Abstract:
:The genetic etiology of many complex diseases is highly heterogeneous. A complex disease can be caused by multiple mutations within the same gene or mutations in multiple genes at various genomic loci. Although these disease-susceptibility mutations can be collectively common in the population, they are often individually rare or even private to certain families. Family-based studies are powerful for detecting rare variants enriched in families, which is an important feature for sequencing studies due to the heterogeneous nature of rare variants. In addition, family designs can provide robust protection against population stratification. Nevertheless, statistical methods for analyzing family-based sequencing data are underdeveloped, especially those accounting for heterogeneous etiology of complex diseases. In this article, we introduce a random field framework for detecting gene-phenotype associations in family-based sequencing studies, referred to as family-based genetic random field (FGRF). Similar to existing family-based association tests, FGRF could utilize within-family and between-family information separately or jointly to test an association. We demonstrate that FGRF has comparable statistical power with existing methods when there is no genetic heterogeneity, but can improve statistical power when there is genetic heterogeneity across families. The proposed method also shares the same advantages with the conventional family-based association tests (e.g., being robust to population stratification). Finally, we applied the proposed method to a sequencing data from the Minnesota Twin Family Study, and revealed several genes, including SAMD14, potentially associated with alcohol dependence.
journal_name
Geneticsjournal_title
Geneticsauthors
Li M,He Z,Tong X,Witte JS,Lu Qdoi
10.1534/genetics.118.301266subject
Has Abstractpub_date
2018-10-01 00:00:00pages
463-476issue
2eissn
0016-6731issn
1943-2631pii
genetics.118.301266journal_volume
210pub_type
杂志文章相关文献
GENETICS文献大全abstract::Plants regenerated from tissue culture often display somaclonal variation, that is, somatic and often meiotically heritable phenotypic variation that can result from both genetic and epigenetic modifications. To better understand the molecular basis of somaclonal variation, we have characterized four unique tissue cul...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.110.117929
更新日期:2010-11-01 00:00:00
abstract::Two-dimensional paper chromatography was performed on methanol extracts of leaves of hexaploid bread wheat, Triticum aestivum L. em. Thell. cultivar Chinese Spring, and of the available nullisomic-tetrasomic compensating lines, the tetrasomic lines and the ditelocentric lines. The chromatograms had 27 spots identified...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract::Fluorescent in situ hybridization was used to examine the distribution of six abundant long terminal repeat (LTR) retroelements, Opie, Huck, Cinful-1, Prem-2/Ji, Grande, and Tekay/Prem-1 on maize pachytene chromosomes. Retroelement staining in euchromatin was remarkably uniform, even when we included the structurally ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::Birds are characterized by female heterogamety; females carry the Z and W sex chromosomes, while males have two copies of the Z chromosome. We suggest here that full differentiation of the Z and W sex chromosomes of birds did not take place until after the split of major contemporary lineages, in the late Cretaceous. ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2001-05-01 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::We present the results of a restriction site survey of variation at five loci in Drosophila athabasca, complimenting a previous study of the period locus. There is considerably greater differentiation between the three semispecies of D. athabasca at the period locus and two other X-linked genes (no-on-transient-A and ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1996-10-01 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::Natural selection favors alleles that increase the number of offspring produced by their carriers. But in a world that is inherently uncertain within generations, selection also favors alleles that reduce the variance in the number of offspring produced. If previous studies have established this principle, they have l...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.113.156067
更新日期:2014-01-01 00:00:00
abstract::The island model with stochastically variable migration rate and immigrant gene frequency is investigated. It is supposed that the migration rate and the immigrant gene frequency are independent of each other in each generation, and each of them is independently and identically distributed in every generation. The tre...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::Many arthropod species are infected with maternally inherited endosymbionts that induce a shift in the sex ratio of their hosts by feminizing or killing males (cytoplasmic sex-ratio distorters, or SRDs). These endosymbionts can have profound impacts on evolutionary processes of their hosts. Here, I derive analytical e...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.110.120014
更新日期:2010-09-01 00:00:00
abstract::Remarkably complex patterns of aneuploidy have been observed in the genomes of many eukaryotic cell types, ranging from brewing yeasts to tumor cells. Such aberrant karyotypes are generally thought to take shape progressively over many generations, but evidence also suggests that genomes may undergo faster modes of ev...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.120.303536
更新日期:2020-09-01 00:00:00
abstract::Heterochromatin is a specialized chromatin structure in chromosomal regions associated with repeated DNA sequences and low concentrations of genes. Formation of heterochromatin is determined in large part by enzymes that modify histones and structural proteins that bind to these modified histones in a cooperative fash...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.104.030676
更新日期:2004-11-01 00:00:00
abstract::This article focuses on conducting global testing for association between a binary trait and a set of rare variants (RVs), although its application can be much broader to other types of traits, common variants (CVs), and gene set or pathway analysis. We show that many of the existing tests have deteriorating performan...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.114.165035
更新日期:2014-08-01 00:00:00
abstract::We show how the idea of monotone coupling from the past can produce simple algorithms for simulating samples at a nonneutral locus under a range of demographic models. We specifically consider a biallelic locus and either a general variable population size mode or a general migration model for population subdivision. ...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.106.060681
更新日期:2006-11-01 00:00:00
abstract::A two-locus model is used to analyze the effectiveness of a mixture of insecticides in delaying resistance, compared to the use of the insecticides singly. The effects of factors such as recombination, effective dominance, initial value of allele frequencies and initial value of linkage disequilibrium are considered. ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1985-04-01 00:00:00
abstract::The mutational origin and subsequent evolution of de novo genes, which are hypothesized to be genes of recent origin that are not obviously related to ancestral coding sequence, are poorly understood. However, accumulating evidence suggests that such genes may often function in male reproduction. Here we use testis-de...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.106.069245
更新日期:2007-06-01 00:00:00
abstract::We analyzed the dynamics of transposable elements (TEs) according to Wright's island and continent-island models, assuming that selection tends to counter the deleterious effects of TEs. We showed that migration between host populations has no impact on either the existence or the stability of the TE copy number equil...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.104.032243
更新日期:2005-01-01 00:00:00
abstract::The MITF protein is a member of the MYC family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors and is most closely related to the TFE3, TFEC, and TFEB proteins. In the mouse, MITF is required for the development of several different cell types, including the retinal pigment epithelial (RPE) c...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.167.1.233
更新日期:2004-05-01 00:00:00
abstract::Preliminary studies with restriction fragment length polymorphisms of mitochondrial DNA (mtDNA) in natural populations of Drosophila melanogaster revealed considerable variation in terms of nucleotide sequence and overall size. In this report we present data from more isofemale lines and more restriction enzymes, and ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::bld2-1 mutant Chlamydomonas reinhardtii strains assemble basal bodies with singlet microtubules; bld2-1 cells display flagellar assembly defects as well as positioning defects of the mitotic spindle and cleavage furrow. To further understand the role of the BLD2 gene, we have isolated three new bld2 alleles and three ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Variable numbers of tandem repeats (VNTRs) are a class of highly informative and widely dispersed genetic markers. Despite their wide application in biological science, little is known about their mutational mechanisms or population dynamics. The objective of this work was to investigate four summary measures of VNTR ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Transcription is repressed in regions of the fission yeast genome close to centromeres, telomeres, or the silent mating-type cassettes mat2-P and mat3-M. The repression involves the chromo-domain proteins Swi6 and Clr4. We report that two other chromo-domain proteins, Chp1 and Chp2, are also important for these positi...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::Drosophila dishevelled (dsh) functions in two pathways: it is necessary to transduce Wingless (Wg) signaling and it is required in planar cell polarity. To learn more about how Dsh can discriminate between these functions, we performed genetic screens to isolate additional dsh alleles and we examined the potential rol...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::Our previous work suggests that the Nhp6 HMGB protein stimulates RNA polymerase II transcription via the TATA-binding protein TBP and that Nhp6 functions in the same functional pathway as the Gcn5 histone acetyltransferase. In this report we examine the genetic relationship between Nhp6 and Gcn5 with the Mot1 and Ccr4...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.105.050245
更新日期:2006-02-01 00:00:00
abstract::Hybridization between related species results in the formation of an allopolyploid with multiple subgenomes. These subgenomes will each contain complete, yet evolutionarily divergent, sets of genes. Like a diploid hybrid, allopolyploids will have two versions, or homeoalleles, for every gene. Partial functional redund...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.118.301851
更新日期:2019-03-01 00:00:00
abstract::The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for associat...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.111.131813
更新日期:2011-11-01 00:00:00
abstract::Sexual reproduction and recombination are important for maintaining a stable copy number of transposable elements (TEs). In sexual populations, elements can be contained by purifying selection against host carriers with higher element copy numbers; however, in the absence of sex and recombination, asexual populations ...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.106.060434
更新日期:2006-10-01 00:00:00
abstract::F1 hybrids between mouse inbred strains PWD and C57BL/6 represent the most thoroughly genetically defined model of hybrid sterility in vertebrates. Hybrid male sterility can be fully reconstituted from three components of this model, the Prdm9 gene, intersubspecific homeology of Mus musculus musculus and Mus musculus ...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.119.302554
更新日期:2019-11-01 00:00:00
abstract::Interactions between Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs and CRISPR-associated (Cas) proteins form an RNA-guided adaptive immune system in prokaryotes. The adaptive immune system utilizes segments of the genetic material of invasive foreign elements in the CRISPR locus. The loci are ...
journal_title:Genetics
pub_type: 杂志文章
doi:10.1534/genetics.117.202580
更新日期:2017-08-01 00:00:00
abstract::Results of immunogenetic, immunochemical and physicochemical investigations on two serum allotypes of swine are reported. The allotypes, designated Lpr1 and Lpr2, have been identified by specific alloprecipitins in agar gel. Genetic studies indicate that the allotypes are specified by two codominant autosomal allelic ...
journal_title:Genetics
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00