Mapping mendelian diseases Flashcards
What is the mendelian/monogenic classification of genetic disease?
When a disease is caused by a single gene, with little or no impact from the environment
What is the Non-mendelian/polygenic classification of genetic disease?
When diseases or traits are caused by the impact of many different genes, each having only a small individual impact on the final condition
What is the multifactorial classification of genetic disease?
When diseases or traits result from an interaction between multiple genes and often multiple environmental factors
Ways to identify genes by gene mapping
- Homozygosity mapping
- Linkage analysis
- GWAS
How do we find disease-causing mutations?
By sequencing
How do we prove the disease causing mutations is causing the disease?
-Using in silico, in vitro and in vivo tools
What is genetic linkage?
-Genetic linkage is the tendency for alleles at neighbouring loci to segregate together at meiosis therefore to be linked, two loci must lie very close
What does a haplotype define?
A haplotype defines multiple alleles at linked loci
What are more likely to experience a cross over?
Crossovers more likely to occur between loci separated by some distance than those close together
What do haplotypes mark?
Haplotypes mark chromosomal segments which can be tracked through pedigrees and populations
What is the method for linkage analysis?
- First take a pedigree
- Then we use some kind of tool to generate genotyping data for your pedigree
- Then we get our data of physical and genetic distribution of markers on a genotyping array
- Afterwards we run a linkage programme
- Then we run the test in a non-parametric or parametric way
What is imposed in non-parametric and parametric testing?
- No rules imposed in non-parametric testing
- Parametric testing imposes rules about inheritance and disease frequency
What are LOD scores >3.0 taken as?
LOD scores >3.0 are taken as significant evidence for linkage
How do we find disease causing mutation?
Traditional sanger sequencing -Candidate genes Next generation sequencing -Whole genome sequencing -Whole exome sequencing
