Identifying genes that may potentially cause or be associated with a disease state.
GWAS attempts to interrogate the entire ______ using high density ___ ________ without a priori developing an
hypothesis.
Genome
DNA microarrays
T/F: Associations made from GWAS studies, prove causation, allowing involvement of a gene with the
disease.
False: Does not prove causation
allows development of a testable hypothesis concerning the connection of a gene with a disease
T/F: The basic design of GWAS:
1. SNPs microarrays from non diseased and diseased people
2. compare the presence/absence of markers
3. fine tune the relationship of the disease with markers
4. narrow the gene location to a small region of a chromosome.
True
______ ______are sizeable regions of the genome to which little recombination has historically occurred, possibly over generations.
Haplotype Blocks
T/F: A limited set of haplotypes can define the entire haplotype block.
True
Most recombination events that are involved in forming Haplotype Blocks are produced by ________ _________.
Recombination Hotspots
What is used to reduce the number of SNPs from 10 million to ~500,000 when interrogating a genome?
Linkage disequilibrium, unexpected changes that should or should not be there
One can use SNPs within the haplotype block to find the actual _______ ________ that contributes to a response or pathology.
Genetic Information
What is a Linkage Disequilibrium Plat?
Provides direct visualization of pairwise associations of single nucleotide polymorphisms (SNPs).
measures associations between SNPs
What are some potential GWAS outcomes with identification of susceptible variants?
1. Novel biological insights for clinical advances:
Therapeutic targets, Biomarkers, and Prevention
2. Improved measures fo individual aetiological processes for Personalized medicine:
Diagnostics, Prognostics, and therapeutic optimization
_____ ______ _______ take all interacting systems that impact the development of a disease and "map" them to make the connections.
Genetic Linkage Diagrams
What are the two GWAS study requirements needed for analyzing the binding sequences from each sample?
Suitable population to study
High density DNA microarrays containing a wide range of SNP binding oligonucleotides
___ _____ ___ microarrays have multi-thousand pico-moles sized oligonucleotides fixed to a solid support that measures the binding of the probe using _________, silver or _________-labeled targets.
High Density DNA
Fluorometric
Chemiluminescent-labeled
Name the two suppliers of High Density DNA Microarrays. What are the length of oligonucleotides used by each?
Affymetrix- shorter 25-mer probes
Agilent- longer 60-mer probes
What is used to couple the oligonucleotides to the support in the fabrication of HDDM? How are the sequential nucleotides linked on?
Epoxy-silane, Amino-silane, Lysine etc.
DNA Synthesis Chemistry
What is the advantage/disadvantage of shorter probes on a HDDM?
Advantage: more accurate complimentation binding
Disadvantage: a slight mismatch will not bind
What is the advantage/disadvantage of longer probes on a HDDM?
Advantage: stronger signal, more binding, even slight mismatch will still bind
Disadvantage: non-specific binding and false positives
