1. The genetic bases BY Casey Jaroche
Diabetes
The genetic bases BY
Casey Jaroche

2. Stats and Facts
7.8% of people in the US have diabetes (23.6 million people)
7th leading cause of death in US 2006 was diabetes
Estimated diabetes costs in the US in 2007 was $174 billion
1.6 million new cases of diabetes diagnosed in 2007
Center for Disease Control and Prevention (2007)

3. Key Terms HLA -Human Leucocyte Antigen
NIMA -Non-Inherited Maternal Antigen
T1D -Type 1 Diabetes
T2D -Type 2 Diabetes
MHC -Major Histocompatibility Complex
T-cells -antigen and immune cells
IDDM -Insulin Dependent Diabetes Mellitus
INS -The Insulin Gene
MODY -Maturity Onset Diabetes in the Young
VNTR -Variable Number Tandem Repeats
DR an HLA haplotype, frequently associated with autoimmune diseases
DR an HLA haplotype, frequently associated with autoimmune diseases

5. Diagrams of T1D and T2D

6. Differences between T1D and T2D
Type One Diabetes T1D
Type Two Diabetes T2D
The body’s immune system destroys pancreatic beta cells.
Cells do not use insulin properly
Patients need insulin delivered by injection or pump
Patients need a controlled diet, regular exercise, medication
5-10% of diagnosed cases
90-95% of diagnosed cases
Risk factors: genetic, age, obesity, race/ ethnicity
Risk factors: genetic, autoimmune, environmental
Rich, 2009

7. Background of Type 1 Diabetes
Autoimmune disorder
Inherited risk
Environmental factors
18 regions of the genome are linked with diabetes risk
Horenstein, 2004

8. Diabetes Susceptibility Loci
Dean, 2004

9. IDDM1 Contains the HLA Genes
HLA genes encode MHC proteins found on the surface of cells
They help the immune system distinguish between its own cells and bad cells
HLA genes are found on chromosome 6 within the IDDM1 region
Two classes of MHC proteins; antigens and immune cells (T cells)
In healthy bodies T cells bind to chains from infectious organisms
Diabetes occurs when HLA genes tell the T cells to bind to body’s healthy cells
The diabetes linked HLA genes are call DR3 and DR4
DR3 and DR 4 are found in 95% of people with T1D
Dean, 2004

10. IDDM2 Contains the Insulin Gene
Mutation of INS causes a rare form of diabetes
INS is the only gene that produces insulin
VNTR is a variable number tandem repeat
3 classes of VNTR
Class I has repeats
Class II has around 80 repeats
Class III has repeats
Class I is associated with a high risk for diabetes
Class III is associated with protection against diabetes
VNTR affects the transcription of the insulin gene
Dean, 2004

11. 2008 Study of HLA affect on risk for T1D
Hypothesis: HLA that is not inherited from the mother, affects the risk for T1D
Studied the genes of 849 children from Sweden
563 with T1D and 286 non-diabetic children
DR3 and DR4 are risk haplotypes when inherited from either parents.
The genetic disposition is primarily conferred by HLA on human chromosome 6
Findings: “We detected a highly significant increase in T1D positively associated NIMA among healthy individuals compared with T1D patients.”
When DR3 and DR4 are present as NIMA there is a reduced risk for T1D
NIMA positively associated to T1D might provide protection from T1D.
Results indicate that a person is less likely to develop T1D if the NIMA is positively associated with T1D.
Akesson, 2009

12. Technology
Due to the variety of risk factors diabetes is very hard to predict and prevent
Future technology:
Diabetes risk profile
Cell therapy
Use of cord blood
Therapeutic drugs
Clinical Islet Transplantation
Each case of diabetes could be treated individually
Cord blood used to regenerate immune cells
Transplants islet cells from a donors pancreas to a T1D patient
DRI, 2010

13. References
Akesson K, Carlsson A, Ivarsson S, Johansson C, Weidby M, Ludvigsson J, Gustavsson B, Lernmark A, Kockum I The non-inherited maternal HLA haplotype affects the risk for type 1 diabetes. International Journal of Immunogenetics 36 (1): 1-8.
Centers for Disease Control and Prevention National diabetes fact sheet: general information and national estimates on diabetes in the United States. Atlanta, GA: U.S. Department of Health and Human Services.
Dean L, McEntyre J The genetic landscape of diabetes. Beck B, editor. England: NCBI.
Horenstein R, Shuldiner A Genetics of diabetes. Kluwer Academic Publishers. Netherlands: Reviews in Endocrine and Metabolic Disorders 5:
Rich S, Gumuscu S, Concannon P Recent progress in the genetics of diabetes. Hormone Research 71 (1):17-23.
Diabetes Research Institute Florida. [Cited 2010 April 23]. Available from: