Multifactorial Inheritance Flashcards
Identify and describe the characteristics of diseases and other traits that demonstrate multifactorial inheritance.
Multifactorial inheritance is indicated when there is an increased risk to relatives, but there is no consistent pattern of inheritance within families. In this case, it is reasonable to assume multiple genes and environmental factors contribute to disease susceptibility. The genes that contribute to multifactorial disease susceptibility may or may not include the genes that cause the disease in patients showing Mendelian inheritance. To add to the complexity, the same disease may be the outcome of different multifactorial pathways.
What are the 3 main experimental strategies used to determine the relative importance of genetic vs. non-genetic factors in contributing to the variation in a complex trait?
Experiments with twins, adoptions, immigration studies.
What is the rationale for finding disease genes?
Genes may provide clues to pathogenic mechanisms, enable new approaches to treatment, enable gene therapy, lead to inference of environmental risk factorsBoth genes and environmental factors play major roles in virtually all diseasesDisease gene discovery may highlight pathogenic mechanisms and pathways, offering new drug targets, and help facilitate disease prevention
What are the three most commonly used types of DNA polymorphisms?
MicrosatellitesSingle Nucleotide Polymorphisms (SNPs)Copy Number Variations (CNVs)
Please describe microsatelites.
They are most commonly used in forensics. Repeating sequences of 1-6 base pairs.
Please describe SNPs.
Single base changes that you can score, anywhere in the geome. Allele frequencies differ in different ethnic groups and populations. Can result in AA changes, but not always.
What are copy number variations?
Common genomic deletions, hundreds to tens of thousands of nucleotides in size. Allele frequencies differs in different ethnic groups and populations. Individually, they are rare, but collectively these are common. Can be inside or outside of genes, and can include genes. We are uncertain how often these are causal for human disease
What statistical approaches are used to test genetic linkage and association?
Simple statistics (Chi square, fischer), multiple testing correction.Note: Real association does not imply causation.
Be aware of the emerging use of genome/exome sequencing to discover disease genes and, in the future, genetic testing.
So noted.
How do twin experiments work in determining multifactorial inheritance?
If mono or dizygotic twins are raised in the same environment, but there is still a difference in concordance rate between mono and dizygotic twins, then the differences are attributed to genetics.
What if the monozygotic twins are raised apart (in different environments)?
Similarities in trait can be attributed to genetic factors.
How do adoption studies work?Biological siblings raised apart?
If adopted siblings share traits, then it is a product of their environment.Similarities are products of genes.
What are the potential difficulties in quantifying the role of genetic factors to risk of disease at the population and individual levels?
Incomplete penetrance, variable expressivity, heterogeneity, and presence of phenocopies.
What is incomplete penetrance?
Some people with a given genotype do not express the trait.
What is variable expressivity?
Individuals with the same variant do not show precisely the same disease of quantitative phenotype characteristics.
