Term
| Quantitative Trait Loci (QTL) |
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Definition
| – the genes that control variation in quantitative (or complex traits) |
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Term
| Association mapping/Linkage-disequilibrium mapping |
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Definition
a method for identifying statistical associations between molecular markers and phenotypic variation for complex traits → linkage disequilibrium in a population between the marker locus and a functional variant in a gene can cause the association
-this allows researches to directly identify the specific genes that control the difference in phenotype among members of a population
-proves statistical evidence for association between the SNP and the trait |
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Term
| genome-wide association (GWA) study |
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Definition
-using association mapping to scan the entire genome for genes contributing to quantitative variation
Major advantage: candidate genes are not required since every gene in the genome is being scanned
-this study can only be accomplished if molecular markers over the entire genome are available
-these studies have enabled geneticists to identify hundreds of genes that contribute to the risks of developing many common diseases
-approach works if there are many people who share the same mutation (they have a common allele) |
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Term
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Definition
points in the genome where crossing over occurs at high frequency
-these hotspots disrupt linkage equilibrium
-separate haplotype blocks |
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Term
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Definition
-when close to each other, tend to be in a strong disequilibrium, those farther apart are in weak or no disequilibrium
-if they are not separated by hotspot - form a haplotype block of stringy correlated SNPs
-use for GWAS instead of micro satellites because VNTRs change too frequently, SNPs change so slowly |
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Term
| Why have GWAS studies only been able to account for a small fraction of the heritable variation? |
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Definition
hypothesis: susceptibility for many common diseases (or heigh variation) is caused by a larger number of rare alleles
-the disease-susceptiblity alleles that segregate in one family are different from those in another, unrelated family |
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Term
| Genotyping SNPs in the human genome |
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Definition
•Make short oligonucleotides and put one per line of SNP’s → SNPs vs. reference&variant → hybridize to the DNA (fragmented to small size and labeled with a fluorescent dye)
•What ever it hybridizes best too → fluorescent color (score what variants you have) → if you see fluorescent – it has hybridized -> now you know what variants you have and what isn't a variance |
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Term
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Definition
-assume no knowledge of the molecular cause of the disease, or where the responsible genes are located
-score SNP with this approach (group by haplotype blocks) -> take 10 random individuals (that don't have the disease) and compare to 10 individuals who are diagnosed with the disease
-if there is a significant difference within the same haplotype block amongst the diseased vs the not-diseased --> correlates with that specific disease!
-therefore we can conclude that these allele frequencies found in those with the disease are not typical of the population and is very closely linked to the mutation that causes that disease |
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Term
| Chromosome Haplotype Block |
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Definition
-use in GWAS study -> sequence all eons of the genes in the block from "Affected" patients
-if a common mutation is found; determine the function of the mutant gene
-Is the function of any gene with homology to the mutant gene known?
-Where and when is the gene expressed?
-If a mouse ortholog exists, attempt a “gene knock-out” or better introduce the mutation |
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Term
| What happens if the mutation that causes a medical condition has only arise recently? |
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Definition
then the whole genome must be sequenced and we must be bale to "see the problem"
-unfortunately for most mutations we are not yet at that level of knowledge |
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