 2
Lipid metabolism Apolipoprotein-E LPL Apo-B
55 Russians die from cardiovascular diseases
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Perspectives

• neurological diseases, such as neurotrauma,
  stroke, dementia
• prenatal diagnostics
• cystic fibrosis
• immunohistocompatibility testing
• predisposition to diabetis
• predisposition to osteoporosis
• prognosis of cervical cancer.

Biochip is an effective tool analysis of SNPs and
mutations