Genomes and variants

Background One of the defining achievements of the early 21st century is the sequencing and alignment of more than 90% of the human genome. Of course, there is not a single human genome: individuals differ from each other by about 0.1% and from other primates by about 1%. Variation comes in many different forms, including single base changes and copy number changes in large segments of DNA. Even more challenging than sequencing the whole genome is documenting and understanding the clinical significance of human sequence variation. We are still very early in our understanding of the human genome. Content Beginning with a historical perspective, the structure of the human genome is described in detail followed by comparison to other interesting species. Then different types of genomic variation are covered, including single base changes (substitutions, deletions, insertions), copy number variations, translocations and fusions, short tandem repeats of different size and number, and larger repetitive segments, some of which can hop around the genome as transposons. The function of different genomic elements is considered along with many different classes of RNA transcribed from the DNA. How to name all the different genes, variants, and elements is a daunting task, and accepted nomenclature is presented. Many databases are available to mine accumulated genomic information. We end with a description of basic informatics tools that provide a pipeline from the raw data of massively parallel DNA sequencing to finished sequence with annotations on the variations that are observed.