Abstract:
:Rare genetic variants have recently been studied for genome-wide associations with human complex diseases. Existing rare variant methods are based on the hypothesis-testing framework that predefined variant sets need to be tested separately. The power of those methods is contingent upon accurate selection of variants for testing, and frequently, common variants are left out for separate testing. In this article, we present a novel Bayesian method for simultaneous testing of all genome-wide variants across the whole frequency range. The method allows for much more flexible grouping of variants and dynamically combines them for joint testing. The method accounts for correlation among variant sets, such that only direct associations with the disease are reported, whereas indirect associations due to linkage disequilibrium are not. Consequently, the method can obtain much improved power and flexibility and simultaneously pinpoint multiple disease variants with high resolution. Additional covariates of categorical, discrete, and continuous values can also be added. We compared our method with seven existing categories of approaches for rare variant mapping. We demonstrate that our method achieves similar power to the best methods available to date when testing very rare variants in small SNP sets. When moderately rare or common variants are included, or when testing a large collection of variants, however, our method significantly outperforms all existing methods evaluated in this study. We further demonstrate the power and the usage of our method in a whole-genome resequencing study of type 1 diabetes.
journal_name
Geneticsjournal_title
Geneticsauthors
Zhang Y,Ghosh S,Hakonarson Hdoi
10.1534/genetics.114.167403subject
Has Abstractpub_date
2014-11-01 00:00:00pages
867-78issue
3eissn
0016-6731issn
1943-2631pii
genetics.114.167403journal_volume
198pub_type
杂志文章相关文献
GENETICS文献大全abstract::RNAs are localized by microtubule-based pathways to both the anterior and posterior poles of the developing Drosophila oocyte. We describe a new gene, wispy, required for localization of mRNAs to both poles of the egg. Embryos from wispy mothers arrest development after abnormal oocyte meiosis and failure of pronuclei...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
abstract::Two variations of the method of localized mutagenesis were used to introduce mutations into the 72 min region of the Escherichia coli chromosome. Twenty temperature-sensitive mutants, with linkage to markers in this region, have been examined. Each strain showed an inhibition of growth in liquid medium at 44 degrees, ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::Mismatch repair of palindromic loops in the presence or absence of single-base mismatches was investigated in wild-type and mismatch-binding defective mutant Chinese hamster ovary cells. Recombination intermediates with a maximum heteroduplex DNA (hDNA) region of 697 bp contained a centrally located, phenotypically si...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::Self-incompatibility (SI) is a genetic system found in some hermaphrodite plants. Recognition of pollen by pistils expressing cognate specificities at two linked genes leads to rejection of self pollen and pollen from close relatives, i.e., to avoidance of self-fertilization and inbred matings, and thus increased outc...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.111.127399
更新日期:2011-07-01 00:00:00
abstract::Genetic screens in Drosophila melanogaster and other organisms have been pursued to filter the genome for genetic functions important for memory formation. Such screens have employed primarily chemical or transposon-mediated mutagenesis and have identified numerous mutants including classical memory mutants, dunce and...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.114.173575
更新日期:2015-04-01 00:00:00
abstract::To assess the reliability of genetic markers it is important to compare inferences that are based on them to a priori expectations. In this article we present an analysis of microsatellite variation within and among populations of island foxes (Urocyon littoralis) on California's Channel Islands. We first show that mi...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::Within the context of a conservation program the management of subdivided populations implies a compromise between the control of the global genetic diversity, the avoidance of high inbreeding levels, and, sometimes, the maintenance of a certain degree of differentiation between subpopulations. We present a dynamic an...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.107.083816
更新日期:2008-05-01 00:00:00
abstract::The polarized partitioning of proteins in cells underlies asymmetric cell division, which is an important driver of development and cellular diversity. The budding yeast Saccharomyces cerevisiae divides asymmetrically, like many other cells, to generate two distinct progeny cells. A well-known example of an asymmetric...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.120.303439
更新日期:2020-11-01 00:00:00
abstract::The DC2 gene was isolated previously on the basis of sequence similarity to DC0, the major Drosophila protein kinase A (PKA) catalytic subunit gene. We show here that the 67-kD Drosophila DC2 protein behaves as a PKA catalytic subunit in vitro. DC2 is transcribed in mesodermal anlagen of early embryos. This expression...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Timely spindle disassembly is essential for coordination of mitotic exit with cytokinesis. In the budding yeast Saccharomyces cerevisiae, the microtubule-associated protein She1 functions in one of at least three parallel pathways that promote spindle disassembly. She1 phosphorylation by the Aurora kinase Ipl1 facilit...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.114.163238
更新日期:2014-11-01 00:00:00
abstract::Animal microRNAs (miRNA) are implicated in the control of nearly all cellular functions. Due to high sequence redundancy within the miRNA gene pool, loss of most of these 21- to 24-bp long RNAs individually does not cause a phenotype. Thus, only very few miRNAs have been associated with clear functional roles. We cons...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.112.145383
更新日期:2012-12-01 00:00:00
abstract::Florida teosinte from Honduras and Guanajuato teosinte have most of their knobs internally located and a common inversion in the short arm of chromosome 8. Teosintes from northern Guatemala, Huixta and Monajil, have all their knobs terminally located and do not have any inversions. Therefore, Florida teosinte from Hon...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::LARK is an essential Drosophila RNA-binding protein of the RNA recognition motif (RRM) class that functions during embryonic development and for the circadian regulation of adult eclosion. LARK protein contains three consensus RNA-binding domains: two RRM domains and a retroviral-type zinc finger (RTZF). To show that ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
abstract::beta-Alanine synthase (EC 3.5.1.6), which catalyzes the final step of pyrimidine catabolism, has only been characterized in mammals. A Saccharomyces kluyveri pyd3 mutant that is unable to grow on N-carbamyl-beta-alanine as the sole nitrogen source and exhibits diminished beta-alanine synthase activity was used to clon...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract::We propose a new method for calculating probabilities for pedigree genetic data that incorporates crossover interference using the chi-square models. Applications include relationship inference, genetic map construction, and linkage analysis. The method is based on importance sampling of unobserved inheritance pattern...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
abstract::If multiple linked polymorphisms are under natural selection, then conflicts arise and the efficiency of natural selection is hindered relative to the case of no linkage. This simple interaction between linkage and natural selection creates an opportunity for mutations that raise the level of recombination to increase...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::The micronutrient boron is essential in maintaining the structure of plant cell walls and is critical for high yields in crop species. Boron can move into plants by diffusion or by active and facilitated transport mechanisms. We recently showed that mutations in the maize boron efflux transporter ROTTEN EAR (RTE) caus...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.116.198275
更新日期:2017-08-01 00:00:00
abstract::The three-dimensional (3D) organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects remain debated. To determine how changes in chromosome positioning affect transcription across thousands of genes with minimal perturbation, we characterized nuclear organization an...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.119.302978
更新日期:2020-03-01 00:00:00
abstract::A method for estimating the average level of gene flow among populations is introduced. The method provides an estimate of Nm, where N is the size of each local population in an island model and m is the migration rate. This method depends on knowing the phylogeny of the nonrecombining segments of DNA that are sampled...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::Movement of transposons causes insertions, deletions, and chromosomal rearrangements potentially leading to premature lethality in Drosophila melanogaster. To repress these elements and combat genomic instability, eukaryotes have evolved several small RNA-mediated defense mechanisms. Specifically, in Drosophila somati...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.115.177196
更新日期:2016-01-01 00:00:00
abstract::It is well known that an allele causing increased recombination is expected to proliferate as a result of genetic drift in a finite population undergoing selection, without requiring other mechanisms. This is supported by recent simulations apparently demonstrating that, in small populations, drift is more important t...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract::In lytic cycle crosses with Red-Gam-lambda phage, particles were examined that had undergone an Int-mediated exchange. It was assumed that this exchange dimerized the circular lambda, making it packageable. Among these Int-mediated recombinants, particles were identified that had, in addition, enjoyed a close double e...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1984-12-01 00:00:00
abstract::Renal agenesis (RA) is one of the more extreme examples of congenital anomalies of the kidney and urinary tract (CAKUT). Bilateral renal agenesis is almost invariably fatal at birth, and unilateral renal agenesis can lead to future health issues including end-stage renal disease. Genetic investigations have identified...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.117.1125
更新日期:2017-09-01 00:00:00
abstract::Studies in the fly, Drosophila melanogaster, have revealed that several signaling pathways are important for the regulation of growth. Among these, the insulin receptor/phosphoinositide 3-kinase (PI3K) pathway is remarkable in that it affects growth and final size without disturbing pattern formation. We have used a s...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.105.045021
更新日期:2005-10-01 00:00:00
abstract::The alpha-Amylase locus in Drosophila pseudoobscura is a multigene family of one, two or three copies on the third chromosome. The nucleotide sequences of the three Amylase genes from a single chromosome of D. pseudoobscura are presented. The three Amylase genes differ at about 0.5% of their nucleotides. Each gene has...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::Population structure parameters commonly used for diploid species are reexamined for the particular case of tetrasomic inheritance (autotetraploid species). Recurrence equations that describe the evolution of identity probabilities for neutral genes in an "island model" of population structure are derived assuming tet...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract::The behavior of chromosomal inversions in Escherichia coli depends upon the region they affect. Regions flanking the replication terminus have been termed nondivisible zones (NDZ) because inversions ending in the region were either deleterious or not feasible. This regional phenomenon is further analyzed here. Thirty ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::In the present study, we investigated intrachromosomal homologous recombination in a murine hybridoma in which the recipient for recombination, the haploid, endogenous chromosomal immunoglobulin mu-gene bearing a mutation in the constant (Cmu) region, was separated from the integrated single copy wild-type donor Cmu r...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1999-06-01 00:00:00
abstract::Telomere position effects on transcription (TPE, or telomeric silencing) are nucleated by association of nonhistone silencing factors with the telomere and propagated in subtelomeric regions through association of silencing factors with the specifically modified histones H3 and H4. However, the function of histone H2A...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Crossovers (COs) between homologous chromosomes are critical for meiotic chromosome segregation and form in the context of the synaptonemal complex (SC), a meiosis-specific structure that assembles between aligned homologs. During Caenorhabditis elegans meiosis, central region components of the SC (SYP proteins) are e...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.119.302625
更新日期:2019-10-01 00:00:00