Complex genetic diseases

Question 1

Identify heterogeneity in complex genetic disease, explain how we can estimate the heritability of a common complex disease.

Answer 1

Heritability; can be low, high, medium

• It is the study of genetic contribution to increase the risk of a disease
• Used to distinguish between genetic and non-genetic factors
• estimates can vary based on the population, age groups, sampling varience

Question 2

Explain how genome-wide SNP association studies are designed and their contribution to our understanding of obesity and Diabetes ; identify the contribution of copy number variants to obesity; explain the implications of genetics for clinical management of obesity.

Answer 2

For common obesity;

1. Genome- wide association studies (GWAS)
2. Hypothesis free, common disease= common variant, see if disease statistically associated with SNPs (single nucleotide polymorphisms)
3. Findings: GWAS identified SNPs explain only small proportion of common obesity risk

Managment ;

1. Lifelong prevention + lifestyle measures
2. Medication
3. Bariatric (weight loss) surgery

Diabetes;

• Can be both poygenic and monogenic
• there are two types
  
  • Type 1;
    
    • can present at any age,
    • autoimmune disease
    • destoys pancreatic b-cells
    • treatment; insulin replacment
  • Type 2
    
    • starts in middle age or older
    • resistance in insulin function resulting in pancreatic exhaustion and reduced secretion
    • treatment; diet/ excersize, oral hypoglycaemic agents and insulin injections
  • monogenic; Maturity Onset Diabetes of the Young (MODY)
    
    • autosomal dominant affecting beta cell function and insulin secretion
    • treatment depends on affected gene (most common HNF-1 alpha)
  • identifying the genes will help to define and predict the genetic risk but also to produce precise medicines
  • Plygenic;
    
    • there is a genetic predespotition but the environment and lifestyle play a huge role
    • In genome wide association studies we try to find the most common mutations that lead to a disease and see if Single Nucleotide Plymorphism ( change in a particular nucleotide which is common in the population with a significant number more than 1%) is assiciated
  • GWAS in type 2 diabetes;
    
    • there are 90 loci which are associated with increased risk and most of them affect b cell function and not insulin receptor
    • Collectivly all SNP’S account for only 6% of type 2 diabetes meaning that the role of the environment is huge