Ultrafast Resonant Polarization Interferometry: Towards the First Direct Detection of Vacuum Polarization

Vacuum polarization, an effect predicted nearly 70 years ago, is still yet to be directly detected despite significant experimental effort. Previous attempts have made use of large liquid-helium cooled electromagnets which inadvertently generate spurious signals that mask the desired signal. We present a novel approach for the ultra-sensitive detection of optical birefringence that can be usefully applied to a laboratory detection of vacuum polarization. The new technique has a predicted birefringence measurement sensitivity of $\Delta n \sim 10^{20}$ in a 1 second measurement. When combined with the extreme polarizing fields achievable in this design we predict that a vacuum polarization signal will be seen in a measurement of just a few days in duration.Comment: 9 pages, 2 figures. submitted to PR

Sub-dekahertz ultraviolet spectroscopy of 199Hg+

Using a laser that is frequency-locked to a Fabry-Perot etalon of high finesse and stability, we probe the 5d10 6s 2S_1/2 (F=0) - 5d9 6s 2D_5/2 (F=2) Delta-m_F = 0 electric-quadrupole transition of a single laser-cooled 199Hg+ ion stored in a cryogenic radio-frequency ion trap. We observe Fourier-transform limited linewidths as narrow as 6.7 Hz at 282 nm (1.06 X 10^15 Hz), yielding a line Q = 1.6 X 10^14. We perform a preliminary measurement of the 5d9 6s2 2D_5/2 electric-quadrupole shift due to interaction with the static fields of the trap, and discuss the implications for future trapped-ion optical frequency standards.Comment: 4 pages, 4 figures, submitted for publicatio

Geophysical studies with laser-beam detectors of gravitational waves

The existing high technology laser-beam detectors of gravitational waves may find very useful applications in an unexpected area - geophysics. To make possible the detection of weak gravitational waves in the region of high frequencies of astrophysical interest, ~ 30 - 10^3 Hz, control systems of laser interferometers must permanently monitor, record and compensate much larger external interventions that take place in the region of low frequencies of geophysical interest, ~ 10^{-5} - 3 X 10^{-3} Hz. Such phenomena as tidal perturbations of land and gravity, normal mode oscillations of Earth, oscillations of the inner core of Earth, etc. will inevitably affect the performance of the interferometers and, therefore, the information about them will be stored in the data of control systems. We specifically identify the low-frequency information contained in distances between the interferometer mirrors (deformation of Earth) and angles between the mirrors' suspensions (deviations of local gravity vectors and plumb lines). We show that the access to the angular information may require some modest amendments to the optical scheme of the interferometers, and we suggest the ways of doing that. The detailed evaluation of environmental and instrumental noises indicates that they will not prevent, even if only marginally, the detection of interesting geophysical phenomena. Gravitational-wave instruments seem to be capable of reaching, as a by-product of their continuous operation, very ambitious geophysical goals, such as observation of the Earth's inner core oscillations.Comment: 29 pages including 8 figures, modifications and clarifications in response to referees' comments, to be published in Class. Quant. Gra

Mapping and sequencing of structural variation from eight human genomes

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale - particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone- based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high- resolution sequence map of human structural variation - a standard for genotyping platforms and a prelude to future individual genome sequencing projects

Diversity of human copy number variation and multicopy genes

Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes similar to 1000 genes accessible to genetic studies of disease association

Diversity of human copy number variation and multicopy genes

Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million “singly unique nucleotide” positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association

Characterization of missing human genome sequences and copy-number polymorphic insertions

The extent of human genomic structural variation suggests that there must be portions of the genome yet to be discovered, annotated and characterized at the sequence level. We present a resource and analysis of 2,363 new insertion sequences corresponding to 720 genomic loci. We found that a substantial fraction of these sequences are either missing, fragmented or misassigned when compared to recent de novo sequence assemblies from short-read next-generation sequence data. We determined that 18-37% of these new insertions are copy-number polymorphic, including loci that show extensive population stratification among Europeans, Asians and Africans. Complete sequencing of 156 of these insertions identified new exons and conserved noncoding sequences not yet represented in the reference genome. We developed a method to accurately genotype these new insertions by mapping next-generation sequencing datasets to the breakpoint, thereby providing a means to characterize copy-number status for regions previously inaccessible to single-nucleotide polymorphism microarrays

Scie

Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million “singly unique nucleotide” positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association