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Questions and Answers
What is the purpose of Genome Wide Association Studies (GWAS)?
What does it mean for certain SNPs to be 'associated' with a disease in the context of GWAS?
What does a Manhattan Plot typically depict in a GWAS?
During the initial discovery phase of a GWAS, what is typically done with genotyped SNPs?
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What is the difference between the initial discovery phase and the replication phase of a GWAS?
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What does the X-axis typically represent in a Manhattan Plot in a GWAS?
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What is meant by 'genotype up to 1X10^6 SNPs' in the context of a GWAS?
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What is the significance of 'strict standards of statistical significance' in GWAS?
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'Each dot represents a SNP', this statement relates to which visual representation from a GWAS?
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What is being compared between 'cases' and 'controls' during the initial discovery phase of a GWAS?
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Study Notes
Genetic Variation
- The Human Genome Project (1990-2003) sequenced 3x10^9 bp and identified ~22,300 genes.
- Genetic variation refers to differences in the sequence of DNA between individuals.
- Despite being 99.9% identical, individuals have ~3 million inter-individual differences.
- The comprehensive catalog of human genomic variation was created from 2008-2015.
Single Nucleotide Polymorphism (SNP)
- SNPs occur when a single nucleotide is altered in the DNA sequence.
- SNPs are SNVs that occur in >1% of the population.
- They occur every ~1000 bp and make up ~90% of human genome variation.
- An average genome includes ~3 million SNPs from the reference genome.
Consequences of SNVs
- SNVs can be disease-causing if they occur within a gene or in a regulatory region.
- They can be used for personalized medicine to predict individual susceptibility to toxins or response to drugs.
- SNVs can be used as genomic markers to identify genes associated with complex diseases.
- Polygenic risk scores (PRS) can be used to calculate the risk of developing a disease.
Multifactorial Inheritance/Complex Diseases
- Complex diseases, such as heart disease, type 2 diabetes, and obesity, do not have a single genetic cause.
- They are influenced by multiple genes (polygenic) in combination with lifestyle and environmental factors.
- Multifactorial inheritance does not follow Mendelian patterns of inheritance.
Genome-Wide Association Studies (GWAS)
- GWAS is a hypothesis-free approach to identify genes associated with complex diseases.
- GWAS tests thousands or millions of genetic variants scattered throughout the human genome.
- The initial discovery phase involves a case-control study to identify frequency differences between cases and controls.
- The replication phase involves testing the identified SNPs in a larger population.
Manhattan Plot
- A Manhattan plot is a graphical representation of GWAS results.
- Each dot represents a SNP, with the X-axis showing genomic location and the Y-axis showing association level as –log10 (p).
- The plot shows each SNP in chromosomal order and highlights SNPs that meet strict standards of statistical significance.
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Description
Test your knowledge on genetic variation, SNPs, GWAS, and the Human Genome Project in this quiz based on a lecture by Evy Bashiardes, PhD. Explore topics such as genome variations and the analogy of the genome to a book with typos.
