Structural variation

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Genomic structural variation is the variation in structure of an organism's chromosome. It consists of many kinds of variation in the genome of one species, and usually includes microscopic and submicroscopic types, such as deletions, duplications, copy-number variants, insertions, inversions and translocations. Originally, a structure variation affects a sequence length about 1kb to 3Mb, which is larger than SNPs and smaller than chromosome abnormality (though the definitions have some overlap). [1] However, the operational range of structural variants has widened to include events > 50bp. [2] The definition of structural variation does not imply anything about frequency or phenotypical effects. Many structural variants are associated with genetic diseases, however many are not. [3] [4] Recent research about SVs indicates that SVs are more difficult to detect than SNPs. Approximately 13% of the human genome is defined as structurally variant in the normal population, and there are at least 240 genes that exist as homozygous deletion polymorphisms in human populations, suggesting these genes are dispensable in humans. [4] Rapidly accumulating evidence indicates that structural variations can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.

Contents

Microscopic structural variation

Microscopic means that it can be detected with optical microscopes, such as aneuploidies, marker chromosome, gross rearrangements and variation in chromosome size. [5] [6] The frequency in human population is thought to be underestimated due to the fact that some of these are not actually easy to identify. These structural abnormalities exist in 1 of every 375 live births by putative information. [7]

Sub-microscopic structural variation

Sub-microscopic structural variants are much harder to detect owing to their small size. The first study in 2004 that used DNA microarrays could detect tens of genetic loci that exhibited copy number variation, deletions and duplications, greater than 100 kilobases in the human genome. [8] However, by 2015 whole genome sequencing studies could detect around 5,000 of structural variants as small as 100 base pairs encompassing approximately 20 megabases in each individual genome. [3] [4] These structural variants include deletions, tandem duplications, inversions, mobile element insertions. The mutation rate is also much higher than microscopic structural variants, estimated by two studies at 16% and 20% respectively, both of which are probably underestimates due to the challenges of accurately detecting structural variants. [3] [9] It has also been shown that the generation of spontaneous structural variants significantly increases the likelihood of generating further spontaneous single nucleotide variants or indels within 100 kilobases of the structural variation event. [3]

Copy-number variation

Copy-number variation (CNV) is a large category of structural variation, which includes insertions, deletions and duplications. In recent studies, copy-number variations are tested on people who do not have genetic diseases, using methods that are used for quantitative SNP genotyping. Results show that 28% of the suspected regions in the individuals actually do contain copy number variations. [10] [11] Also, CNVs in human genome affect more nucleotides than Single Nucleotide Polymorphism (SNP). It is also noteworthy that many of CNVs are not in coding regions. Because CNVs are usually caused by unequal recombination, widespread similar sequences such as LINEs and SINEs may be a common mechanism of CNV creation. [12] [13]

Inversion

There are several inversions known which are related to human disease. For instance, recurrent 400kb inversion in factor VIII gene is a common cause of haemophilia A, [14] and smaller inversions affecting idunorate 2-sulphatase (IDS) will cause Hunter syndrome. [15] More examples include Angelman syndrome and Sotos syndrome. However, recent research shows that one person can have 56 putative inversions, thus the non-disease inversions are more common than previously supposed. Also in this study it's indicated that inversion breakpoints are commonly associated with segmental duplications. [16] One 900 kb inversion in the chromosome 17 is under positive selection and are predicted to increase its frequency in European population. [17]

Other structural variants

More complex structural variants can occur include a combination of the above in a single event. [3] The most common type of complex structural variation are non-tandem duplications, where sequence is duplicated and inserted in inverted or direct orientation into another part of the genome. [3] Other classes of complex structural variant include deletion-inversion-deletions, duplication-inversion-duplications, and tandem duplications with nested deletions. [3] There are also cryptic translocations and segmental uniparental disomy (UPD). There are increasing reports of these variations, but are more difficult to detect than traditional variations because these variants are balanced and array-based or PCR-based methods are not able to locate them. [18]

Structural variation and phenotypes

Some genetic diseases are suspected to be caused by structural variations, but the relation is not very certain. It is not plausible to divide these variants into two classes as "normal" or "disease", because the actual output of the same variant will also vary. Also, a few of the variants are actually positively selected for (mentioned above). A series of studies have shown that gene disrupting spontaneous (de novo) CNVs disrupt genes approximately four times more frequently in autism than in controls and contribute to approximately 5–10% of cases. [3] [19] [20] [21] [22] Inherited variants also contribute to around 5–10% of cases of autism. [3]

Structural variations also have its function in population genetics. Different frequency of a same variation can be used as a genetic mark to infer relationship between populations in different areas. A complete comparison between human and chimpanzee structural variation also suggested that some of these may be fixed in one species because of its adaptative function. [23] There are also deletions related to resistance against malaria and AIDS. [24] [25] Also, some highly variable segments are thought to be caused by balancing selection, but there are also studies against this hypothesis. [26]

Database of structural variation

Some of genome browsers and bioinformatic databases have a list of structural variations in human genome with an emphasis on CNVs, and can show them in the genome browsing page, for example, UCSC Genome Browser. [27] Under the page viewing a part of the genome, there are "Common Cell CNVs" and "Structural Var" which can be enabled. On NCBI, there is a special page [28] for structural variation. In that system, both "inner" and "outer" coordinates are shown; they are both not actual breakpoints, but surmised minimal and maximum range of sequence affected by the structural variation. The types are classified as insertion, loss, gain, inversion, LOH, everted, transchr and UPD.[ citation needed ]

Methods of detection

Signatures and patterns of SVs for deletion (A), novel sequence insertion (B), inversion (C), and tandem duplication (D) in read count (RC), read-pair (RP), split-read (SR), and de novo assembly (AS) methods. Signatures of SVs in various detection methods.jpg
Signatures and patterns of SVs for deletion (A), novel sequence insertion (B), inversion (C), and tandem duplication (D) in read count (RC), read-pair (RP), split-read (SR), and de novo assembly (AS) methods.

New methods have been developed to analyze human genetic structural variation at high resolutions. The methods used to test the genome are in either a specific targeted way or in a genome wide manner. For Genome wide tests, array-based comparative genome hybridization approaches bring the best genome wide scans to find new copy number variants. [30] These techniques use DNA fragments that are labeled from a genome of interest and are hybridized, with another genome labeled differently, to arrays spotted with cloned DNA fragments. This reveals copy number differences between two genomes. [30]

For targeted genome examinations, the best assays for checking specific areas of the genome are primarily PCR based. The best established of the PCR based methods is real time quantitative polymerase chain reaction (qPCR). [30] A different approach is to specifically check certain areas that surround known segmental duplications since they are usually areas of copy number variation. [30] An SNP genotyping method that offers independent fluorescence intensities for two alleles can be used to target the nucleotides in between two copies of a segmental duplication. [30] From this, an increase in intensity from one of the alleles compared to the other can be observed.

With the development of next-generation sequencing (NGS) technology, four classes of strategies for the detection of structural variants with NGS data have been reported, with each being based on patterns that are diagnostic of different classes of SV. [31] [29] [32] [33]

See also

Related Research Articles

<span class="mw-page-title-main">Mutation</span> Alteration in the nucleotide sequence of a genome

In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements.

<span class="mw-page-title-main">Human genome</span> Complete set of nucleic acid sequences for humans

The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome and the mitochondrial genome. Human genomes include both protein-coding DNA sequences and various types of DNA that does not encode proteins. The latter is a diverse category that includes DNA coding for non-translated RNA, such as that for ribosomal RNA, transfer RNA, ribozymes, small nuclear RNAs, and several types of regulatory RNAs. It also includes promoters and their associated gene-regulatory elements, DNA playing structural and replicatory roles, such as scaffolding regions, telomeres, centromeres, and origins of replication, plus large numbers of transposable elements, inserted viral DNA, non-functional pseudogenes and simple, highly repetitive sequences. Introns make up a large percentage of non-coding DNA. Some of this non-coding DNA is non-functional junk DNA, such as pseudogenes, but there is no firm consensus on the total amount of junk DNA.

An Alu element is a short stretch of DNA originally characterized by the action of the Arthrobacter luteus (Alu) restriction endonuclease. Alu elements are the most abundant transposable elements, containing over one million copies dispersed throughout the human genome. Alu elements were thought to be selfish or parasitic DNA, because their sole known function is self reproduction. However, they are likely to play a role in evolution and have been used as genetic markers. They are derived from the small cytoplasmic 7SL RNA, a component of the signal recognition particle. Alu elements are highly conserved within primate genomes and originated in the genome of an ancestor of Supraprimates.

Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.

<span class="mw-page-title-main">Haploinsufficiency</span> Concept in genetics

Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type phenotype. Haploinsufficiency may arise from a de novo or inherited loss-of-function mutation in the variant allele, such that it yields little or no gene product. Although the other, standard allele still produces the standard amount of product, the total product is insufficient to produce the standard phenotype. This heterozygous genotype may result in a non- or sub-standard, deleterious, and (or) disease phenotype. Haploinsufficiency is the standard explanation for dominant deleterious alleles.

Indel (insertion-deletion) is a molecular biology term for an insertion or deletion of bases in the genome of an organism. Indels ≥ 50 bases in length are classified as structural variants.

<span class="mw-page-title-main">Copy number variation</span> Repeated DNA variation between individuals

Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Copy number variation is a type of structural variation: specifically, it is a type of duplication or deletion event that affects a considerable number of base pairs. Approximately two-thirds of the entire human genome may be composed of repeats and 4.8–9.5% of the human genome can be classified as copy number variations. In mammals, copy number variations play an important role in generating necessary variation in the population as well as disease phenotype.

<span class="mw-page-title-main">Human genetic variation</span> Genetic diversity in human populations

Human genetic variation is the genetic differences in and among populations. There may be multiple variants of any given gene in the human population (alleles), a situation called polymorphism.

<span class="mw-page-title-main">1000 Genomes Project</span> International research effort on genetic variation

The 1000 Genomes Project, launched in January 2008, was an international research effort to establish by far the most detailed catalogue of human genetic variation. Scientists planned to sequence the genomes of at least one thousand anonymous participants from a number of different ethnic groups within the following three years, using newly developed technologies which were faster and less expensive. In 2010, the project finished its pilot phase, which was described in detail in a publication in the journal Nature. In 2012, the sequencing of 1092 genomes was announced in a Nature publication. In 2015, two papers in Nature reported results and the completion of the project and opportunities for future research.

Low copy repeats (LCRs), also known as segmental duplications (SDs), are DNA sequences present in multiple locations within a genome that share high levels of sequence identity.

Koolen–De Vries syndrome (KdVS), also known as 17q21.31 microdeletion syndrome, is a rare genetic disorder caused by a deletion of a segment of chromosome 17 which contains six genes. This deletion syndrome was discovered independently in 2006 by three different research groups.

DECIPHER is a web-based resource and database of genomic variation data from analysis of patient DNA. It documents submicroscopic chromosome abnormalities and pathogenic sequence variants, from over 25000 patients and maps them to the human genome using Ensembl or UCSC Genome Browser. In addition it catalogues the clinical characteristics from each patient and maintains a database of microdeletion/duplication syndromes, together with links to relevant scientific reports and support groups.

<span class="mw-page-title-main">8p23.1 duplication syndrome</span> Medical condition

8p23.1 duplication syndrome is a rare genetic disorder caused by a duplication of a region from human chromosome 8. This duplication syndrome has an estimated prevalence of 1 in 64,000 births and is the reciprocal of the 8p23.1 deletion syndrome. The 8p23.1 duplication is associated with a variable phenotype including one or more of speech delay, developmental delay, mild dysmorphism, with prominent forehead and arched eyebrows, and congenital heart disease (CHD).

Non-allelic homologous recombination (NAHR) is a form of homologous recombination that occurs between two lengths of DNA that have high sequence similarity, but are not alleles.

esophageal candidiasis1q21.1 deletion syndrome is a rare aberration of chromosome 1. A human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 deletion syndrome, one chromosome of the pair is not complete, because a part of the sequence of the chromosome is missing. One chromosome has the normal length and the other is too short.

<span class="mw-page-title-main">Charles Lee (scientist)</span>

Charles Lee is Director and Professor of The Jackson Laboratory for Genomic Medicine, The Robert Alvine Family Endowed Chair and a board certified clinical cytogeneticist who has an active research program in the identification and characterization of structural genomic variants using advanced technology platforms. His laboratory was the first to describe genome-wide structural genomic variants among humans with the subsequent development of two human CNV maps that are now actively used in the diagnoses of array based genetic tests. Lee is also currently the President of the Human Genome Organisation (HUGO).

<span class="mw-page-title-main">End-sequence profiling</span>

End-sequence profiling (ESP) is a method based on sequence-tagged connectors developed to facilitate de novo genome sequencing to identify high-resolution copy number and structural aberrations such as inversions and translocations.

<span class="mw-page-title-main">Structural variation in the human genome</span> Genomic alterations, varying between individuals

Structural variation in the human genome is operationally defined as genomic alterations, varying between individuals, that involve DNA segments larger than 1 kilo base (kb), and could be either microscopic or submicroscopic. This definition distinguishes them from smaller variants that are less than 1 kb in size such as short deletions, insertions, and single nucleotide variants.

ANNOVAR is a bioinformatics software tool for the interpretation and prioritization of single nucleotide variants (SNVs), insertions, deletions, and copy number variants (CNVs) of a given genome.

Human somatic variations are somatic mutations both at early stages of development and in adult cells. These variations can lead either to pathogenic phenotypes or not, even if their function in healthy conditions is not completely clear yet.

References

  1. ↑ Feuk, Lars; Carson, Andrew R.; Scherer, Stephen W. (2006). "Structural variation in the human genome". Nature Reviews Genetics. 7 (2): 85–97. doi:10.1038/nrg1767. PMID   16418744. S2CID   17255998.
  2. ↑ Alkan, Can; Coe, Bradley P.; Eichler, Evan E. (2011-03-01). "Genome structural variation discovery and genotyping". Nature Reviews Genetics. 12 (5): 363–376. doi:10.1038/nrg2958. ISSN   1471-0056. PMC   4108431 . PMID   21358748.
  3. 1 2 3 4 5 6 7 8 9 Brandler, William M.; Antaki, Danny; Gujral, Madhusudan; Noor, Amina; Rosanio, Gabriel; Chapman, Timothy R.; Barrera, Daniel J.; Lin, Guan Ning; Malhotra, Dheeraj; Watts, Amanda C.; Wong, Lawrence C.; Estabillo, Jasper A.; Gadomski, Therese E.; Hong, Oanh; Fajardo, Karin V. Fuentes; Bhandari, Abhishek; Owen, Renius; Baughn, Michael; Yuan, Jeffrey; Solomon, Terry; Moyzis, Alexandra G.; Maile, Michelle S.; Sanders, Stephan J.; Reiner, Gail E.; Vaux, Keith K.; Strom, Charles M.; Zhang, Kang; Muotri, Alysson R.; Akshoomoff, Natacha; Leal, Suzanne M.; Pierce, Karen; Courchesne, Eric; Iakoucheva, Lilia M.; Corsello, Christina; Sebat, Jonathan (24 March 2016). "Frequency and Complexity of De Novo Structural Mutation in Autism". The American Journal of Human Genetics. 98 (4): 667–79. doi:10.1016/j.ajhg.2016.02.018. PMC   4833290 . PMID   27018473.
  4. 1 2 3 Sudmant, Peter H.; Rausch, Tobias; Gardner, Eugene J.; Handsaker, Robert E.; Abyzov, Alexej; Huddleston, John; Zhang, Yan; Ye, Kai; Jun, Goo; Hsi-Yang Fritz, Markus; Konkel, Miriam K.; Malhotra, Ankit; Stütz, Adrian M.; Shi, Xinghua; Paolo Casale, Francesco; Chen, Jieming; Hormozdiari, Fereydoun; Dayama, Gargi; Chen, Ken; Malig, Maika; Chaisson, Mark J. P.; Walter, Klaudia; Meiers, Sascha; Kashin, Seva; Garrison, Erik; Auton, Adam; Lam, Hugo Y. K.; Jasmine Mu, Xinmeng; Alkan, Can; Antaki, Danny; Bae, Taejeong; Cerveira, Eliza; Chines, Peter; Chong, Zechen; Clarke, Laura; Dal, Elif; Ding, Li; Emery, Sarah; Fan, Xian; Gujral, Madhusudan; Kahveci, Fatma; Kidd, Jeffrey M.; Kong, Yu; Lameijer, Eric-Wubbo; McCarthy, Shane; Flicek, Paul; Gibbs, Richard A.; Marth, Gabor; Mason, Christopher E.; Menelaou, Androniki; Muzny, Donna M.; Nelson, Bradley J.; Noor, Amina; Parrish, Nicholas F.; Pendleton, Matthew; Quitadamo, Andrew; Raeder, Benjamin; Schadt, Eric E.; Romanovitch, Mallory; Schlattl, Andreas; Sebra, Robert; Shabalin, Andrey A.; Untergasser, Andreas; Walker, Jerilyn A.; Wang, Min; Yu, Fuli; Zhang, Chengsheng; Zhang, Jing; Zheng-Bradley, Xiangqun; Zhou, Wanding; Zichner, Thomas; Sebat, Jonathan; Batzer, Mark A.; McCarroll, Steven A.; Mills, Ryan E.; Gerstein, Mark B.; Bashir, Ali; Stegle, Oliver; Devine, Scott E.; Lee, Charles; Eichler, Evan E.; Korbel, Jan O. (30 September 2015). "An integrated map of structural variation in 2,504 human genomes". Nature. 526 (7571): 75–81. Bibcode:2015Natur.526...75.. doi:10.1038/nature15394. PMC   4617611 . PMID   26432246.
  5. ↑ Reich, David E.; Schaffner, Stephen F.; Daly, Mark J.; McVean, Gil; Mullikin, James C.; Higgins, John M.; Richter, Daniel J.; Lander, Eric S.; Altshuler, David (2002). "Human genome sequence variation and the influence of gene history, mutation and recombination". Nature Genetics. 32 (1): 135–42. doi:10.1038/ng947. PMID   12161752. S2CID   16822751.
  6. ↑ Gripenberg, Ulla (1964). "Size variation and orientation of the human Y chromosome". Chromosoma. 15 (5): 618–29. doi:10.1007/BF00319995. PMID   14333154. S2CID   26549548.
  7. ↑ Wyandt, H. E.; Tonk, V. S. (2004). Atlas of Human Chromosome Heteromorphisms. Netherlands: Kluwer Academic. ISBN   978-90-481-6296-3.[ page needed ]
  8. ↑ Sebat, J. (23 July 2004). "Large-Scale Copy Number Polymorphism in the Human Genome". Science. 305 (5683): 525–528. Bibcode:2004Sci...305..525S. doi:10.1126/science.1098918. PMID   15273396. S2CID   20357402.
  9. ↑ Kloosterman, Wigard P.; Francioli, Laurent C.; Hormozdiari, Fereydoun; Marschall, Tobias; Hehir-Kwa, Jayne Y.; Abdellaoui, Abdel; Lameijer, Eric-Wubbo; Moed, Matthijs H.; Koval, Vyacheslav; Renkens, Ivo; van Roosmalen, Markus J.; Arp, Pascal; Karssen, Lennart C.; Coe, Bradley P.; Handsaker, Robert E.; Suchiman, Eka D.; Cuppen, Edwin; Thung, Djie Tjwan; McVey, Mitch; Wendl, Michael C.; Uitterlinden, André; van Duijn, Cornelia M.; Swertz, Morris A.; Wijmenga, Cisca; van Ommen, GertJan B.; Slagboom, P. Eline; Boomsma, Dorret I.; Schönhuth, Alexander; Eichler, Evan E.; de Bakker, Paul I.W.; Ye, Kai; Guryev, Victor (June 2015). "Characteristics of de novo structural changes in the human genome". Genome Research. 25 (6): 792–801. doi:10.1101/gr.185041.114. PMC   4448676 . PMID   25883321.
  10. ↑ Sebat, J.; Lakshmi, B; Troge, J; Alexander, J; Young, J; Lundin, P; Månér, S; Massa, H; et al. (2004). "Large-Scale Copy Number Polymorphism in the Human Genome". Science. 305 (5683): 525–8. Bibcode:2004Sci...305..525S. doi:10.1126/science.1098918. PMID   15273396. S2CID   20357402.
  11. ↑ Iafrate, A John; Feuk, Lars; Rivera, Miguel N; Listewnik, Marc L; Donahoe, Patricia K; Qi, Ying; Scherer, Stephen W; Lee, Charles (2004). "Detection of large-scale variation in the human genome". Nature Genetics. 36 (9): 949–51. doi: 10.1038/ng1416 . PMID   15286789.
  12. ↑ Lupski, James R. (2010). "Retrotransposition and Structural Variation in the Human Genome". Cell. 141 (7): 1110–2. doi: 10.1016/j.cell.2010.06.014 . PMID   20602993. S2CID   2047696.
  13. ↑ Lam, Hugo YK; Mu, Xinmeng Jasmine; Stutz, Adrian M; Tanzer, Andrea; Cayting, Philip D; Snyder, Michael; Kim, Philip M; Korbel, Jan O; Gerstein, Mark B (2010). "Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library". Nature Biotechnology. 28 (1): 47–55. doi:10.1038/nbt.1600. PMC   2951730 . PMID   20037582.
  14. ↑ Lakich, Delia; Kazazian, Haig H.; Antonarakis, Stylianos E.; Gitschier, Jane (1993). "Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A". Nature Genetics. 5 (3): 236–41. doi:10.1038/ng1193-236. PMID   8275087. S2CID   25636383.
  15. ↑ Bondeson, Maire-Louise; Dahl, Niklas; Malmgren, Helena; Kleijer, Wim J.; Tönnesen, Tönne; Carlberg, Britt-Marie; Pettersson, Ulf (1995). "Inversion of the IDS gene resulting from recombination with IDS-related sequences in a common cause of the Hunter syndrome". Human Molecular Genetics. 4 (4): 615–21. doi:10.1093/hmg/4.4.615. PMID   7633410.
  16. ↑ Tuzun, Eray; Sharp, Andrew J; Bailey, Jeffrey A; Kaul, Rajinder; Morrison, V Anne; Pertz, Lisa M; Haugen, Eric; Hayden, Hillary; et al. (2005). "Fine-scale structural variation of the human genome". Nature Genetics. 37 (7): 727–32. doi:10.1038/ng1562. PMID   15895083. S2CID   14162962.
  17. ↑ Stefansson, Hreinn; Helgason, Agnar; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Masson, Gisli; Barnard, John; Baker, Adam; Jonasdottir, Aslaug; et al. (2005). "A common inversion under selection in Europeans". Nature Genetics. 37 (2): 129–37. doi:10.1038/ng1508. PMID   15654335. S2CID   120515.
  18. ↑ Sung, Wing-Kin (18 May 2017). Algorithms for next-generation sequencing. Boca Raton. p. 215. ISBN   978-1-4665-6551-7. OCLC   987790994.{{cite book}}: CS1 maint: location missing publisher (link)
  19. ↑ Sebat, J.; Lakshmi, B.; Malhotra, D.; Troge, J.; Lese-Martin, C.; Walsh, T.; Yamrom, B.; Yoon, S.; Krasnitz, A.; Kendall, J.; Leotta, A.; Pai, D.; Zhang, R.; Lee, Y.-H.; Hicks, J.; Spence, S. J.; Lee, A. T.; Puura, K.; Lehtimaki, T.; Ledbetter, D.; Gregersen, P. K.; Bregman, J.; Sutcliffe, J. S.; Jobanputra, V.; Chung, W.; Warburton, D.; King, M.-C.; Skuse, D.; Geschwind, D. H.; Gilliam, T. C.; Ye, K.; Wigler, M. (20 April 2007). "Strong Association of De Novo Copy Number Mutations with Autism". Science. 316 (5823): 445–449. Bibcode:2007Sci...316..445S. doi:10.1126/science.1138659. PMC   2993504 . PMID   17363630.
  20. ↑ Pinto, Dalila; Delaby, Elsa; Merico, Daniele; Barbosa, Mafalda; Merikangas, Alison; Klei, Lambertus; Thiruvahindrapuram, Bhooma; Xu, Xiao; Ziman, Robert; Wang, Zhuozhi; Vorstman, Jacob A.S.; Thompson, Ann; Regan, Regina; Pilorge, Marion; Pellecchia, Giovanna; Pagnamenta, Alistair T.; Oliveira, Bárbara; Marshall, Christian R.; Magalhaes, Tiago R.; Lowe, Jennifer K.; Howe, Jennifer L.; Griswold, Anthony J.; Gilbert, John; Duketis, Eftichia; Dombroski, Beth A.; De Jonge, Maretha V.; Cuccaro, Michael; Crawford, Emily L.; Correia, Catarina T.; et al. (May 2014). "Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders". The American Journal of Human Genetics. 94 (5): 677–694. doi:10.1016/j.ajhg.2014.03.018. PMC   4067558 . PMID   24768552.
  21. ↑ Levy, Dan; Ronemus, Michael; Yamrom, Boris; Lee, Yoon-ha; Leotta, Anthony; Kendall, Jude; Marks, Steven; Lakshmi, B.; Pai, Deepa; Ye, Kenny; Buja, Andreas; Krieger, Abba; Yoon, Seungtai; Troge, Jennifer; Rodgers, Linda; Iossifov, Ivan; Wigler, Michael (June 2011). "Rare De Novo and Transmitted Copy-Number Variation in Autistic Spectrum Disorders". Neuron. 70 (5): 886–897. doi: 10.1016/j.neuron.2011.05.015 . PMID   21658582. S2CID   11132936.
  22. ↑ Sanders, Stephan J.; Ercan-Sencicek, A. Gulhan; Hus, Vanessa; Luo, Rui; Murtha, Michael T.; Moreno-De-Luca, Daniel; Chu, Su H.; Moreau, Michael P.; Gupta, Abha R.; Thomson, Susanne A.; Mason, Christopher E.; Bilguvar, Kaya; Celestino-Soper, Patricia B.S.; Choi, Murim; Crawford, Emily L.; Davis, Lea; Davis Wright, Nicole R.; Dhodapkar, Rahul M.; DiCola, Michael; DiLullo, Nicholas M.; Fernandez, Thomas V.; Fielding-Singh, Vikram; Fishman, Daniel O.; Frahm, Stephanie; Garagaloyan, Rouben; Goh, Gerald S.; Kammela, Sindhuja; Klei, Lambertus; Lowe, Jennifer K.; Lund, Sabata C.; McGrew, Anna D.; Meyer, Kyle A.; Moffat, William J.; Murdoch, John D.; O'Roak, Brian J.; Ober, Gordon T.; Pottenger, Rebecca S.; Raubeson, Melanie J.; Song, Youeun; Wang, Qi; Yaspan, Brian L.; Yu, Timothy W.; Yurkiewicz, Ilana R.; Beaudet, Arthur L.; Cantor, Rita M.; Curland, Martin; Grice, Dorothy E.; Günel, Murat; Lifton, Richard P.; Mane, Shrikant M.; Martin, Donna M.; Shaw, Chad A.; Sheldon, Michael; Tischfield, Jay A.; Walsh, Christopher A.; Morrow, Eric M.; Ledbetter, David H.; Fombonne, Eric; Lord, Catherine; Martin, Christa Lese; Brooks, Andrew I.; Sutcliffe, James S.; Cook, Edwin H.; Geschwind, Daniel; Roeder, Kathryn; Devlin, Bernie; State, Matthew W. (June 2011). "Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism". Neuron. 70 (5): 863–885. doi:10.1016/j.neuron.2011.05.002. PMC   3939065 . PMID   21658581.
  23. ↑ Johnson, Matthew E.; Viggiano, Luigi; Bailey, Jeffrey A.; Abdul-Rauf, Munah; Goodwin, Graham; Rocchi, Mariano; Eichler, Evan E. (2001). "Positive selection of a gene family during the emergence of humans and African apes". Nature. 413 (6855): 514–9. Bibcode:2001Natur.413..514J. doi:10.1038/35097067. PMID   11586358. S2CID   4327069.
  24. ↑ Redon, Richard; Ishikawa, Shumpei; Fitch, Karen R.; Feuk, Lars; Perry, George H.; Andrews, T. Daniel; Fiegler, Heike; Shapero, Michael H.; et al. (2006). "Global variation in copy number in the human genome". Nature. 444 (7118): 444–54. Bibcode:2006Natur.444..444R. doi:10.1038/nature05329. PMC   2669898 . PMID   17122850.
  25. ↑ Gonzalez, E.; Kulkarni, H; Bolivar, H; Mangano, A; Sanchez, R; Catano, G; Nibbs, RJ; Freedman, BI; et al. (2005). "The Influence of CCL3L1 Gene-Containing Segmental Duplications on HIV-1/AIDS Susceptibility". Science. 307 (5714): 1434–40. Bibcode:2005Sci...307.1434G. doi:10.1126/science.1101160. PMID   15637236. S2CID   8815153.
  26. ↑ Bubb, K. L.; Bovee, D; Buckley, D; Haugen, E; Kibukawa, M; Paddock, M; Palmieri, A; Subramanian, S; et al. (2006). "Scan of Human Genome Reveals No New Loci Under Ancient Balancing Selection". Genetics. 173 (4): 2165–77. doi:10.1534/genetics.106.055715. PMC   1569689 . PMID   16751668.
  27. ↑ "Human hg38 chr1:11,102,837-11,267,747 UCSC Genome Browser v374".
  28. ↑ "Overview of Structural Variation".
  29. 1 2 Tattini, Lorenzo; D'Aurizio, Romina; Magi, Alberto (2015). "Detection of genomic structural variants from next-generation sequencing data". Frontiers in Bioengineering and Biotechnology. 3 (92): 92. doi: 10.3389/fbioe.2015.00092 . PMC   4479793 . PMID   26161383.
  30. 1 2 3 4 5 Feuk, L.; Carson, A.R.; Schere, S.W. (2006). "Structural variation in the human genome". Nature Reviews Genetics. 7 (2): 85–97. doi:10.1038/nrg1767. PMID   16418744. S2CID   17255998.
  31. ↑ Korbel JO, Urban AE, Affourtit JP, Godwin B, Grubert F, Simons JF, Kim PM, Palejev D, Carriero NJ, Du L, Taillon BE, Chen Z, Tanzer A, Saunders AC, Chi J, Yang F, Carter NP, Hurles ME, Weissman SM, Harkins TT, Gerstein MB, Egholm M, Snyder M (October 2007). "Paired-end mapping reveals extensive structural variation in the human genome". Science. 318 (5849): 420–6. Bibcode:2007Sci...318..420K. doi:10.1126/science.1149504. PMC   2674581 . PMID   17901297.
  32. ↑ Alkan, Can; Coe, Bradley P.; Eichler, Evan E. (2011). "Genome structural variation discovery and genotyping". Nature Reviews Genetics. 12 (5): 363–376. doi:10.1038/nrg2958. PMC   4108431 . PMID   21358748.
  33. ↑ Kuzniar, Arnold; Maassen, Jason; Verhoeven, Stefan; Santuari, Luca; Shneider, Carl; Kloosterman, Wigard P.; de Ridder, Jeroen (2020). "sv-callers: a highly portable parallel workflow for structural variant detection in whole-genome sequence data". PeerJ. 8 (5): 2167–8359. doi: 10.7717/peerj.8214 . PMC   6951283 . PMID   31934500.
  34. ↑ Ebert P, Audano PA, Zhu Q, Rodriguez-Martin B, Porubsky D, Bonder MJ, Sulovari A, Ebler J, Zhou W, Serra Mari R, Yilmaz F, Zhao X, Hsieh P, Lee J, Kumar S, Lin J, Rausch T, Chen Y, Ren J, Santamarina M, Höps W, Ashraf H, Chuang NT, Yang X, Munson KM, Lewis AP, Fairley S, Tallon LJ, Clarke WE, Basile AO, Byrska-Bishop M, Corvelo A, Evani US, Lu TY, Chaisson MJ, Chen J, Li C, Brand H, Wenger AM, Ghareghani M, Harvey WT, Raeder B, Hasenfeld P, Regier AA, Abel HJ, Hall IM, Flicek P, Stegle O, Gerstein MB, Tubio JM, Mu Z, Li YI, Shi X, Hastie AR, Ye K, Chong Z, Sanders AD, Zody MC, Talkowski ME, Mills RE, Devine SE, Lee C, Korbel JO, Marschall T, Eichler EE (April 2021). "Haplotype-resolved diverse human genomes and integrated analysis of structural variation". Science. 372 (6537). doi: 10.1126/science.abf7117 . PMC   8026704 . PMID   33632895.
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