11. Human genetics(3) Flashcards
What is the lifetime risk of a complex disease?
66%
What is a complex disease? (3)
Multifactorial
- i. Polygenic
- ii. Environmental
Identified risk alleles suggest susceptibility – are NOT deterministic
Are familial
Examples of complex diseases:
- Obesity
- Rheumatoid arthritis
- Insulin dependent diabetes (Type I)
- Insulin independent (Type II)
- Multiple sclerosis
- Premature cardio‐vascular disease
- Epilepsy
- Peptic ulcer
- Hyperthyroidism
- Certain Cancers
Psychiatric Conditions • Alzheimer’s • Bipolar affected disorder • Depression • Tourette’s syndrome • Autism
Congenital Disorders
• Cleft lip and palate
• Neural tube defects
• Pyloric stenosis
Why are genetic components of complex disease identified?
- Early diagnosis and treatment
- Will allow lifestyle changes to lower risk
- Help understand the molecular basis to develop therapeutics
What are the Different possible architectures of complex diseases? (3)
• Small number of dominant alleles confer a large increase in risk o Parkinsons
• Common disease, common variant model (CDCV)- Many alleles confer a small increase in risk.
- Type II diabetes
• Intermediate- One major allele exerts a large effect, numerous other lower risk alleles
-Breast cancer
What are the risk allies for complex diseases?
Single nucleotide polymorphisms (SNPs)
The risk conferred by each SNP can be small
Correlation between genotype and disease phenotype can be weak
Where are SNPs found?
SNPs found in both coding and non-coding regions of genome
What is the frequency of common and rare SNPs?
- Common SNP’s MAF > 5%
* Rare SNPs MAF < 5%
How do you identify complex disease alleles (2 methods)?
Linkage analysis
• Looks for linkage between mapping markers and occurrence of diseases in families
Genome-wide association studies (GWAS)
• Search for alleles in a population that occur more frequently in disease cases then in matched controls.
What is Phenotypic variation?
The sum of genetic and environmental variation
What is Heriatbility?
The degree of variation in a phenotype within a population that is due to genetic variation
What is the equation for phenotypic variation?
Vp: Phenotypic variance = Vg: Genetic variance + Ve: Environmental variance
What is the equation for heritability?
Heritability =Vg:genetic variance / VP:Environmental variance
How can heritability be experimentally determined?
Twin studies
What is the difference between monozygotic and dizygotic twins?
Monozygotic (MZ)
• share ~100% of genes
• Shared environment
Dizygotic (DZ)
• Share ~ 50% of alleles
• Shared environment
What does the correlation study in twin studies show?
to what extent does phenotype in twin 1(X) correlate with Twin 2 (Y)
Can complex diseases show a continuous phenotype?
Yers
What can increase the number of distribution of variation in complex diseases?
An increase in the number of loci
What is the threshold hypothesis for disease susceptibility?
• Most diseases phenotypes are discontinuous
• Polygenes and environment produce
a distribution of liability
• The disease occurs when liability exceeds threshold
• Relatives of affected individuals have an increased risk
