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09-DNA.Rmd

@@ -33,7 +33,7 @@ There are several larger goals behind DNA sequencing experiments ranging from as
 
   Genomes contain more than just genes (the coding sequences that will be transcribed and translated into a protein); they also contain functional elements such as promoters, enhancers, or silencers that modulate the expression of genes [@Kellis2014]. Further, differential gene expression is the phenomenon by which cells with the same DNA sequence show different patterns of gene expression. Functional genomic analyses aim to better understand differential gene expression and the impact of genetic variation found in functional elements. For example, many human genetic variants associated with common traits and diseases are localized in or near known functional elements [@Hindorff2009]. These variants may impact gene expression due to either changes in transcription factor binding at that site, or resulting epigenetic changes, which are defined as chemical modifications of chromatin or nucleotides beyond the DNA sequence. Such epigenetic modifications, which include histone marks and DNA methylation, can alter DNA compaction and influence a functional element’s accessibility for transcriptional machinery (e.g., if the element isn't accessible, transcription may not occur; while previously the element was accessible and the gene could be transcribed). In later sections, methods that study epigenetic modifications like chromatin accessibility, DNA methylation, or binding of specific proteins will be discussed. All of these methods support functional genomic analyses and are important for better understanding differential gene expression and the impact of genetic variants located in functional elements may have on disease occurrence. A somewhat recent and high profile example of a functional genomic analysis centers again on work from the T2T Consortium. Not only did they publish a new, complete reference genome, but they also studied the epigenetic landscape in the newly resolved regions of the genome and pointed to potential newly discovered functional elements in a region previously thought to be transcriptionally inactive [@Gershman2022].
 
-* Comparative genomics
+* Comparative genomics:
 
   A common saying in the genomics field is that structure determines function and conserved structure may be constrained such that there is an important function which needs to be conserved [@Alföldi_Lindblad-Toh_2013]. Further, similarities in structure may be due to shared ancestry through the processes of evolution; therefore, some comparative genomics studies aim to infer homology or an evolutionary relationship from structural similarity [@Pearson2013]. More pertinent to the topics discussed previously, comparative genomics studies are also useful for identifying functional elements [@Taylor2006] and variants associated with disease (e.g., by comparing the genomes of those with the disease and those without it and identifying differences) [@Alföldi_Lindblad-Toh_2013; @Eichler_2019].