Mapping Flashcards
Frequency of recombination is
Proportional to the physical distance apart
Phase:
On the same chromosome
Haplotype:
Order of in phase alleles along chromosome
Linkage maps created by:
Determining the relative position of genetic markers by frequency of marker separation during meiosis through generations
Human genome measure in:
cM centimorgan
1 cM = recombination fraction of 1/100 meioses
Physical equivalent to between 0.7 and 1 Mb of DNA
What is the odds of linkage?
The ratio between the likelihood of two loci begin linked at a certain distance vs the likelihood they are not linked at all
The logarithm of odds
LOD score (Z) is the standard unit o linkage
Genetic mapping of disease causing mutant genes
Identify affected family/families
Determine pattern of inheritance (pedigree)
Isolate chromosomal DNA (genomic) from each person
Carry out genetic mapping; find out which markers co-segregate with disease
Deduce approximate locus of gene
Genetic maps provide a rough idea where a disease gene is Eventually you will want to work with physical DNA by:
I you know approx. where disease gene is and now you want to clone it I.e identify it
Allows start of human genome project
Huge quantities o DNA kept in:
A library (storage/duplication/distribution) A database (relationships)
Making a DNA clone library
- Break up Han DNA into small fragments using restriction digest
- Place each fragment in a vector (cloning step) which is a DNA sequence that an replicate in a prokaryotic host
- Store in bacterial or yeast cells as clone libraries
- will form clonal populations - these can be stored, analysed or further propagated
- Can also make libraries from mRNA found in a tissue. Convert to cDNA then clone. A cDNA library representing all genes expressed
How do you turn a library into a true physical map?
Relationships
Use bacterial/yeast clones as probes for FISH…tells you where they are located and on which chromosomes
Which genetic markers do they contain?
Which ones overlap? Chromosome walking! A Contig
Ask are the alleles of the two microsatellite loci alway inherited together, mostly or 50/50 chance?
This indicates complete, partial or no linkage