Genetics and genomics in clinical practice - 3 Flashcards
What is genomic variation?
Varying effects on health depending on where they occur and whether they alter the function of essential genes and/or their controlling elements
How can variation within the human genome arise?
- alterations in the sequence of bases in a specific section of DNA
- Microsatellites - tandem repeats of 2-6bp
- Minisatellites - tandem repeats of 10-60bp - can span several Kb
- larger deletions/duplications of DNA segments - may include one to many genes
- changes in the number or structure of chromosomes
What factors are important in determining the impact of variation in the genome?
depends on the type and where the change is
- some changes result in no or little effect while others cause medical conditions
What does variation in the genome lead to?
Normal human variation - eye colour
Differences in response to medications - effects of antidepressants
Influences likelihood of disease - diabetes
Directly result in a genetic condition e.g sickle cell anaemia
What is mendelian inheritance?
Caused by mutation in a single nuclear gene
Classical inheritance patterns:
- dominant/recessive
- autosomal/X-linked
What is non-mendelian inheritance?
Polygenic - vast majority of diseases
Multifactorial (common complex)
Maternal inheritance (mitochondrial)
Unsure what combination of genes leads to disease
In a group of patients with a common condition, what are the patterns of inheritance likely to be like?
A few will have the condition through mendelian inheritance but the majority will be due to multifactorial inheritance
Environmental factors are important in both
What are some examples of mendelian conditions?
Hypercholesterolaemia Marfan syndrome Cystic fibrosis Sickle cell disease Duchenne muscular dystrophy
Genetic components highlighted by pedigree pattern and recurrence risk
What are some examples of common conditions?
Coronary artery disease Diabetes mellitus Hypertension Cerebrovascular disease Breast and bowel cancer Schizophrenia some congenital anomalies
Genetic component suggested by clustering of cases in some families but no obvious inheritance pattern
What are the differences between genetic and environmental conditions?
Genetic
- rare
- genetics simple
- uni-factorial
- high recurrence rate
Environmental
- common
- genetics complex
- multifactorial
- low recurrence rate
How do you identify genetic and environmental influences?
observational studies of the incidence of diseases in different groups of people - need much larger groups of people to study
How is evidence on diseases gathered?
Familial clustering - not hereditary under these conditions
Twin studies
Adoption studies - split up siblings and place them in different environments
Population and migration studies - moving from high area of prevalence to low area at about age 16, means you end up taking on the environmental factors of the low prevalence area
Why are twin studies useful?
MZ= share all their genes and environment
DZ= share 50% of their genes and environment
Determining the incidence of a disease in twins helps delineate whether there are genetic and environmental components
Why is it useful to do large observation studies of families where they was a multifactorial condition?
Probabilities of recurrence for relatives can be calculated for general use- By observing the number of relatives with the same condition in the families
What are continuous traits and what is the basis of their inheritance?
Typically, polygenic inheritance is the basis for continuous traits which follow a normal distribution in the population
eg. blood pressure, height
Large number of genetic factors, each making a small contribution to the final phenotype
