Fine mapping in 94 inbred mouse strains using a high-density haplotype resource.

Abstract:

:The genetics of phenotypic variation in inbred mice has for nearly a century provided a primary weapon in the medical research arsenal. A catalog of the genetic variation among inbred mouse strains, however, is required to enable powerful positional cloning and association techniques. A recent whole-genome resequencing study of 15 inbred mouse strains captured a significant fraction of the genetic variation among a limited number of strains, yet the common use of hundreds of inbred strains in medical research motivates the need for a high-density variation map of a larger set of strains. Here we report a dense set of genotypes from 94 inbred mouse strains containing 10.77 million genotypes over 121,433 single nucleotide polymorphisms (SNPs), dispersed at 20-kb intervals on average across the genome, with an average concordance of 99.94% with previous SNP sets. Through pairwise comparisons of the strains, we identified an average of 4.70 distinct segments over 73 classical inbred strains in each region of the genome, suggesting limited genetic diversity between the strains. Combining these data with genotypes of 7570 gap-filling SNPs, we further imputed the untyped or missing genotypes of 94 strains over 8.27 million Perlegen SNPs. The imputation accuracy among classical inbred strains is estimated at 99.7% for the genotypes imputed with high confidence. We demonstrated the utility of these data in high-resolution linkage mapping through power simulations and statistical power analysis and provide guidelines for developing such studies. We also provide a resource of in silico association mapping between the complex traits deposited in the Mouse Phenome Database with our genotypes. We expect that these resources will facilitate effective designs of both human and mouse studies for dissecting the genetic basis of complex traits.

journal_name

Genetics

journal_title

Genetics

authors

Kirby A,Kang HM,Wade CM,Cotsapas C,Kostem E,Han B,Furlotte N,Kang EY,Rivas M,Bogue MA,Frazer KA,Johnson FM,Beilharz EJ,Cox DR,Eskin E,Daly MJ

doi

10.1534/genetics.110.115014

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

1081-95

issue

3

eissn

0016-6731

issn

1943-2631

pii

genetics.110.115014

journal_volume

185

pub_type

杂志文章

相关文献

GENETICS文献大全
  • Comparative analysis of position-effect variegation mutations in Drosophila melanogaster delineates the targets of modifiers.

    abstract::In Drosophila melanogaster, heterochromatin-induced silencing or position-effect variegation (PEV) of a reporter gene has provided insights into the properties of heterochromatin. Class I modifiers suppress PEV, and class II modifiers enhance PEV when the modifier gene is present in fewer than two doses. We have exami...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Sass GL,Henikoff S

    更新日期:1998-02-01 00:00:00

  • Coalescent theory for a partially selfing population.

    abstract::A coalescent theory for a sample of DNA sequences from a partially selfing diploid population and an algorithm for simulating such samples are developed in this article. Approximate formulas are given for the expectation and the variance of the number of segregating sites in a sample of k sequences from n individuals....

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Fu YX

    更新日期:1997-08-01 00:00:00

  • Cloning and sequencing the first HLA gene.

    abstract::This Perspectives article recounts the isolation and sequencing of the first human histocompatibility gene (HLA) in 1980-1981. At the time, general knowledge of the molecules of the immune system was already fairly extensive, and gene rearrangements in the immunoglobulin complex (discovered in 1976) had generated much...

    journal_title:Genetics

    pub_type: 杂志文章,评审

    doi:10.1534/genetics.110.113852

    authors: Jordan BR

    更新日期:2010-04-01 00:00:00

  • A genetic analysis of mortality in pigs.

    abstract::An analysis of mortality is undertaken in two breeds of pigs: Danish Landrace and Yorkshire. Zero-inflated and standard versions of hierarchical Poisson, binomial, and negative binomial Bayesian models were fitted using Markov chain Monte Carlo (MCMC). The objectives of the study were to investigate whether there is s...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.109.110759

    authors: Varona L,Sorensen D

    更新日期:2010-01-01 00:00:00

  • Mapping chromosome rearrangement breakpoints to the physical map of Caenorhabditis elegans by fluorescent in situ hybridization.

    abstract::A scheme for rapidly mapping chromosome rearrangements relative to the physical map of Caenorhabditis elegans is described that is based on hybridization patterns of cloned DNA on meiotic nuclei, as visualized by fluorescent in situ hybridization. From the nearly complete physical map, DNA clones, in yeast artificial ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Albertson DG

    更新日期:1993-05-01 00:00:00

  • Replication-dependent sister chromatid recombination in rad1 mutants of Saccharomyces cerevisiae.

    abstract::Homolog recombination and unequal sister chromatid recombination were monitored in rad1-1/rad1-1 diploid yeast cells deficient for excision repair, and in control cells, RAD1/rad1-1, after exposure to UV irradiation. In a rad1-1/rad1-1 diploid, UV irradiation stimulated much more sister chromatid recombination relativ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Kadyk LC,Hartwell LH

    更新日期:1993-03-01 00:00:00

  • Pairwise comparisons of mitochondrial DNA sequences in subdivided populations and implications for early human evolution.

    abstract::We consider the effect on the distribution of pairwise differences between mitochondrial DNA sequences of the incorporation into the underlying population genetics model of two particular effects that seem realistic for human populations. The first is that the population size was roughly constant before growing to its...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Marjoram P,Donnelly P

    更新日期:1994-02-01 00:00:00

  • Evolutionary conservation of the FLOWERING LOCUS C-mediated vernalization response: evidence from the sugar beet (Beta vulgaris).

    abstract::In many plant species, exposure to a prolonged period of cold during the winter promotes flowering in the spring, a process termed vernalization. In Arabidopsis thaliana, the vernalization requirement of winter-annual ecotypes is caused by the MADS-box gene FLOWERING LOCUS C (FLC), which is a repressor of flowering. D...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.106.069336

    authors: Reeves PA,He Y,Schmitz RJ,Amasino RM,Panella LW,Richards CM

    更新日期:2007-05-01 00:00:00

  • De novo methylation of repeated sequences in Coprinus cinereus.

    abstract::We have examined the stability of duplicated DNA sequences in the sexual phase of the life cycle of the basidiomycete fungus, Coprinus cinereus. We observed premeiotic de novo methylation in haploid nuclei containing either a triplication, a tandem duplication, or an ectopic duplication. Methylation changes were not o...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Freedman T,Pukkila PJ

    更新日期:1993-10-01 00:00:00

  • The promotion of gonadal cell divisions by the Caenorhabditis elegans TRPM cation channel GON-2 is antagonized by GEM-4 copine.

    abstract::The initiation of postembryonic cell divisions by the gonadal precursors of C. elegans requires the activity of gon-2. gon-2 encodes a predicted cation channel (GON-2) of the TRPM subfamily of TRP proteins and is likely to mediate the influx of Ca(2+) and/or Mg(2+). We report here that mutations in gem-4 (gon-2 extrag...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Church DL,Lambie EJ

    更新日期:2003-10-01 00:00:00

  • Development of the Proximal-Anterior Skeletal Elements in the Mouse Hindlimb Is Regulated by a Transcriptional and Signaling Network Controlled by Sall4.

    abstract::The vertebrate limb serves as an experimental paradigm to study mechanisms that regulate development of the stereotypical skeletal elements. In this study, we simultaneously inactivated Sall4 using Hoxb6Cre and Plzf in mouse embryos, and found that their combined function regulates development of the proximal-anterior...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.120.303069

    authors: Chen KQ,Tahara N,Anderson A,Kawakami H,Kawakami S,Nishinakamura R,Pandolfi PP,Kawakami Y

    更新日期:2020-05-01 00:00:00

  • Transmission dynamics of heritable silencing induced by double-stranded RNA in Caenorhabditis elegans.

    abstract::Heritable silencing effects are gene suppression phenomena that can persist for generations after induction. In the majority of RNAi experiments conducted in Caenorhabditis elegans, the silencing response results in a hypomorphic phenotype where the effects recede after the F1 generation. F2 and subsequent generations...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.108.089433

    authors: Alcazar RM,Lin R,Fire AZ

    更新日期:2008-11-01 00:00:00

  • Quantitative trait loci mapping and the genetic basis of heterosis in maize and rice.

    abstract::Despite its importance to agriculture, the genetic basis of heterosis is still not well understood. The main competing hypotheses include dominance, overdominance, and epistasis. NC design III is an experimental design that has been used for estimating the average degree of dominance of quantitative trait loci (QTL) a...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.107.082867

    authors: Garcia AA,Wang S,Melchinger AE,Zeng ZB

    更新日期:2008-11-01 00:00:00

  • Linkage relationships of nine enzyme Loci in sunfishes (lepomis; centrarchidae).

    abstract::Linkage relationships of nine enzyme loci; aconitase (Acon ), esterase (Est), glucosephosphate isomerase A and B ( Gpi), glycerate-2-dehydrogenase (G2dh), malic enzyme (Me ), phosphoglycerate kinase (Pgk), phosphoglucomutase (Pgm ) and superoxide dismutase (Sod), were investigated in sunfishes (Lepomis, Centrarchidae)...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Pasdar M,Philipp DP,Whitt GS

    更新日期:1984-07-01 00:00:00

  • Inference of Distribution of Fitness Effects and Proportion of Adaptive Substitutions from Polymorphism Data.

    abstract::The distribution of fitness effects (DFE) encompasses the fraction of deleterious, neutral, and beneficial mutations. It conditions the evolutionary trajectory of populations, as well as the rate of adaptive molecular evolution (α). Inferring DFE and α from patterns of polymorphism, as given through the site frequency...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.117.300323

    authors: Tataru P,Mollion M,Glémin S,Bataillon T

    更新日期:2017-11-01 00:00:00

  • Microgeographic differentiation of chromosomal and enzyme polymorphisms in Drosophila persimilis.

    abstract::We studied microgeographic and temporal genetic differentiation in natural populations of Drosophila persimilis with respect to chromosome inversion and enzyme polymorphisms. Both inversion frequencies and allozyme frequencies varied significantly over short distances. Neither differed significantly between morning an...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Taylor CE,Powell JR

    更新日期:1977-04-01 00:00:00

  • On the identification of the rosy locus DNA in Drosophila melanogaster: intragenic recombination mapping of mutations associated with insertions and deletions.

    abstract::DNA extracts of several rosy-mutation-bearing strains were associated with large insertions and deletions in a defined region of the molecular map believed to include the rosy locus DNA. Large-scale, intragenic mapping experiments were carried out that localized these mutations within the boundaries of the previously ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Clark SH,McCarron M,Love C,Chovnick A

    更新日期:1986-04-01 00:00:00

  • Screens for piwi suppressors in Drosophila identify dosage-dependent regulators of germline stem cell division.

    abstract::The Drosophila piwi gene is the founding member of the only known family of genes whose function in stem cell maintenance is highly conserved in both animal and plant kingdoms. piwi mutants fail to maintain germline stem cells in both male and female gonads. The identification of piwi-interacting genes is essential fo...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Smulders-Srinivasan TK,Lin H

    更新日期:2003-12-01 00:00:00

  • High-throughput computer vision introduces the time axis to a quantitative trait map of a plant growth response.

    abstract::Automated image acquisition, a custom analysis algorithm, and a distributed computing resource were used to add time as a third dimension to a quantitative trait locus (QTL) map for plant root gravitropism, a model growth response to an environmental cue. Digital images of Arabidopsis thaliana seedling roots from two ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.113.153346

    authors: Moore CR,Johnson LS,Kwak IY,Livny M,Broman KW,Spalding EP

    更新日期:2013-11-01 00:00:00

  • Statistical tests of neutrality of mutations.

    abstract::Mutations in the genealogy of the sequences in a random sample from a population can be classified as external and internal. External mutations are mutations that occurred in the external branches and internal mutations are mutations that occurred in the internal branches of the genealogy. Under the assumption of sele...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Fu YX,Li WH

    更新日期:1993-03-01 00:00:00

  • Point mutation rate of bacteriophage PhiX174.

    abstract::The point mutation rate of phage PhiX174 was determined using the fluctuation test. After identifying the genetic changes associated with the selected phenotype, we obtained an estimate of 1.0x10(-6) substitutions per base per round of copying, which is consistent with Drake's rule (0.003 mutations per genome per roun...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.109.106005

    authors: Cuevas JM,Duffy S,Sanjuán R

    更新日期:2009-10-01 00:00:00

  • SVF1 regulates cell survival by affecting sphingolipid metabolism in Saccharomyces cerevisiae.

    abstract::Sphingolipid signaling plays an important role in the regulation of central cellular processes, including cell growth, survival, and differentiation. Many of the essential pathways responsible for sphingolipid biogenesis, and key cellular responses to changes in sphingolipid balance, are conserved between mammalian an...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.106.064527

    authors: Brace JL,Lester RL,Dickson RC,Rudin CM

    更新日期:2007-01-01 00:00:00

  • A Critical Role for Dna2 at Unwound Telomeres.

    abstract::Dna2 is a nuclease and helicase that functions redundantly with other proteins in Okazaki fragment processing, double-strand break resection, and checkpoint kinase activation. Dna2 is an essential enzyme, required for yeast and mammalian cell viability. Here, we report that numerous mutations affecting the DNA damage ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.118.300809

    authors: Markiewicz-Potoczny M,Lisby M,Lydall D

    更新日期:2018-05-01 00:00:00

  • Isogenic Strains of PHYCOMYCES BLAKESLEEANUS Suitable for Genetic Analysis.

    abstract::The progeny of crosses between wild-type strains of Phycomyces usually do not exhibit all of the expected genotypes from meiosis. By backcrossing, we have isolated a new (+) mating-type strain, A56, which is nearly isogenic with the (-) wild-type NRRL1555 commonly used in Phycomyces research. Tetrad analysis of the ba...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Alvarez MI,Eslava AP

    更新日期:1983-12-01 00:00:00

  • The nsdC gene encoding a putative C2H2-type transcription factor is a key activator of sexual development in Aspergillus nidulans.

    abstract::The formation of the Aspergillus nidulans fruiting body is affected by a number of genetic and environmental factors. Here, the nsdC (never in sexual development) gene-encoding a putative transcription factor carrying a novel type of zinc-finger DNA-binding domain consisting of two C(2)H(2)'s and a C(2)HC motif that a...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.109.101667

    authors: Kim HR,Chae KS,Han KH,Han DM

    更新日期:2009-07-01 00:00:00

  • Mettl3 Mutation Disrupts Gamete Maturation and Reduces Fertility in Zebrafish.

    abstract::N6-methyladenosine (m6A), catalyzed by Mettl3 methyltransferase, is a highly conserved epigenetic modification in eukaryotic messenger RNA (mRNA). Previous studies have implicated m6A modification in multiple biological processes, but the in vivo function of m6A has been difficult to study, because mettl3 mutants are ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.117.300574

    authors: Xia H,Zhong C,Wu X,Chen J,Tao B,Xia X,Shi M,Zhu Z,Trudeau VL,Hu W

    更新日期:2018-02-01 00:00:00

  • Evolutionary Rescue over a Fitness Landscape.

    abstract::Evolutionary rescue describes a situation where adaptive evolution prevents the extinction of a population facing a stressing environment. Models of evolutionary rescue could in principle be used to predict the level of stress beyond which extinction becomes likely for species of conservation concern, or, conversely, ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.118.300908

    authors: Anciaux Y,Chevin LM,Ronce O,Martin G

    更新日期:2018-05-01 00:00:00

  • Among-environment heteroscedasticity and genetic autocorrelation: implications for the study of phenotypic plasticity.

    abstract::The impact of among-environment heteroscedasticity and genetic autocorrelation on the analysis of phenotypic plasticity is examined. Among-environment heteroscedasticity occurs when genotypic variances differ among environments. Genetic autocorrelation arises whenever the responses of a genotype to different environme...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Dutilleul P,Potvin C

    更新日期:1995-04-01 00:00:00

  • Selection on Glycine beta-1,3-endoglucanase genes differentially inhibited by a Phytophthora glucanase inhibitor protein.

    abstract::Plant endo-beta-1,3-glucanases (EGases) degrade the cell wall polysaccharides of attacking pathogens and release elicitors of additional plant defenses. Isozymes EGaseA and EGaseB of soybean differ in susceptibility to a glucanase inhibitor protein (GIP1) produced by Phytophthora sojae, a major soybean pathogen. EGase...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.103.025098

    authors: Bishop JG,Ripoll DR,Bashir S,Damasceno CM,Seeds JD,Rose JK

    更新日期:2005-02-01 00:00:00

  • The P-3 and EST loci in the honeybee Apis mellifera.

    abstract::Data for Apis mellifera indicate that the P-3 proteins and one esterase enzyme are controlled by two genes, P-3 and Est, with two alleles each. The frequency of the P-3 alleles is different in the two subspecies (adansonii and ligustica), that for P-3(F) in Italian bees being 46.9% and in African 0.5%. The frequency o...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Mestriner MA,Contel EP

    更新日期:1972-12-01 00:00:00