Podcast
Questions and Answers
What is the purpose of Genome Wide Association Studies (GWAS)?
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 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?
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?
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?
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?
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?
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?
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?
'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?
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.
Studying That Suits You
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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.
