Leveraging large genomic datasets to illuminate the pathobiology of autism spectrum disorders

摘要

a The majority of genetic variation in the human genome is common (population frequency ≥ 1%, blue). These variants are transmitted from parents to offspring via Mendelian inheritance patterns. A smaller proportion is rare (≤1%, purple) and also transmitted from parents. ∼70 variants are de novo (red), observed only in the child, but not in either parent. b The impact of single-nucleotide variants (SNVs) and small (≤50 bp) insertion/deletions (indels) depends on their location in the genome. In the 1.5% of the genome that encodes proteins (the exome), these variants can either be synonymous (no change to the resulting protein), missense (a single amino acid is changed in the protein with variable functional impact), or protein-truncating (leads to nonsense-mediated decay and no protein). Variants and their consequences (red stars) are shown on the father’s allele, but can also arise on the maternal allele. c Copy number variants (CNVs) are large (≥50 bp to millions of nucleotides) deletions (resulting in no protein), or duplications (potentially resulting in excess protein). Figure adapted from Sanders [81] with author permission.