Mapping Mendelian Disease Flashcards
What is the definition of Mendelian disease?
→ A disease caused by a single gene with little or no impact from the environment
What is an example of mendelian disease?
→ PKD
What is the definition of non mendelian disease?
→ Diseases or traits caused by the impact of many different genes each having only a small individual impact on the final condition
What is an example of a non mendelian disease?
→ Psoriasis
What is the definition of a multifactorial disease?
→ Diseases or traits resulting from an interaction between multiple genes and often multiple environmental factors
What is an example of a multifactorial disease?
→ heart disease
What are the 3 ways of identifying a gene by mapping?
→ Homozygosity mapping
→ Linkage analysis
→ GWAS
How do you find disease causing mutations?
→ Sequencing
How do you prove genes cause disease?
→ In silico, in vitro and in vivo tools
What is genetic linkage?
→ The tendency for alleles at neighbouring loci to be segregated together at meiosis
When are crossovers more likely to occur?
→ between loci separated by some distance than those close together
If a marker and a disease locus are unlinked what does this mean?
→ The affected individuals in the family are less likely to inherit the same marker alleles
If a marker and a disease locus are linked what does this mean?
→ Affected individuals are more likely to inherit this haplotype block
What are the steps for the linkage analysis method?
1) a pedigree is taken
2) genotyping data is generated like a GWAS SNP array
3) Physical and genetic distribution of markers on genotypic array
4) a file is generated with pedigree information and genotyping data from microarray
5) linkage programme is run
What is non parametric linkage testing?
→ Not having assumptions about linkage data
What does non parametric linkage testing look for?
→ All affected regions are equal but different to unaffected regardless of inheritance pattern
→ Any LOD score above 3
What does parametric analysis look for?
→ All affected are equal but different to unaffected
→ AND genotypes follow the imposed inheritance pattern
What does a LOD score of -2 mean?
→ significant non linkage
What does a LOD score of -2 to 3 mean?
→ Inconclusive
Where is a gene likely to be located if the LOD score is ?> 3?
→ between the two markers defining the linkage peak
What are the symptoms of generalised lymphatic dysplasia?
→ Antenatal hydrops → Oedematous at birth → intestinal lymphangiectasia → peripheral lymphoedema → mild developmental delay
What kind of a disease is 4 limb lymphoedema?
→ autosomal dominant
What are the two methods of finding disease causing mutations?
→ Traditional Sanger sequencing
→ Next generation sequencing
- whole genome
- whole exome
