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
→No rules imposed in NPL –inheritance pattern is not taken into consideration
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
→ Intestinal lymphangiectasia
→ Mild developmental delay
→ Oedematous at birth
→ Peripheral lymphoedema
AIMOP
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
What are the black areas on SNP arrays?
Represent gaps in the human genome sequence, primarily centromeres and teleomeres
