Genome-wide linkage using the Social Responsiveness Scale in Utah autism pedigrees

<p>Abstract</p> <p>Background</p> <p>Autism Spectrum Disorder<b>s </b>(ASD) are phenotypically heterogeneous, characterized by impairments in the development of communication and social behaviour and the presence of repetitive behaviour and restricted interests. Dissecting the genetic complexity of ASD may require phenotypic data reflecting more detail than is offered by a categorical clinical diagnosis. Such data are available from the Social Responsiveness Scale (SRS) which is a continuous, quantitative measure of social ability giving scores that range from significant impairment to above average ability.</p> <p>Methods</p> <p>We present genome-wide results for 64 multiplex and extended families ranging from two to nine generations. SRS scores were available from 518 genotyped pedigree subjects, including affected and unaffected relatives. Genotypes from the Illumina 6 k single nucleotide polymorphism panel were provided by the Center for Inherited Disease Research. Quantitative and qualitative analyses were done using MCLINK, a software package that uses Markov chain Monte Carlo (MCMC) methods to perform multilocus linkage analysis on large extended pedigrees.</p> <p>Results</p> <p>When analysed as a qualitative trait, linkage occurred in the same locations as in our previous affected-only genome scan of these families, with findings on chromosomes 7q31.1-q32.3 [heterogeneity logarithm of the odds (HLOD) = 2.91], 15q13.3 (HLOD = 3.64), and 13q12.3 (HLOD = 2.23). Additional positive qualitative results were seen on chromosomes 6 and 10 in regions that may be of interest for other neuropsychiatric disorders. When analysed as a quantitative trait, results replicated a peak found in an independent sample using quantitative SRS scores on chromosome 11p15.1-p15.4 (HLOD = 2.77). Additional positive quantitative results were seen on chromosomes 7, 9, and 19.</p> <p>Conclusions</p> <p>The SRS linkage peaks reported here substantially overlap with peaks found in our previous affected-only genome scan of clinical diagnosis. In addition, we replicated a previous SRS peak in an independent sample. These results suggest the SRS is a robust and useful phenotype measure for genetic linkage studies of ASD. Finally, analyses of SRS scores revealed linkage peaks overlapping with evidence from other studies of neuropsychiatric diseases. The information available from the SRS itself may, therefore, reveal locations for autism susceptibility genes that would not otherwise be detected.</p

The Calibration of Monochromatic Far-Infrared Star Formation Rate Indicators

(Abridged) Spitzer data at 24, 70, and 160 micron and ground-based H-alpha images are analyzed for a sample of 189 nearby star-forming and starburst galaxies to investigate whether reliable star formation rate (SFR) indicators can be defined using the monochromatic infrared dust emission centered at 70 and 160 micron. We compare recently published recipes for SFR measures using combinations of the 24 micron and observed H-alpha luminosities with those using 24 micron luminosity alone. From these comparisons, we derive a reference SFR indicator for use in our analysis. Linear correlations between SFR and the 70 and 160 micron luminosity are found for L(70)>=1.4x10^{42} erg/s and L(160)>=2x10^{42} erg/s, corresponding to SFR>=0.1-0.3 M_sun/yr. Below those two luminosity limits, the relation between SFR and 70 micron (160 micron) luminosity is non-linear and SFR calibrations become problematic. The dispersion of the data around the mean trend increases for increasing wavelength, becoming about 25% (factor ~2) larger at 70 (160) micron than at 24 micron. The increasing dispersion is likely an effect of the increasing contribution to the infrared emission of dust heated by stellar populations not associated with the current star formation. The non-linear relation between SFR and the 70 and 160 micron emission at faint galaxy luminosities suggests that the increasing transparency of the interstellar medium, decreasing effective dust temperature, and decreasing filling factor of star forming regions across the galaxy become important factors for decreasing luminosity. The SFR calibrations are provided for galaxies with oxygen abundance 12+Log(O/H)>8.1. At lower metallicity the infrared luminosity no longer reliably traces the SFR because galaxies are less dusty and more transparent.Comment: 69 pages, 19 figures, 2 tables; accepted for publication on Ap

Dust heating sources in galaxies: the case of M33 (HERM33ES)

Dust emission is one of the main windows to the physics of galaxies and to star formation as the radiation from young, hot stars is absorbed by the dust and reemitted at longer wavelengths. The recently launched Herschel satellite now provides a view of dust emission in the far-infrared at an unequaled resolution and quality up to 500 \mu m. In the context of the Herschel HERM33ES open time key project, we are studying the moderately inclined Scd local group galaxy M33 which is located only 840 kpc away. In this article, using Spitzer and Herschel data ranging from 3.6 \mu m to 500 \mu m, along with HI, H\alpha\ maps, and GALEX ultraviolet data we have studied the emission of the dust at the high spatial resolution of 150 pc. Combining Spitzer and Herschel bands, we have provided new, inclination corrected, resolved estimators of the total infrared brightness and of the star formation rate from any combination of these bands. The study of the colors of the warm and cold dust populations shows that the temperature of the former is, at high brightness, dictated by young massive stars but, at lower brightness, heating is taken over by the evolved populations. Conversely, the temperature of the cold dust is tightly driven by the evolved stellar populations.Comment: 29 pages, 12 figures, accepted for publication in A

The Spitzer Infrared Nearby Galaxies Survey: A High-Resolution Spectroscopy Anthology

High resolution mid-infrared spectra are presented for 155 nuclear and extranuclear regions from the Spitzer Infrared Nearby Galaxies Survey (SINGS). The fluxes for nine atomic forbidden and three molecular hydrogen mid-infrared emission lines are also provided, along with upper limits in key lines for infrared-faint targets. The SINGS sample shows a wide range in the ratio of [SIII]18.71um/[SIII]33.48um, but the average ratio of the ensemble indicates a typical interstellar electron density of 300-400 cm^{-3} on ~23"x15" scales and 500-600 cm^{-3} using ~11"x9" apertures, independent of whether the region probed is a star-forming nuclear, a star-forming extranuclear, or an AGN environment. Evidence is provided that variations in gas-phase metallicity play an important role in driving variations in radiation field hardness, as indicated by [NeIII]15.56um/[NeII]12.81um, for regions powered by star formation. Conversely, the radiation hardness for galaxy nuclei powered by accretion around a massive black hole is independent of metal abundance. Furthermore, for metal-rich environments AGN are distinguishable from star-forming regions by significantly larger [NeIII]15.56um/[NeII]12.81um ratios. Finally, [FeII]25.99um/[NeII]12.81um versus [SiII]34.82um/[SIII]33.48um also provides an empirical method for discerning AGN from normal star-forming sources. However, similar to [NeIII]15.56um/[NeII]12.81um, these mid-infrared line ratios lose their AGN/star-formation diagnostic powers for very low metallicity star-forming systems with hard radiation fields.Comment: Accepted for publication in Ap

ISM Properties in Low-Metallicity Environments II. The Dust Spectral Energy Distribution of NGC 1569

We present new 450 and 850 microns SCUBA data of the dwarf galaxy NGC 1569. We construct the mid-infrared to millimeter SED of NGC 1569, using ISOCAM, ISOPHOT, IRAS, KAO, SCUBA and MAMBO data, and model the SED in order to explore the nature of the dust in low metallicity environments. The detailed modeling is performed in a self-consistent way, synthesizing the global ISRF of the galaxy using an evolutionary synthesis model with further constraints provided by the observed MIR ionic lines and a photoionisation model. Our results show that the dust properties are different in this low metallicity galaxy compared to other more metal rich galaxies. The results indicate a paucity of PAHs probably due to the destructive effects of the ISRF penetrating a clumpy environment and a size-segregation of grains where the emission is dominated by small grains of size ~3 nm, consistent with the idea of shocks having a dramatic effect on the dust properties in NGC 1569. A significant millimetre excess is present in the dust SED which can be explained by the presence of ubiquitous very cold dust (T = 5-7 K). This dust component accounts for 40 to 70 % of the total dust mass in the galaxy (1.6 - 3.4 10^5 Msol) and could be distributed in small clumps (size a few pc) throughout the galaxy. We find a gas-to-dust mass ratio of 740 - 1600, larger than that of the Galaxy and a dust-to-metals ratio of 1/4 to 1/7. We generate an extinction curve for NGC 1569, consistent with the modeled dust size distribution. This extinction curve has relatively steep FUV rise and smaller 2175 Angstroms bump, resembling the observed extinction curve of some regions in the Large Magellanic Cloud.Comment: 20 pages, 20 figures, accepted by A&

Warm Dust and Spatially Variable PAH Emission in the Dwarf Starburst Galaxy NGC 1705

We present Spitzer observations of the dwarf starburst galaxy NGC 1705 obtained as part of SINGS. The galaxy morphology is very different shortward and longward of ~5 microns: short-wavelength imaging shows an underlying red stellar population, with the central super star cluster (SSC) dominating the luminosity; longer-wavelength data reveals warm dust emission arising from two off-nuclear regions offset by ~250 pc from the SSC. These regions show little extinction at optical wavelengths. The galaxy has a relatively low global dust mass (~2E5 solar masses, implying a global dust-to-gas mass ratio ~2--4 times lower than the Milky Way average). The off-nuclear dust emission appears to be powered by photons from the same stellar population responsible for the excitation of the observed H Alpha emission; these photons are unassociated with the SSC (though a contribution from embedded sources to the IR luminosity of the off-nuclear regions cannot be ruled out). Low-resolution IRS spectroscopy shows moderate-strength PAH emission in the 11.3 micron band in the eastern peak; no PAH emission is detected in the SSC or the western dust emission complex. There is significant diffuse 8 micron emission after scaling and subtracting shorter wavelength data; the spatially variable PAH emission strengths revealed by the IRS data suggest caution in the interpretation of diffuse 8 micron emission as arising from PAH carriers alone. The metallicity of NGC 1705 falls at the transition level of 35% solar found by Engelbracht and collaborators; the fact that a system at this metallicity shows spatially variable PAH emission demonstrates the complexity of interpreting diffuse 8 micron emission. A radio continuum non-detection, NGC 1705 deviates significantly from the canonical far-IR vs. radio correlation. (Abridged)Comment: ApJ, in press; please retrieve full-resolution version from http://www.astro.wesleyan.edu/~cannon/pubs.htm

BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions

Thermogenesis in brown adipose tissue (BAT) is fundamental to energy balance and is also relevant for humans. Bone morphogenetic proteins (BMPs) regulate adipogenesis, and, here, we describe a role for BMP8B in the direct regulation of thermogenesis. BMP8B is induced by nutritional and thermogenic factors in mature BAT, increasing the response to noradrenaline through enhanced p38MAPK/CREB signaling and increased lipase activity. Bmp8b(-/-) mice exhibit impaired thermogenesis and reduced metabolic rate, causing weight gain despite hypophagia. BMP8B is also expressed in the hypothalamus, and Bmp8b(-/-) mice display altered neuropeptide levels and reduced phosphorylation of AMP-activated protein kinase (AMPK), indicating an anorexigenic state. Central BMP8B treatment increased sympathetic activation of BAT, dependent on the status of AMPK in key hypothalamic nuclei. Our results indicate that BMP8B is a thermogenic protein that regulates energy balance in partnership with hypothalamic AMPK. BMP8B may offer a mechanism to specifically increase energy dissipation by BAT

The Nature of Infrared Emission in the Local Group Dwarf Galaxy NGC 6822 As Revealed by Spitzer

We present Spitzer imaging of the metal-deficient (Z ~30% Z_sun) Local Group dwarf galaxy NGC 6822. On spatial scales of ~130 pc, we study the nature of IR, H alpha, HI, and radio continuum emission. Nebular emission strength correlates with IR surface brightness; however, roughly half of the IR emission is associated with diffuse regions not luminous at H alpha (as found in previous studies). The global ratio of dust to HI gas in the ISM, while uncertain at the factor of ~2 level, is ~25 times lower than the global values derived for spiral galaxies using similar modeling techniques; localized ratios of dust to HI gas are about a factor of five higher than the global value in NGC 6822. There are strong variations (factors of ~10) in the relative ratios of H alpha and IR flux throughout the central disk; the low dust content of NGC 6822 is likely responsible for the different H alpha/IR ratios compared to those found in more metal-rich environments. The H alpha and IR emission is associated with high-column density (> ~1E21 cm^-2) neutral gas. Increases in IR surface brightness appear to be affected by both increased radiation field strength and increased local gas density. Individual regions and the galaxy as a whole fall within the observed scatter of recent high-resolution studies of the radio-far IR correlation in nearby spiral galaxies; this is likely the result of depleted radio and far-IR emission strengths in the ISM of this dwarf galaxy.Comment: ApJ, in press; please retrieve full-resolution version from http://www.astro.wesleyan.edu/~cannon/pubs.htm

An Ultraviolet-to-Radio Broadband Spectral Atlas of Nearby Galaxies

The ultraviolet-to-radio continuum spectral energy distributions are presented for all 75 galaxies in the Spitzer Infrared Nearby Galaxies Survey (SINGS). A principal component analysis of the sample shows that most of the sample's spectral variations stem from two underlying components, one representative of a galaxy with a low infrared-to-ultraviolet ratio and one representative of a galaxy with a high infrared-to-ultraviolet ratio. The influence of several parameters on the infrared-to-ultraviolet ratio is studied (e.g., optical morphology, disk inclination, far-infrared color, ultraviolet spectral slope, and star formation history). Consistent with our understanding of normal star-forming galaxies, the SINGS sample of galaxies in comparison to more actively star-forming galaxies exhibits a larger dispersion in the infrared-to-ultraviolet versus ultraviolet spectral slope correlation. Early type galaxies, exhibiting low star formation rates and high optical surface brightnesses, have the most discrepant infrared-to-ultraviolet correlation. These results suggest that the star formation history may be the dominant regulator of the broadband spectral variations between galaxies. Finally, a new discovery shows that the 24 micron morphology can be a useful tool for parametrizing the global dust temperature and ultraviolet extinction in nearby galaxies. The dust emission in dwarf/irregular galaxies is clumpy and warm accompanied by low ultraviolet extinction, while in spiral galaxies there is typically a much larger diffuse component of cooler dust and average ultraviolet extinction. For galaxies with nuclear 24 micron emission, the dust temperature and ultraviolet extinction are relatively high compared to disk galaxies.Comment: Accepted for publication in the Astrophysical Journal; Fixed radio flux density units (mJy