Structural variation in the human genome

Corresponding author: Stephen W. Scherer
The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto, MaRS Centre — East Tower, 101 College Street, Room 14-701, Ontario M5G 1L7, Canada.

变异（variants）的类型

structural abnormality: is often used if a structural variant is thought to be disease causing or is discovered as part of a disease study.
structural variants: Nothing is implied about their frequency, association with disease or phenotype, or lack thereof.

1.microscopic structural variants （∼3 Mb or more in size）

• aneuploidies 非整倍体
• rearrangements (which were often associated with disease) 重排：染色体发生断裂与别的染色体相连构成新的染色体
• heteromorphisms 异染色质：在细胞周期中，间期、早期或中、晚期，某些染色体或染色体的某些部分的固缩常较其他的染色质早些或晚些，其染色较深或较浅，具有这种固缩特性的染色体称为异染色质（heterochromatin）。具有强嗜碱性，染色深，染色质丝包装折叠紧密，与常染色质相比，异染色质是转录不活跃部分，为非活性转录区，真核生物可以通过异染色质化而关闭基因的表达 [1] 。多在晚S期复制。
• fragile sites 脆性位点

2.submicroscopic structural variants ( ∼1 kb to 3 Mb)

• CNV (Copy-number variant): A segment of DNA that is 1 kb or larger and is present at a variable copy number in comparison with a reference genome. Classes of CNVs include insertions, deletions and duplications. This definition also includes large-scale copy-number variants, which are variants that involve segments of DNA ≥50 kb
• Copy-number polymorphism: A CNV that occurs in more than 1% of the population. Originally, this definition was used to refer to all CNVs
• Segmental duplication or low-copy repeat: A segment of DNA >1 kb in size that occurs in two or more copies per haploid genome, with the different copies sharing >90% sequence identity. They are often variable in copy number and can therefore also be CNVs.
• Inversions: A segment of DNA that is reversed in orientation with respect to the rest of the chromosome. Pericentric inversions include the centromere (着丝粒), whereas paracentric inversions do not.
• Translocation: A change in position of a chromosomal segment within a genome that involves no change to the total DNA content. Translocations can be intra- or inter-chromosomal.
• Segmental uniparental disomy: Uniparental disomy describes the phenomenon in which a pair of homologous chromosomes in a diploid individual is derived from a single parent. With segmental uniparental disomy, only a portion of the chromosome pair is involved.

3. <1 kb variants

• SNP
• micro- and minisatellites
• small (usually <1 kb) insertions, deletions, inversions and duplications：Indel (insertions + deletions)