| Genetic variant |
Description and comments |
| Single nucleotide variant (SNV) |
A genetic point mutation. SNVs have potential to cause downstream effects on gene function. |
| Single nucleotide polymorphism (SNP) |
SNVs that occur in >1% of the population are SNPs. There are currently 720 million known SNPs in the human genome (as per NCBI dbSNP database build 155). |
| Copy number variant (CNV) |
A stretch of DNA greater than 1kilobase in length that varies in copy numbers. These can be copy number losses (deletions or null genotypes) or gains (insertions or duplications) and can range from being simple in structure to involving complete gains or losses of genetic sequences. CNV have the potential to affect the function of multiple genes simultaneously. |
| De novo mutations |
Rare non-inherited genetic variants and have potential to be pathogenic. |
| Study methodology |
Description and comments |
| Candidate gene study |
Assess SNPs known to be involved in regulating the function of pre-defined candidate genes and test for a statistical correlation with the disease of interest. |
| Genome-wide Association Study (GWAS) |
Utilize a genome-wide and hypothesis-free approach. DNA is genotyped on an array to assess hundreds of thousands of known index SNPs within large cohorts and highlight genetic variants that may be associated with a disease or trait of focus. The index SNPs on GWAS arrays represents all SNPs in high linkage disequilibrium (LD) with the index SNP. As a result, the associations identified in GWAS are indirect as the casual SNP is often not the SNP identified in the GWAS, but rather a SNP in high LD. |
| Whole-exome sequencing (WES) & whole genome sequencing (WGS) |
WGS sequences the entire DNA of the individual genome. WES is a targeted version of WGS that only sequences the exomes (protein coding regions) of the genome. These studies can detect rare or de novo variants associated with disease. |
| Transcriptomics |
Analyses RNA transcripts, their expression, function, and degradation. RNA transcripts include both coding and non-coding RNA. Messenger RNA (mRNA) is a coding RNA. Non-coding RNA have no protein-coding potential, however, can be involved in post-translational regulation and other mechanisms that affect gene expression. An example of short non-coding RNAs (40-200 nucleotides in length) is microRNA (miRNAs). RNAs >200 nucleotides in length include ribosomal RNA (rRNA) and long non-coding RNA (lncRNA). The quantity of RNA transcripts is measured via microarrays or RNA sequencing for a given gene in specific tissues, providing a direct indication of gene transcription levels. |
| Epigenetics |
Assess heritable alterations in the DNA that are not due to sequence changes in the genome. Epigenetic modifications occur primarily through DNA methylation, histone modification and miRNA, and are influenced by combined environmental exposures and genetic predispositions. Gene expression is regulated at both transcription events (DNA methylation and histone modification) and translation events (miRNA). Epigenetic changes often affect chromatin structure and accessibility which affect gene expression and protein transcription. Methylation often occurs at cytosines followed by guanosine residuals (CpG sites). DNA methylation can be studied using DNA methylation arrays and high-throughput sequencing. Chromatin accessibility assay ATAC-seq is used to profile histone modification. |
