Key Points
-
Human and great ape genomes show an enrichment of large, interspersed and highly identical duplications, known as segmental duplications, when compared with other species.
-
Primate segmental duplications are organized into complicated structures (duplication hubs) that are made up of many independent duplication events.
-
Analyses of the boundaries between segmental duplications suggest distinct mechanisms for their origin, including Alu repetitive elements, mediated transposition and mechanisms that are mediated by both homology-driven and non-homology-driven events.
-
Segmental duplications are enriched at the breakpoints of chromosomal synteny between human and mammalian genomes.
-
Evolutionary analyses suggest spatial and temporal biases in the emergence of SDs, indicating distinct waves of duplication during the evolution of the human and great ape genomes.
-
Both fusion genes and genes showing signatures of adaptive evolution have been documented among some of the most abundant and recently duplicated intrachromosomal duplications.
-
Segmental duplications mediate rare structural rearrangements and common copy-number polymorphisms that are associated with disease and disease susceptibility.
Abstract
Compared with other mammals, the genomes of humans and other primates show an enrichment of large, interspersed segmental duplications (SDs) with high levels of sequence identity. Recent evidence has begun to shed light on the origin of primate SDs, pointing to a complex interplay of mechanisms and indicating that distinct waves of duplication took place during primate evolution. There is also evidence for a strong association between duplication, genomic instability and large-scale chromosomal rearrangements. Exciting new findings suggest that SDs have not only created novel primate gene families, but might have also influenced current human genic and phenotypic variation on a previously unappreciated scale. A growing number of examples link natural human genetic variation of these regions to susceptibility to common disease.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bailey, J. A., Yavor, A. M., Massa, H. F., Trask, B. J. & Eichler, E. E. Segmental duplications: organization and impact within the current human genome project assembly. Genome Res. 11, 1005–1017 (2001).
International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).
Cheung, J. et al. Recent segmental and gene duplications in the mouse genome. Genome Biol. 4, R47 (2003).
Tuzun, E., Bailey, J. A. & Eichler, E. E. Recent segmental duplications in the working draft assembly of the brown Norway rat. Genome Res. 14, 493–506 (2004).
Bailey, J. A., Church, D. M., Ventura, M., Rocchi, M. & Eichler, E. E. Analysis of segmental duplications and genome assembly in the mouse. Genome Res. 14, 789–801 (2004).
Cheng, Z. et al. A genome-wide comparison of recent chimpanzee and human segmental duplications. Nature 437, 88–93 (2005).
She, X. et al. A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a Great-Ape expansion of intrachromosomal duplications. Genome Res. 16, 576–583 (2006).
Cheung, J. et al. Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence. Genome Biol. 4, R25 (2003).
Zhang, L., Lu, H. H., Chung, W. Y., Yang, J. & Li, W. H. Patterns of segmental duplication in the human genome. Mol. Biol. Evol. 22, 135–141 (2005).
Bailey, J. A. et al. Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22. Am. J. Hum. Genet. 70, 83–100 (2002).
She, X. et al. The structure and evolution of centromeric transition regions within the human genome. Nature 430, 857–864 (2004).
She, X. et al. Shotgun sequence assembly and recent segmental duplications within the human genome. Nature 431, 927–930 (2004).
Bailey, J. A. et al. Recent segmental duplications in the human genome. Science 297, 1003–1007 (2002).
International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 431, 931–945 (2004).
Eichler, E. E., Clark, R. A. & She, X. An assessment of the sequence gaps: unfinished business in a finished human genome. Nature Rev. Genet. 5, 345–354 (2004).
Courseaux, A. & Nahon, J. L. Birth of two chimeric genes in the Hominidae lineage. Science 291, 1293–1297 (2001).
Horvath, J. E. et al. Punctuated duplication seeding events during the evolution of human chromosome 2p11. Genome Res 15, 914–927 (2005).
Johnson, M. E. et al. Positive selection of a gene family during the emergence of humans and African apes. Nature 413, 514–519 (2001).
Courseaux, A. et al. Segmental duplications in euchromatic regions of human chromosome 5: a source of evolutionary instability and transcriptional innovation. Genome Res. 13, 369–381 (2003).
Stankiewicz, P., Shaw, C. J., Withers, M., Inoue, K. & Lupski, J. R. Serial segmental duplications during primate evolution result in complex human genome architecture. Genome Res. 14, 2209–2220 (2004).
Ciccarelli, F. D. et al. Complex genomic rearrangements lead to novel primate gene function. Genome Res. 15, 343–351 (2005).
Newman, T. L. et al. A genome-wide survey of structural variation between human and chimpanzee. Genome Res. 15, 1344–1356 (2005).
Humphray, S. J. et al. DNA sequence and analysis of human chromosome 9. Nature 429, 369–374 (2004).
Kirsch, S. et al. Interchromosomal segmental duplications of the pericentromeric region on the human Y chromosome. Genome Res. 15, 195–204 (2005).
Guy, J. et al. Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10p. Genome Res. 13, 159–172 (2003).
Guy, J. et al. Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10q. Hum. Mol. Genet. 9, 2029–2042 (2000).
Brun, M. E., Ruault, M., Ventura, M., Roizes, G. & De Sario, A. Juxtacentromeric region of human chromosome 21: a boundary between centromeric heterochromatin and euchromatic chromosome arms. Gene 312, 41–50 (2003).
Horvath, J., Schwartz, S. & Eichler, E. The mosaic structure of a 2p11 pericentromeric segment: a strategy for characterizing complex regions of the human genome. Genome Res 10, 839–852 (2000).
Eichler, E. E. et al. Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity. Hum. Mol. Genet. 6, 991–1002 (1997).
Riethman, H. C. et al. Integration of telomere sequences with the draft human genome sequence. Nature 409, 948–951 (2001).
Linardopoulou, E. V. et al. Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication. Nature 437, 94–100 (2005).
Trask, B. et al. Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes. Hum. Mol. Genet. 7, 13–26 (1998).
Antonell, A., de Luis, O., Domingo-Roura, X. & Perez-Jurado, L. A. Evolutionary mechanisms shaping the genomic structure of the Williams–Beuren syndrome chromosomal region at human 7q11.23. Genome Res. 15, 1179–1188 (2005).
Bradley, M. E. & Benner, S. A. Phylogenomic approaches to common problems encountered in the analysis of low copy repeats: the sulfotransferase 1A gene family example. BMC Evol. Biol. 5, 22 (2005).
Jin, H. et al. Structural evolution of the BRCA1 genomic region in primates. Genomics 84, 1071–1082 (2004).
Koszul, R., Caburet, S., Dujon, B. & Fischer, G. Eucaryotic genome evolution through the spontaneous duplication of large chromosomal segments. EMBO J. 23, 234–243 (2004).
Schacherer, J., de Montigny, J., Welcker, A., Souciet, J. L. & Potier, S. Duplication processes in Saccharomyces cerevisiae haploid strains. Nucleic Acids Res. 33, 6319–6326 (2005).
Bailey, J. A., Liu, G. & Eichler, E. E. An Alu transposition model for the origin and expansion of human segmental duplications. Am. J. Hum. Genet. 73, 823–834 (2003).
Jurka, J., Kohany, O., Pavlicek, A., Kapitonov, V. V. & Jurka, M. V. Duplication, coclustering, and selection of human Alu retrotransposons. Proc. Natl Acad. Sci. USA 101, 1268–1272 (2004).
Zhou, Y. & Mishra, B. Quantifying the mechanisms for segmental duplications in mammalian genomes by statistical analysis and modeling. Proc. Natl Acad. Sci. USA 102, 4051–4056 (2005).
Babcock, M. et al. Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu-mediated recombination events during evolution. Genome Res. 13, 2519–2532 (2003).
Eichler, E. E., Archidiacono, N. & Rocchi, M. CAGGG repeats and the pericentromeric duplication of the hominoid genome. Genome Res. 9, 1048–1058 (1999).
Woodward, K. J. et al. Heterogeneous duplications in patients with Pelizaeus–Merzbacher disease suggest a mechanism of coupled homologous and nonhomologous recombination. Am. J. Hum. Genet. 77, 966–987 (2005).
Pentao, L., Wise, C., Chinault, A., Patel, P. & Lupski, J. Charcot–Marie–Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1. 5 Mb monomer unit. Nature Genet. 2, 292–300 (1992).
Shaw, C. J. & Lupski, J. R. Implications of human genome architecture for rearrangement-based disorders: the genomic basis of disease. Hum. Mol. Genet. 13, R57–R64 (2004).
Stankiewicz, P. & Lupski, J. R. Genome architecture, rearrangements and genomic disorders. Trends Genet. 18, 74–82 (2002).
Reiter, L. T. et al. Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients. Am. J. Hum. Genet. 62, 1023–1033 (1998).
Lopez-Correa, C. et al. Recombination hotspot in NF1 microdeletion patients. Hum. Mol. Genet. 10, 1387–1392 (2001).
Bi, W. et al. Reciprocal crossovers and a positional preference for strand exchange in recombination events resulting in deletion or duplication of chromosome 17p11.2. Am. J. Hum. Genet. 73, 1302–1315 (2003).
Fredman, D. et al. Complex SNP-related sequence variation in segmental genome duplications. Nature Genet. 36, 861–866 (2004).
Sebat, J. et al. Large-scale copy number polymorphism in the human genome. Science 305, 525–528 (2004).
Iafrate, A. J. et al. Detection of large-scale variation in the human genome. Nature Genet. 36, 949–951 (2004).
Tuzun, E. et al. Fine-scale structural variation of the human genome. Nature Genet. 37, 727–732 (2005).
Sharp, A. J. et al. Segmental duplications and copy-number variation in the human genome. Am. J. Hum. Genet. 77, 78–88 (2005).
Tayebi, N. et al. Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Mol. Genet. Metab. 79, 104–109 (2003).
Pavlicek, A., House, R., Gentles, A. J., Jurka, J. & Morrow, B. E. Traffic of genetic information between segmental duplications flanking the typical 22q11.2 deletion in velo-cardio-facial syndrome/DiGeorge syndrome. Genome Res. 15, 1487–1495 (2005).
Verrelli, B. C. & Tishkoff, S. A. Signatures of selection and gene conversion associated with human color vision variation. Am. J. Hum. Genet. 75, 363–375 (2004).
Bosch, E., Hurles, M. E., Navarro, A. & Jobling, M. A. Dynamics of a human interparalog gene conversion hotspot. Genome Res. 14, 835–844 (2004).
Hurles, M. E., Willey, D., Matthews, L. & Hussain, S. S. Origins of chromosomal rearrangement hotspots in the human genome: evidence from the AZFa deletion hotspots. Genome Biol. 5, R55 (2004).
Jeffreys, A. J. & May, C. A. Intense and highly localized gene conversion activity in human meiotic crossover hot spots. Nature Genet. 36, 151–156 (2004).
Jeffreys, A. J. & Neumann, R. Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot. Hum. Mol. Genet. 14, 2277–2287 (2005).
Jackson, M. S. et al. Evidence for widespread reticulate evolution within human duplicons. Am. J. Hum. Genet. 77, 824–840 (2005).
Estivill, X. et al. Chromosomal regions containing high-density and ambiguously mapped putative single nucleotide polymorphisms (SNPs) correlate with segmental duplications in the human genome. Hum. Mol. Genet. 11, 1987–1995 (2002).
Hallast, P., Nagirnaja, L., Margus, T. & Laan, M. Segmental duplications and gene conversion: human luteinizing hormone/chorionic gonadotropin β gene cluster. Genome Res. 15, 1535–1546 (2005).
Rozen, S. et al. Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature 423, 873–876 (2003).
Gonzalez, I. L. et al. Variation among human 28S ribosomal RNA genes. Proc. Natl Acad. Sci. USA 82, 7666–7670 (1985).
Reiter, L. et al. A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nature Genet. 12, 288–297 (1996).
Bayes, M., Magano, L. F., Rivera, N., Flores, R. & Perez Jurado, L. A. Mutational mechanisms of Williams–Beuren syndrome deletions. Am. J. Hum. Genet. 73, 131–151 (2003).
Visser, R. et al. Identification of a 3.0-kb major recombination hotspot in patients with sotos syndrome who carry a common 1.9-Mb microdeletion. Am. J. Hum. Genet. 76, 52–67 (2005).
Nadeau, J. H. & Taylor, B. A. Lengths of chromosomal segments conserved since divergence of man and mouse. Proc. Natl Acad. Sci. USA 81, 814–818 (1984).
Pevzner, P. & Tesler, G. Genome rearrangements in mammalian evolution: lessons from human and mouse genomes. Genome Res. 13, 37–45 (2003).
Kent, W. J., Baertsch, R., Hinrichs, A., Miller, W. & Haussler, D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc. Natl Acad. Sci. USA 100, 11484–11489 (2003).
Pevzner, P. & Tesler, G. Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution. Proc. Natl Acad. Sci. USA 100, 7672–7677 (2003).
Bourque, G., Pevzner, P. A. & Tesler, G. Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes. Genome Res. 14, 507–516 (2004).
Armengol, L., Pujana, M. A., Cheung, J., Scherer, S. W. & Estivill, X. Enrichment of segmental duplications in regions of breaks of synteny between the human and mouse genomes suggest their involvement in evolutionary rearrangements. Hum. Mol. Genet. 12, 2201–2208 (2003).
Bailey, J. A., Baertsch, R., Kent, W. J., Haussler, D. & Eichler, E. E. Hotspots of mammalian chromosomal evolution. Genome Biol. 5, R23 (2004).
Armengol, L. et al. Murine segmental duplications are hot spots for chromosome and gene evolution. Genomics 86, 692–700 (2005).
Murphy, W. J. et al. Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps. Science 309, 613–617 (2005).
Yunis, J. J. & Prakash, O. The origin of man: a chromosomal pictorial legacy. Science 215, 1525–1530 (1982).
Yunis, J. J., Sawyer, J. R. & Dunham, K. The striking resemblance of high-resolution G-banded chromosomes of man and chimpanzee. Science 208, 1145–1148 (1980).
Fan, Y., Linardopoulou, E., Friedman, C., Williams, E. & Trask, B. J. Genomic structure and evolution of the ancestral chromosome fusion site in 2q13–2q14.1 and paralogous regions on other human chromosomes. Genome Res. 12, 1651–1662 (2002).
Yue, Y. et al. Genomic structure and paralogous regions of the inversion breakpoint occurring between human chromosome 3p12.3 and orangutan chromosome 2. Cytogenet. Genome Res. 108, 98–105 (2005).
Kehrer-Sawatzki, H. et al. Breakpoint analysis of the pericentric inversion distinguishing human chromosome 4 from the homologous chromosome in the chimpanzee (Pan troglodytes). Hum. Mutat. 25, 45–55 (2005).
Szamalek, J. M. et al. Molecular characterisation of the pericentric inversion that distinguishes human chromosome 5 from the homologous chimpanzee chromosome. Hum. Genet. 117, 168–176 (2005).
Kehrer-Sawatzki, H., Szamalek, J. M., Tanzer, S., Platzer, M. & Hameister, H. Molecular characterization of the pericentric inversion of chimpanzee chromosome 11 homologous to human chromosome 9. Genomics 85, 542–550 (2005).
Locke, D. P. et al. Refinement of a chimpanzee pericentric inversion breakpoint to a segmental duplication cluster. Genome Biol. 4, R50 (2003).
Kehrer-Sawatzki, H., Sandig, C. A., Goidts, V. & Hameister, H. Breakpoint analysis of the pericentric inversion between chimpanzee chromosome 10 and the homologous chromosome 12 in humans. Cytogenet. Genome Res. 108, 91–97 (2005).
Shimada, M. K. et al. Nucleotide sequence comparison of a chromosome rearrangement on human chromosome 12 and the corresponding ape chromosomes. Cytogenet. Genome Res. 108, 83–90 (2005).
Goidts, V. et al. Independent intrachromosomal recombination events underlie the pericentric inversions of chimpanzee and gorilla chromosomes homologous to human chromosome 16. Genome Res. 15, 1232–1242 (2005).
Kehrer-Sawatzki, H. et al. Molecular characterization of the pericentric inversion that causes differences between chimpanzee chromosome 19 and human chromosome 17. Am. J. Hum. Genet. 71, 375–388 (2002).
Dennehey, B. K., Gutches, D. G., McConkey, E. H. & Krauter, K. S. Inversion, duplication, and changes in gene context are associated with human chromosome 18 evolution. Genomics 83, 493–501 (2004).
Muller, S., Hollatz, M. & Wienberg, J. Chromosomal phylogeny and evolution of gibbons (Hylobatidae). Hum. Genet. 113, 493–501 (2003).
Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005).
Feuk, L. et al. Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies. PLoS Genet. 1, e56 (2005).
Fortna, A. et al. Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biol. 2, e207 (2004).
Muller, H. J. Bar duplication. Science 83, 528–530 (1936).
Ohno, S., Wolf, U. & Atkin, N. Evolution from fish to mammals by gene duplication. Hereditas 59, 169–187 (1968).
Taylor, J. S. & Raes, J. Duplication and divergence: the evolution of new genes and old ideas. Annu. Rev. Genet. 38, 615–643 (2004).
Brand-Arpon, V. et al. A genomic region encompassing a cluster of olfactory receptor genes and a myosin light chain kinase (MYLK) gene is duplicated on human chromosome regions 3q13–q21 and 3p13. Genomics 56, 98–110 (1999).
Wong, A. C. et al. Two novel human RAB genes with near identical sequence each map to a telomere-associated region: the subtelomeric region of 22q13.3 and the ancestral telomere band 2q13. Genomics 59, 326–334 (1999).
Wong, A. et al. Diverse fates of paralogs following segmental duplication of telomeric genes. Genomics 84, 239–247 (2004).
Mudge, J. M. & Jackson, M. S. Evolutionary implications of pericentromeric gene expression in humans. Cytogenet. Genome Res. 108, 47–57 (2005).
Grunau, C. et al. Frequent DNA hypomethylation of human juxtacentromeric BAGE loci in cancer. Genes Chromosomes Cancer 43, 11–24 (2005).
Hollox, E. J., Armour, J. A. & Barber, J. C. Extensive normal copy number variation of a β-defensin antimicrobial-gene cluster. Am. J. Hum. Genet. 73, 591–600 (2003).
Khaitovich, P. et al. Regional patterns of gene expression in human and chimpanzee brains. Genome Res. 14, 1462–1473 (2004).
Birtle, Z., Goodstadt, L. & Ponting, C. Duplication and positive selection among hominin-specific PRAME genes. BMC Genomics 6, 120 (2005).
Semple, C. A., Rolfe, M. & Dorin, J. R. Duplication and selection in the evolution of primate β-defensin genes. Genome Biol. 4, R31 (2003).
Feuk, L., Carson, A. R. & Scherer, S. W. Structural variation in the human genome. Nature Rev. Genet. 7, 85–97 (2006).
Eichler, E. E. Widening the spectrum of human genetic variation. Nature Genet. 38, 9–11 (2006).
Perry, G. H. et al. Hotspots for copy number variation in chimpanzees and humans. Proc. Natl Acad. Sci. USA 103, 8006–8011 (2006).
Wilson, E. B. The sex chromosomes. Arch. Mikrosk. Anat. Entwicklungsmech. 77, 249–271 (1911).
Levine, P., Katzin, E. M. & Burnham, L. Isoimmunizationin pregnancy: its possible bearing on the etiology of erythroblastosis foetalis. JAMA 116, 825–827 (1941).
Cooley, T. B. & Lee, P. A series of cases of splenomegaly inchildren with anemia and peculiar bone changes. Trans. Am. Pediatr. Soc. 37, 29 (1925).
Fucharoen, S. & Winichagoon, P. Thalassemia and abnormal hemoglobin. Int. J. Hematol. 76 (Suppl. 2), 83–89 (2002).
Wagner, F. F. & Flegel, W. A. Review: the molecular basis of the Rh blood group phenotypes. Immunohematol. 20, 23–36 (2004).
Deeb, S. S. The molecular basis of variation in human color vision. Clin. Genet. 67, 369–377 (2005).
Lupski, J. R. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 14, 417–422 (1998).
Stefansson, H. et al. A common inversion under selection in Europeans. Nature Genet 37, 129–137 (2005).
Gonzalez, E. et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307, 1434–1440 (2005).
Aitman, T. J. et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 439, 851–855 (2006).
Kleinjan, D. A. & van Heyningen, V. Long-range control of gene expression: emerging mechanisms and disruption in disease. Am. J. Hum. Genet. 76, 8–32 (2005).
Lee, J. A. et al. Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1 position effect. Ann. Neurol. 59, 398–403 (2006).
Velagaleti, G. V. et al. Position effects due to chromosome breakpoints that map approximately 900 kb upstream and approximately 1.3 Mb downstream of SOX9 in two patients with campomelic dysplasia. Am. J. Hum. Genet. 76, 652–662 (2005).
Paulding, C. A., Ruvolo, M. & Haber, D. A. The Tre2 (USP6) oncogene is a hominoid-specific gene. Proc. Natl Acad. Sci. USA 100, 2507–2511 (2003).
Zody, M. C. et al. Analysis of the DNA sequence and duplication history of human chromosome 15. Nature 440, 671–675 (2006).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Related links
Glossary
- Low copy repeat
-
A term with variable meaning that is sometimes used synonymously with segmental duplication. It can denote a group of juxtaposed duplicons (duplication block), individual segmental duplication events or individual duplicons. The term emphasizes the low copy number of repeats (2–50 copies) relative to most transposable elements.
- Gene conversion
-
Used here in the general sense as the transfer of genetic information from one sequence to another based on homology — the strict definition is non-reciprocal meiotic exchange resulting in products with a 3:1 ratio of alleles.
- Molecular clock
-
A molecular clock is said to exist when the rate of nucleotide change is approximately constant over evolutionary time; this rate can then be used to estimate the age of duplication or speciation events.
- Whole-genome shotgun sequencing
-
A sequencing strategy that involves random fragmentation of the entire genome. The fragments are sequenced, and highly refined algorithms are used to reassemble the original genomic DNA sequence.
- Fluorescence in situ hybridization
-
A technique in which a fluorescently labelled DNA probe is used to detect a particular chromosome region or gene by fluorescence microscopy. The intensity of the signal can be used to detect copy-number differences between the labelled chromosomal regions.
- Hominoid
-
A primate superfamily that includes the great apes (orangutans, gorillas, chimpanzees and bonobos) and humans(hominids).
- Effective ancestral population size
-
Approximately the number of breeding individuals that produce offspring that live to reproductive age. It influences the rate of loss of genetic variation, the efficiency of natural selection and the accumulation of beneficial and deleterious mutations. It is frequently much smaller than the number of individuals in a population.
- Pericentromeric region
-
The sequence adjacent to the centromere that is often defined as the first chromosomal sub-band or by defined physical distances of 2–5 Mb from the higher-order α-satellite arrays that comprise the centromere.
- Interstitial region
-
An arbitrary name given to the euchromatic sequence within a chromosome arm that is bounded by the pericentromeric and subtelomeric regions.
- Duplicon
-
A duplication, or portion thereof, that is traceable to an ancestral or donor location; a secondary duplication event can be composed of multiple duplicons. Also sometimes referred to as a low copy repeat.
- Microrearrangements
-
Rearrangements that are less than a megabase in size.
- Non-allelic homologous recombination
-
Homologous recombination between paralogous sequence (for example, segmental duplication and repetitive sequence); a major mechanism of recurrent rearrangements, also known as unequal crossing-over.
- Immunoglobulin heavy-chain class-switch recombination
-
Non-homologous recombination that occurs during the development of B lymphocytes to produce difference classes (isotypes) of heavy-chain molecule.
- α-Satellite
-
A class of ∼170 bp repetitive sequences that are found at the centromeres of most primates. They are present in tandem arrays that constitute megabases of sequence.
- Genomic disorder
-
A disease that results from the gain, loss or alteration of dosage-sensitive gene(s) as a result of genomic rearrangement (such as duplication, deletion and inversion).
- Recombination hot spots
-
Regions of sequence that undergo increased meiotic rates of recombination.
- Single nucleotide polymorphism
-
(SNP). A single nucleotide difference between orthologous sites. A strict definition requires a population frequency of at least 1% for the rare allele. SNPs represents 90% of the genetic variation within the human population in terms of numbers of variants.
- Paralogous sequence variant
-
A single nucleotide difference between copies of a segmental duplication (or any paralogous sequence), which can be variant or fixed in a population.
- Complete hydatidiform mole
-
Placental mass with uncontrolled growth due to the fertilization of an enucleated egg with one (90%) or two (10%) sperm — useful for genetic studies as those derived from single sperm represent a haploid genome.
- Chromosome painting
-
Visualization of individual, whole chromosomes by fluorescence in situ hybridization.
- Synteny
-
A term originally meaning simply 'on the same chromosome' (regardless of linkage) which has now been co-opted to refer to a continuous block of sequence with a shared organization (conserved linkage) between two or more species.
- Exaptation
-
When a gene or part of a gene (such as a domain or exon) is used for a new potentially adaptive function. Can also be used to describe cases where splicing occurs in non-genic sequence to create a new exon. This is a type of domain accretion, which is the addition of an exon or exons to a gene or transcript.
- Duplication block
-
A group of juxtaposed duplicons that might be duplicated as part of a larger secondary duplication. Also sometimes referred to as a low copy repeat.
- Duplication core
-
The central sequence around which a complex pattern of duplication forms common to a subset of interspersed duplications.
- Xenobiotic
-
A compound that is foreign to biological systems, often referring to man-made compounds that are resistant to biodegradation.
Rights and permissions
About this article
Cite this article
Bailey, J., Eichler, E. Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet 7, 552–564 (2006). https://doi.org/10.1038/nrg1895
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrg1895
