The Variable Rotation Period of the Inner Region of Saturn's Plasma Disk D. A. Gurnett, et al. Science 316, 442 (2007); DOI: 10.1126/science.1138562

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netometer (MAG) instruments on the Cassini The Variable Rotation Period spacecraft, which is in orbit around Saturn. In an earlier study (16) using electron density mea- of the Inner Region of Saturn’s surements from the RPWS, we noticed that in the vicinity of Enceladus’ orbit, from about 3 to 5 RS, the electron density is often quite different on the Plasma Disk inbound and outbound portions of the same pass D. A. Gurnett,1 A. M. Persoon,1 W. S. Kurth,1 J. B. Groene,1 T. F. Averkamp,1 (Fig. 1). This variability was initially thought to M. K. Dougherty,2 D. J. Southwood2,3 be attributable to the spacecraft position relative to Enceladus, but further study showed that it was We show that the plasma and magnetic fields in the inner region of Saturn’s plasma disk rotate not so. Instead, using the time-variable SKR in synchronism with the time-variable modulation period of Saturn’s kilometric radio emission. longitude system introduced by Kurth et al.(17), This relation suggests that the radio modulation has its origins in the inner region of the plasma we found (Fig. 2) that the electron density in the disk, most likely from a centrifugally driven convective instability and an associated plasma outflow inner region of the plasma disk has a nearly that slowly slips in phase relative to Saturn’s internal rotation. The slippage rate is determined sinusoidal variation with SKR longitude and by the electrodynamic coupling of the plasma disk to Saturn and by the drag force exerted by its that this variation is in phase with a similar interaction with the Enceladus neutral gas torus. nearly sinusoidal variation in the azimuthal, Bϕ, component of the magnetic field in the ecause Saturn is a giant gaseous planet, magnetosphere from near the outer edge of the plasma disk. This relation strongly suggests its internal rotation period cannot be Aring(11, 12). The co-rotation is caused by that the plasma density and magnetic field in Baccurately determined from visual obser- electromagnetic forces imposed by currents that the inner region of the plasma disk have a vations. Although it has been long accepted that flow along the highly conducting magnetic field rotational control that is directly linked to the the magnetic dipole axis of Saturn is aligned lines between the plasma disk and the upper time-variable period of the SKR modulation. almost exactly with its rotational axis (1, 2), atmosphere of Saturn. Most of the plasma in the By itself, a sinusoidal longitude variation does various magnetospheric phenomena display ro- plasma disk is believed to originate from not provide proof of rotational control, even tational modulation effects near its nominal ionization of a torus of neutral gas that is present though the longitude is measured relative to a 3–5 rotation period ( ). Of these, the most near the orbit of Enceladus. This torus originates rotating reference. To demonstrate rotational on October 20, 2008 thoroughly studied is Saturn kilometric radiation from geyserlike plumes of water on Enceladus control, it is essential that measurements be made (SKR), which is an intense radio emission that inject water vapor and ice particles into orbit over a range of local times in order to confirm that discovered during the 1980–1981 Voyager flybys around Saturn (13–15). Because of the rapid the longitude is the controlling variable. Fortu- of Saturn (3). The SKR modulation period was rotation of the plasma disk, the centrifugal force nately, the orbit of Cassini provides good local- determined by Voyager to be 10 hours, 39 min, at these radial distances is substantially larger time coverage and longitude coverage of both the 24 ± 7s (6). This value is now the internationally than Saturn’s gravitational force. Interchange magnetic field and the electron density (figs. S1 accepted rotation period of Saturn (7). More motions driven by the centrifugal force then act andS2).Asimpletestcanthenbeperformedto recently, radio measurements from the Ulysses to transport the plasma outward into the magne- confirm rotational control. This test consists of 8–10

and Cassini spacecraft ( ) have shown that tosphere. Because the plasma particles are con- plotting the measured quantities as a function of www.sciencemag.org the SKR modulation period varies by as much as strained by electromagnetic forces to move the longitude relative to some fixed direction, such 1% on time scales of years. Because of its large approximately along magnetic field lines, the as the Sun. This test shows that the amplitude of inertia, the internal rotation period cannot possi- centrifugal force also acts to concentrate the the modulation decreases and the spread of the bly have changed by such a large amount. How plasma near the equatorial plane, thereby forming data points relative to the best fit increases then is the SKR period related to the rotation the disklike structure. significantly (compare Fig. 2, B and C, with fig. period of the interior of Saturn? In this paper we ThedatausedinthisstudyarefromtheRadio S4, B and C), thereby providing convincing show that the SKR modulation is directly linked and Plasma Wave Science (RPWS) and Mag- evidence that both the magnetic field and the

to the rotational modulation of plasma and Downloaded from magnetic fields in the inner region of Saturn’s Fig. 1. The electron density plasma disk, near the moon Enceladus, which ne obtained from Cassini orbits Saturn at 3.95 Saturn radii (RS)(1Saturn RPWS upper hybrid reso- radius = 60,268 km). We propose that the nance measurements (20) rotational modulation is caused by a centrifugally for 14 equatorial orbits from driven two-cell convective instability in the plas- 1 July 2004 to 1 July 2006. ma disk that originates from its interaction with Thedashedlineisapower- the neutral gas torus produced by Enceladus. law fit to the region beyond R k 4 −3 This instability causes a rotating plasma outflow 5 S,and =5.5×10 cm R 4.14 is the constant in the that imposes rotational control on other processes S power law. Only equatorial farther out in the magnetosphere, such as the orbits with a north-south dis- generation of SKR. tance z from the equatorial Saturn’s plasma disk, sometimes also called plane less than 0.1 RS were the plasma sheet or plasmasphere, is a dense co- used in this study. There are rotating plasma with a north-south thickness of large variations from the R about 1 to 2 S that extends outward into the power-law fit in the region from 3 to 5 RS. By following the colored line for a given 1Department of Physics and Astronomy, University of Iowa, Iowa City, IA 52242, USA. 2Blackett Laboratory, Imperial orbit, one can see that the electron densities for the inbound and outbound portions of the same pass College, London SW7 2AZ, UK. 3European Space Agency, are often quite different. This hysteresis-like dependence on radial distance strongly suggests a 75738 Paris, France. longitudinal control.

442 20 APRIL 2007 VOL 316 SCIENCE www.sciencemag.org REPORTS plasma density in the inner region of the plasma discovered rotational density modulation in the the plasma disk to the planet. Because the ejection disk rotate at a rate that is synchronous with the inner region of the plasma disk acts as the cam that of mass from Enceladus probably has long-term time-variable SKR modulation. For other factors drives other rotationally modulated effects farther variations that affect the density of the neutral gas that could affect this interpretation, such as aliasing out in the magnetosphere. The main questions that torus, this model provides a ready explanation for due to data gaps, and for an analysis of the slow remain are how are these rotational effects the somewhat irregular long-term variations in the long-term time variations in the rotation rate, see produced in the inner region of the magnetosphere, SKR modulation period (9). It is already known the supporting onlinematerial(SOM). and how does the rotation rate relate to the internal that the Enceladus neutral gas torus has variations The occurrence of a large rotational modulation rotation of Saturn? on time scales of months (20), so variations on of the plasma and magnetic fields deep in the inner Because there is presently no accepted mech- much longer time scales are highly likely. Another region of the magnetosphere that is phase-locked anism for imposing a time-variable rotation rate possible long-term effect that could cause changes to the time-variable SKR modulation is surprising. from a source internal to Saturn, we proceed by in the rotation rate of the plasma disk is the Most of the rotational effects that have previously exploring the possibility that the time variability seasonal variation of the solar inclination angle, been reported occur much farther out in the mag- arises entirely within the plasma disk. It is already which affects the conductivity of the upper netosphere. That the density modulation occurs widely accepted (18, 19) that the rotation of the atmosphere and thereby the coupling to the planet. near the orbit of Enceladus strongly suggests that plasma disk is due to forces produced by field- To proceed further, we must next explain how the rotational effects observed farther out in the aligned currents that link the plasma disk to Saturn the density modulation is produced in the inner magnetosphere are driven by some rotational pro- (Fig. 3A). A very natural explanation for the time- region of the plasma disk. A possible model is cess that involves an interaction with the Enceladus variable rotation rate is then that the plasma disk motivated by the two-cell convection mechanism neutral gas torus. This conclusion is consistent slips at a time-variable rate relative to the upper suggested by Dessler et al.(21), which was with the view that the general direction of energy atmosphere of Saturn, which is where the coupling originally proposed to explain rotational effects flow should be outward, away from the source of to the planet takes place. The mechanism for in the magnetosphere of Jupiter and was also the plasma and in the direction of the centrifugal driving this slippage could then be ionization and suggested to apply to Saturn by Hill et al.(22). In force. In fact, this direction for the propagation of charge exchange in the neutral gas torus, both of our adaptation of this model (Fig. 3B), the two- rotational disturbances has already been suggested which produce a drag force that opposes the cell convection pattern has its origin as a and is the basis for the “camshaft” model proposed rotation of the plasma disk. This process is called centrifugally driven instability in the plasma disk by Espinosa et al.(4). In this model, an unspecified mass loading (19). In this model, the slippage rate (23) near the orbit of Enceladus. Such convective “ ” dm dt m t rotating disturbance, the cam, as in the camshaft is determined by the rate / ( ,mass; , time) instabilities are well known in laboratory plasma on October 20, 2008 of an engine, produces plasma and magnetic field atwhichmassispickedupbytheplasmadisk,and machines. As the plasma flows around the disturbances that propagate outward into the by the conductivity of the upper atmosphere, convection cycle (indicated by the closed stream- magnetosphere. Here we propose that the newly which controls the field-aligned currents that link lines in Fig. 3B), it picks up newly ionized plasma as it passes through the neutral gas torus (along the path from a to b in Fig. 3B), thereby Fig. 2. (A) The normalized increasing the plasma density. It is this density SKR intensity as a function of increase that accounts for the longitudinal density the longitude of the Sun, variations observed in the inner region of the lSun, using the time-variable

plasma disk. The density increase also ensures www.sciencemag.org SKR longitude system intro- F nmw2R n duced by Kurth et al.(17). that the centrifugal force, c = ,where is m The longitude of the Sun is the plasma number density, is the molecular w R used in this plot because the mass, is the rotation rate, and is the radial F SKR modulation is known to distance, at point c(2)ishigherthanata F be a purely temporal varia- symmetrically located point c(1). It is this tion (29), like a flashing difference in the centrifugal forces that drives light, not a rotating beacon. the convection. From the ionization rate given by

The characteristic nearly si- Hansen et al.(24) for the neutral gas torus, 8.7 × Downloaded from nusoidal modulation of the 10−5 cm−3 s−1, we estimate that it takes about a SKR intensity is clearly ap- week to produce the observed ~50 cm−3 peak-to- parent. (B) The average azi- peak density variation as the plasma flows muthal Bϕ componentofthe through the neutral gas torus. magnetic field in the plasma Most previous models of centrifugally driven R disk (3 to 12 S)asafunc- convection suggest that the convective motions tion of the SKR longitude of should be dominated by high-order, m >> 1, l l the spacecraft SC. SC is azimuthal modes that evolve into fingerlike used because we anticipated azimuthal structures (25, 26). However, these that the magnetic field would models do not consider the process by which the have a rotational control, as plasma is produced. For an azimuthally symmet- has been assumed by other 4 ric plasma source, such as the Enceladus neutral authors ( ). As can be seen, m the magnetic field displays a gas torus, we believe that the lowest-order = very clear, nearly sinusoidal 1 (two-cell) mode should dominate, because this mode produces the longest path length through dependence on lSC.(C)The electron density as a function the source region, thereby giving the largest of lSC, where again we anticipated a possible rotational control. The radial distance range in this case density increase and the largest growth rate for has been limited to the inner region of the plasma disk (3 to 5 RS), because this is the region where the the instability. Because there is a continuous electron density variations are the largest (Fig. 1). A very clear, nearly sinusoidal modulation is evident, production of plasma from the torus, in a steady with an amplitude variation of nearly a factor of 2 and a phase at the peak (lSC ~ 330°) that is almost state there must be a corresponding outflow of the same as for the magnetic field. plasma from the plasma disk into the outer re-

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gions of the magnetosphere. The two-cell con- the outward-propagating disturbance from the be produced by the fact that the net dayside vection would then cause a concentration of the cam interacts with the morning side of the mag- conductivity of the southern hemisphere of Saturn outflowing plasma on the dense side of the netopause, see the SOM. is currently higher than in the northern hemi- convection pattern (Fig. 3B); that is, at an SKR A potentially important feature of the convec- sphere, not only because high southerly latitudes longitude of lSC ~ 330°. As the convection tion pattern that needs to be explained is the close are currently in sunlight but also because the rings pattern rotates, this outflow would produce relation between the phase of the azimuthal are partially shadowing the northern hemisphere. perturbations that propagate far out into the magnetic field and the phase of plasma density This north-south difference in the illumination magnetosphere, thereby acting as the cam that modulation (Fig. 2, B and C). This relation is most greatly increases the conductivity of the upper drives other rotationally modulated magneto- likely related to the azimuthal torque required to atmosphere in the southern hemisphere relative to spheric effects, such as the SKR. From the oppose the change in the angular momentum of that in the northern hemisphere. The immediate Voyager 1 and 2 radio observations (27), it is the plasma disk caused by the mass loading. consequence of this difference is that interchange known that SKR is generated at relatively low Because both ionization and charge exchange are motion would be resisted more by the southern altitudes along magnetic field lines that pass near proportional to the plasma density, they both ionosphere (23). In the high-density sector where the magnetopause on the late-morning side of the contribute to the mass loading. The current system flux tubes would move out, the northern iono- magnetosphere. As the perturbations from lSC ~ that produces this torque and the resulting sphere has to transmit a poleward motion to the 330° propagate outward, the associated magnetic contribution to the Bϕ magnetic field are then southern ionosphere and vice versa in the inward- field perturbations (fig. S3) develop a phase lag expected to be largest in the region of highest moving sector. This asymmetry would require a of about 149° to 195° by the time they reach the plasma density, which would explain why these significant transverse magnetic field component at vicinity of the magnetopause at R ~20RS.This two quantities are in phase. However, the relation the equator. A quarter-cycle lag is expected phase lag, which has been previously studied by between the magnetic field and the plasma density between outward motion and the peak bending Espinosa et al.(4)andCowleyet al.(28), is variations may be more subtle. If the current inward of the field (that is, a peak negative value almost exactly the right amount to explain the systems linking the plasma sheet to the northern of the radial field perturbation, DBr). Recalling the generation of SKR in the late morning at a local and southern hemispheres are identical, then there phase relation originally identified by Espinosa time of about 8 to 11 hours and a subsolar SKR would be no Bϕ magnetic field component at the et al.(4) (that DBr leads Bϕ), one sees that the longitude of lSun = 100°. For a further discus- equator. The equatorial Bϕ component would then observed phase relation between Bϕ and ne (ne, sion of the geometry involved and for com- have to be due to an asymmetry between northern electron density) is consistent.

ments on how the SKR might be generated as and southern hemispheres. The asymmetry could Because our model is based on a centrifugally on October 20, 2008 driven instability in the plasma disk that acts as a Fig. 3. (A), adapted from camshaft, it does not necessarily require a 18 Hill ( ), shows the mecha- rotating magnetic anomaly or any other rotating nism by which the plasma source internal to Saturn. Therefore, the internal disk is coupled to the upper rotation period of Saturn cannot be determined atmosphere of Saturn via from the period of the SKR modulation. The only magnetic field–aligned cur- conclusion that can be drawn is that the internal rents, J∥. The field-aligned rotation period must be less than the shortest currents transfer angular

momentum from the planet SKR modulation period ever observed, which www.sciencemag.org to the plasma disk via the currently is slightly less than the period observed by Voyager (9). If some internal source with the J⊥ Â B force exerted, where J⊥ is the component of correct time-variable rotation rate were to be current flowing perpendicu- eventually identified, it is clear that any new lar to the magnetic field B. explanation would need to account for the ro- This force opposes the drag tating plasma density and magnetic fields re- force exerted on the disk as ported in this paper, as well as their linkage to the

mass produced by ionization time-variable SKR modulation rate. Downloaded from and charge exchange from the Enceladus gas torus is References and Notes picked up by the rapidly 1. E. J. Smith et al., Science 207, 407 (1980). rotating magnetic field. This 2. J. E. P. Connerney, L. Davis Jr., D. L. Chenette, in Saturn, drag force causes the plas- T. Gehrels, M. S. Matthews, Eds. (Univ. of Arizona Press, ma disk, which rotates at an Tucson, AZ, 1984), pp. 354–377. angular rate w,toslipslowly 3. J. W. Warwick et al., Science 212, 239 (1981). 4. S. A. Espinosa, D. J. Southwood, M. K. Dougherty, with respect to the rotation J. Geophys. Res. W 108, 1086 (2003). rate of the upper atmo- 5. G. Giampieri, M. K. Dougherty, E. J. Smith, C. T. Russell, sphere of Saturn. (B)The Nature 441, 62 (2006). rotating two-cell plasma con- 6. M. D. Desch, M. L. Kaiser, Geophys. Res. Lett. 8, 253 vection pattern that we propose to explain the longitudinal modulation of the plasma density and (1981). magnetic field in the inner region of the plasma disk. In this model, the two-cell convection pattern, 7. M. E. Davies et al., Cel. Mech. Dyn. Astron. 63, 127 (1996). 8. A. Lecacheux, P. Galopeau, M. Aubier, Planetary Radio shown as viewed from the north pole of Saturn, is driven by a centrifugal instability that arises from Emissions IV, H. O. Rucker, S. J. Bauer, A. Lecacheux, Eds. ionization of the neutral gas torus. As the plasma flows through the neutral gas torus from a to b, the (Austrian Academy of Sciences Press, Vienna, 1997). 2 density increases because of this ionization, causing the centrifugal force Fc = nmw R at Fc(2) to be 9. P. H. M. Galopeau, A. Lecacheux, J. Geophys. Res. 105, greater than at the symmetrical point Fc(1) on the opposite side of the convection pattern. It is this 13089 (2000). difference in the centrifugal forces that drives the convection. A radial outflow of plasma in the “heavy” 10. D. A. Gurnett et al., Science 307, 1255 (2005). et al. Science sector of the convection pattern then acts as the cam (4) that drives the rotational modulation of various 11. D. T. Young , 307, 1262 (2005). 12. H. S. Bridge et al., Science 212, 217 (1981). phenomena in the outer magnetosphere, such as the SKR. The slippage rate, and therefore the SKR 13. C. C. Porco et al., Science 311, 1393 (2006). modulation period, are determined by the mass loading rate dm/dt from the neutral gas torus and by the 14. M. K. Dougherty et al., Science 311, 1406 (2006). coupling to the upper atmosphere, both of which are likely to have long-term variations. 15. J. H. Waite Jr. et al., Science 311, 1419 (2006).

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16. A. M. Persoon et al., Geophys. Res. Lett. 32, L23105 (2005). 24. K. C. Hansen et al., Geophys. Res. Lett. 32, L20S06 30. The research at the University of Iowa was supported 17. W. S. Kurth, A. Lecacheux, T. F. Averkamp, J. B. Groene, (2005). by NASA through contract 1279973 with the Jet D. A. Gurnett, Geophys. Res. Lett. 34, L02201 (2007). 25. G. L. Siscoe, D. Summers, J. Geophys. Res. 86, 8471 Propulsion Laboratory. 18. T. W. Hill, J. Geophys. Res. 84, 6554 (1979). (1981). Supporting Online Material 19. A. Eviatar, R. L. McNutt Jr., G. L. Siscoe, J. D. Sullivan, 26. Y. S. Yang, R. A. Wolf, R. W. Spiro, T. W. Hill, A. J. www.sciencemag.org/cgi/content/full/1138562/DC1 J. Geophys. Res. J. Geophys. Res. 88, 823 (1983). Dessler, 99, 8755 (1994). SOM Text et al. Science J. Geophys. Res. – 20. L. W. Esposito , 307, 1251 (2005). 27. P. Zarka, 103, 20, 159 20, 194 Figs. S1 to S8 Planet. Space Sci. 21. A. J. Dessler, R. R. Sandel, S. K. Atreya, (1998). References 29, 215 (1981). 28. S. W. H. Cowley et al., Geophys. Res. Lett. 33, L07104 22. T. W. Hill, A. J. Dessler, L. J. Maher, J. Geophys. Res. 86, (2006). 7 December 2006; accepted 7 March 2007 9020 (1981). 29. M. L. Kaiser et al.,inSaturn, T. Gehrels, M. S. Matthews, Published online 22 March 2007; 23. D. J. Southwood, M. G. Kivelson, J. Geophys. Res. 94, 299 Eds. (Univ. of Arizona Press, Tucson, AZ, 1984), 10.1126/science.1138562 (1989). pp. 378–415. Include this information when citing this paper.

ASD was needed. We have performed high- resolution genomic microarray analysis on a Strong Association of De Novo Copy sample of 264 families to determine the rate of de novo copy number mutation in unaffected and Number Mutations with Autism affected children. Our study focused on a sample of 264 fami- Jonathan Sebat,1* B. Lakshmi,1 Dheeraj Malhotra,1* Jennifer Troge,1* Christa Lese-Martin,2 lies, including 118 “simplex” families contain- Tom Walsh,3 Boris Yamrom,1 Seungtai Yoon,1 Alex Krasnitz,1 Jude Kendall,1 Anthony Leotta,1 ing a single child with autism, 47 “multiplex” Deepa Pai,1 Ray Zhang,1 Yoon-Ha Lee,1 James Hicks,1 Sarah J. Spence,4 Annette T. Lee,5 families with multiple affected siblings, and 99 Kaija Puura,6 Terho Lehtimäki,7 David Ledbetter,2 Peter K. Gregersen,5 Joel Bregman,8 control families with no diagnoses of autism. James S. Sutcliffe,9 Vaidehi Jobanputra,10 Wendy Chung,10 Dorothy Warburton,10 The majority of patients came from the Autism Mary-Claire King,3 David Skuse,11 Daniel H. Geschwind,12 T. Conrad Gilliam,13 Genetic Resource Exchange (AGRE) and from Kenny Ye,14 Michael Wigler1† the National Institute of Mental Health (NIMH) Center for Collaborative Genetic Studies of on October 20, 2008 We tested the hypothesis that de novo copy number variation (CNV) is associated with autism Mental Disorders. Additional families were ob- spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the tained through the authors (T.C.G., J.S.S., J.B., genomic DNA of patients and unaffected subjects to detect copy number variants not present in and D.S). Efforts were made at all of the col- their respective parents. Candidate genomic regions were validated by higher-resolution CGH, lecting sites to exclude cases of syndromic paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. autism (i.e., those with severe mental retarda- Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were tion or other congenital anomalies) and to identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients exclude known cytogenetic abnormalities. with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs Identities of all subjects and their parents were coded so that analysis could be done blind to were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous www.sciencemag.org and included mutations of single genes. These findings establish de novo germline mutation as a affected status while maintaining knowledge of more significant risk factor for ASD than previously recognized. 1Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. 2Department of Human 5 Genetics, Emory University School of Medicine, Atlanta, GA utism spectrum disorders (ASDs) [Men- sclerosis ( ), mutations in a single gene have 30322, USA. 3Department of Medicine and Genome delian Inheritance in Man (MIM) 209850] been identified. Otherwise, neither linkage nor Sciences, University of Washington, Seattle, WA 98195– Aare characterized by language impair- cytogenetics has unambiguously identified spe- 7720, USA. 4Pediatrics and Neurodevelopmental Psychiatry Branch, National Institute of Mental Health, National ments, social deficits, and repetitive behaviors. cific genes involved. Downloaded from Institutes of Health, Bethesda, MD 20892–1255, USA. The onset of symptoms occurs by the age of 3 and Genetic heterogeneity poses a considerable 5Feinstein Institute for Medical Research, North Shore–Long usually requires extensive support for the lifetime challenge to traditional approaches for gene Island Jewish Health System, Manhasset, NY 11030, USA. of the afflicted. The prevalence of ASD is es- mapping (6). Some of these limitations are 6Department of Child Psychiatry, University of Tampere, 7 timatedtobe1in166(1), making it a major overcome by methods that rely on the direct Medical School, Tampere, Finland. Department of Clinical Chemistry, University Hospital of Tampere and University of burden to society. detection of functional variants, which in most Tampere, Medical School, Tampere, Finland. 8Fay J. Lindner Genetics plays a major role in the etiology of cases are de novo events. New array-based Center for Autism and Developmental Disorders, North autism. The concordance rates in monozygotic technologies can detect differences in DNA copy Shore–Long Island Jewish Health System, 4300 Hempstead 9 twins are 70% for autism and 90% for ASD, number at much higher resolution than cyto- Turnpike, Bethpage, NY 11714, USA. Center for Molecular 7 Neuroscience, Vanderbilt University, Nashville, TN 37232– whereas the concordance rates in dizygotic twins genetic methods ( ) and, hence, might reveal 8548, USA. 10Departments of Genetics and Development, are 5% and 10%, respectively. Previous studies spontaneous mutations that were previously and Pediatrics, Columbia University, New York, NY 10027, suggest autism displays a high degree of genetic unidentified. These techniques have shown an USA. 11Behavioural and Brain Sciences Unit, Institute of Child Health, University College London, 30 Guilford Street, heterogeneity. Efforts to map disease genes using abundance of copy number variants (CNVs) in 12 linkage analysis have found evidence for autism humans (8, 9), and the same methods have been London WCIN 1EH, UK. Interdepartmental Program in the Neurosciences, Program in Neurogenetics, Neurology Depart- loci on 20 different chromosomes. Regions used to find de novo chromosome aberrations ment, David Geffen School of Medicine, University of California implicated by multiple studies include 1p, 5q, below the resolution of microscopy in children at Los Angeles, Los Angeles, CA 90095–1769, USA. 13Depart- 7q, 15q, 16p, 17q, 19p, and Xq (2). Moreover, with mental retardation and dysmorphic features ment of Human Genetics, The University of Chicago, 920 East 14 microscopy studies have identified cytogenetic (10–14), including patients with syndromic 58th Street, Chicago, IL 60637, USA. Department of 15 Epidemiology and Population Health, Albert Einstein College abnormalities in >5% of affected children, forms of autism ( ). Yet, the association of ofMedicine,Bronx,NY10461,USA. involving many different loci on all chromo- spontaneous CNVs in idiopathic autism has not *These authors contributed equally to this work. somes (3). In some rare syndromic forms of been systematically investigated. Thus, a large- †To whom correspondence should be addressed. E-mail: autism, such as Rett syndrome (4) and tuberous scale study of genome copy number variation in [email protected] (J.S.); [email protected] (M.W.)

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