Golgi-localized MORN1 promotes lipid droplet abundance and enhances tolerance to multiple stresses in Arabidopsis

Lipid droplet (LD) in vegetative tissues has recently been implicated in environmental responses in plants, but its regulation and its function in stress tolerance are not well understood. Here, we identified a Membrane Occupation and Recognition Nexus 1 (MORN1) gene as a contributor to natural variations of stress tolerance through genome-wide association study in Arabidopsis thaliana. Characterization of its loss-of-function mutant and natural variants revealed that the MORN1 gene is a positive regulator of plant growth, disease resistance, cold tolerance, and heat tolerance. The MORN1 protein is associated with the Golgi and is also partly associated with LD. Protein truncations that disrupt these associations abolished the biological function of the MORN1 protein. Furthermore, the MORN1 gene is a positive regulator of LD abundance, and its role in LD number regulation and stress tolerance is highly linked. Therefore, this study identifies MORN1 as a positive regulator of LD abundance and a contributor to natural variations of stress tolerance. It implicates a potential involvement of Golgi in LD biogenesis and strongly suggests a contribution of LD to diverse processes of plant growth and stress responses.     

Effect of Photoperiod on the Regulation of Wheat Vernalization Genes VRN1 and VRN2

Wheat is usually classified as a long day (LD) plant because most varieties flower earlier when exposed to longer days. In addition to LD, winter wheats require a long exposure to low temperatures (vernalization) to become competent for flowering. Here we show that in some genotypes this vernalization requirement can be replaced by interrupting the LD treatment by 6 weeks of short day (SD), and that this replacement is associated with the SD down-regulation of the VRN2 flowering repressor. In addition, we found that SD down-regulation of VRN2 at room temperature is not followed by the up-regulation of the meristem identity gene VRN1 until plants are transferred to LD. This result contrasts with the VRN1 up-regulation observed after the VRN2 down-regulation by vernalization, suggesting the existence of a second VRN1 repressor. Analysis of natural VRN1 mutants indicated that a CArG-box located in the VRN1 promoter is the most likely regulatory site for the interaction with this second repressor. Up-regulation of VRN1 under SD in accessions carrying mutations in the CArG-box resulted in an earlier initiation of spike development, compared to other genotypes. However, even the genotypes with CArG box mutations required LD for a normal and timely spike development. The SD acceleration of flowering was observed in photoperiod sensitive winter varieties. Since vernalization requirement and photoperiod sensitivity are ancestral traits in Triticeae species we suggest that wheat was initially a SD–LD plant and that strong selection pressures during domestication and breeding resulted in the modification of this dual regulation. The down-regulation of the VRN2 repressor by SD is likely part of the mechanism associated with the SD–LD regulation of flowering in photoperiod sensitive winter wheat. These authors contributed equally to this work     

The size and phospholipid composition of lipid droplets can influence their proteome

The proteomic makeup of lipid droplets (LDs) is believed to regulate the function of LDs, which are now recognized as important cellular organelles that are associated with many human metabolic disorders. However, factors that help determine LD proteome remain to be identified and characterized. Here we analyzed the phospholipid and protein composition of LDs isolated from wild type (WT) yeast cells, and also from fld1Δ, cds1, and ino2Δ mutant cells which produce ‘supersized’ LDs. LDs of fld1Δ and WT cells exhibited similar phospholipid profiles, whereas LDs of cds1 and ino2Δ strains had a higher (cds1) or lower (ino2Δ) percentage of phosphatidylcholine than those of WT, respectively. Unexpectedly, the presence of most known LD resident proteins was greatly reduced in the LD fraction isolated from cds1 and ino2Δ, including neutral lipid hydrolases. Consistent with this result, mobilization of neutral lipids was seriously impaired in these two strains. Contrary to the reduction of LD resident proteins, the Hsp90 family molecular chaperones, Hsc82 and Hsp82, were greatly increased in the LD fractions of cds1 and ino2Δ strains without changes at the level of expression. These data demonstrate the impact of LD phopholipids and size on the makeup of LD proteome.     

Genome‐wide linkage disequilibrium and past effective population size in three Korean cattle breeds

The routine collection and use of genomic data are useful for effectively managing breeding programs for endangered populations. Linkage disequilibrium (LD) using high‐density DNA markers has been widely used to determine population structures and predict the genomic regions that are associated with economic traits in beef cattle. The extent of LD also provides information about historical events, including past effective population size (N_e), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and N_e in three Korean cattle breeds that are genetically similar but have different coat colors (Brown, Brindle and Jeju Black Hanwoo). Brindle and Jeju Black are endangered breeds with small populations, whereas Brown Hanwoo is the main breeding population in Korea. DNA samples from these cattle breeds were genotyped using the Illumina BovineSNP50 Bead Chip. We examined 13 cattle breeds, including European taurines, African taurines and indicines, and hybrids to compare their LD values. Brown Hanwoo consistently had the lowest mean LD compared to Jeju Black, Brindle and the other 13 cattle breeds (0.13, 0.19, 0.21 and 0.15–0.22 respectively). The high LD values of Brindle and Jeju Black contributed to small N_e values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and N_e for each breed reflect the breeding strategy applied. The N_e for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract.     

An association analysis for 14 candidate genes mapping to meat quality quantitative trait loci in a Duroc pig population reveals that the ATP1A2 genotype is highly associated with muscle electric conductivity

In previous GWAS carried out in a Duroc commercial line (Lipgen population), we detected on pig chromosomes 3, 4 and 14 several QTL for gluteus medius muscle redness (GM a*), electric conductivity in the longissimus dorsi muscle (LD CE) and vaccenic acid content in the LD muscle (LD C18:1 n − 7), respectively. We have genotyped, in the Lipgen population, 19 SNPs mapping to 14 genes located within these QTL. Subsequently, association analyses have been performed. After correction for multiple testing, two SNPs in the TGFBRAP1 (rs321173745) and SELENOI (rs330820437) genes were associated with GM a*, whereas ACADSB (rs81449951) and GPR26 (rs343087568) genotypes displayed significant associations with LD vaccenic content. Moreover, the polymorphisms located at the ATP1A2 (rs344748241), ATP8B2 (rs81382410) and CREB3L4 (rs321278469 and rs330133789) genes showed significant associations with LD CE. We made a second round of association analyses including the SNPs mentioned above as well as other SNPs located in the chromosomes to which they map. After performing a correction for multiple testing, the only association that remained significant at the chromosome-wide level was that between the ATP1A2 genotype and LD CE. From a functional point of view, this association is meaningful because this locus encodes a subunit of the Na⁺/K⁺-ATPase responsible for maintaining an electrochemical gradient across the plasma membrane.     

Spatial Dynamics of Lyme Disease: A Review

Lyme disease (LD), the most frequently reported vector-borne disease in the United States, requires that humans, infected vector ticks, and infected hosts all occur in close spatial proximity. Understanding the spatial dynamics of LD requires an understanding of the spatial determinants of each of these organisms. We review the literature on spatial patterns and environmental correlates of human cases of LD and the vector ticks, Ixodes scapularis in the northeastern and midwestern United States and Ixodes pacificus in the western United States. The results of this review highlight a need for a more standardized and comprehensive approach to studying the spatial dynamics of the LD system. Specifically, we found that the only environmental variable consistently associated with increased LD risk and incidence was the presence of forests. However, the reasons why some forests are associated with higher risk and incidence than others are still poorly understood. We suspect that the discordance among studies is due, in part, to the rapid developments in both conceptual and technological aspects of spatial ecology hastening the obsolescence of earlier approaches. Significant progress in identifying the determinants of spatial variation in LD risk and incidence requires that: (1) existing knowledge of the biology of the individual components of each LD system is utilized in the development of spatial models; (2) spatial data are collected over longer periods of time; (3) data collection and analysis among regions are more standardized; and (4) the effect of the same environmental variables is tested at multiple spatial scales.     

Photoperiod acclimation and 24-hour variations in the critical thermal maxima of a tropical and a temperate frog

Summary The effect of photoperiod on the upper thermal tolerance of two species of frogs was studied by using the critical thermal maximum (CTM) as the end point. Both species are heliotropic and from temperate climates, but Hyla labialis lives under a near constant tropical photoperiod while Rana pipiens lives under a varying temperatezone photoperiod. The CTM of both species was studied over a 24-hour period to determine if a rhythm of temperature tolerance exists. In all but one of the acclimatization conditions used, the CTM of R. pipiens was higher than that of H. labialis. This agrees with what is known of their thermal ecology. Photoperiod significantly affects the CTM of both species. For Rana pipiens long (LD 16:8) photoperiods result in significantly higher thermal tolerance than short (LD 8:16) or moderate (LD 12:12) photoperiods at both 15 and 25° C. H. labialis shows a different pattern, having highest CTM at 25°C, LD 12:12 and lowest at 15°C, LD 12:12. When acclimated to a short (LD 8:16) photoperiod certain aspects of the frogs' tolerance of high temperatures are altered. At the same acclimatization the CTM of R. pipiens is higher than that of H. labialis, except under a combination short light regime and low temperature, and H. labialis at LD 8:16 shows no thermal acclimation between 15 and 25°C. Significant variation in the CTM over a 24-hour period occurred in H. labialis acclimatized at 25°C, LD 12:12 and R. pipiens at 25°C, LD 8:16 and 15°C, LD 12:12. For both species the 24-hour rhythm of temperature tolerance, when it occurs at LD 12:12, might be of adaptive value. Times of highest thermal tolerance are in the late morning or early afternoon and lowest tolerance is during the dark period. For R. pipiens under the unnatural combination of 25°C, LD 8:16, the pattern is reversed. When all three significant cycles are phase shifted so that the times of highest tolerance coincide, the pattern of the curves is very similar.     

Mitochondrial ORF79 levels determine pollen abortion in cytoplasmic male sterile rice

Cytoplasmic male sterility (CMS) is an important agricultural trait characterized by lack of functional pollen, and caused by ectopic and defective mitochondrial gene expression. The pollen function in CMS plants is restored by the presence of nuclear‐encoded restorer of fertility (Rf) genes. Previously, we cloned Rf2, which restores the fertility of Lead Rice (LD)‐type CMS rice. However, neither the function of Rf2 nor the identity of the mitochondrial gene causing CMS has been determined in LD–CMS rice. Here, we show that the mitochondrial gene orf79 acts as a CMS‐associated gene in LD–CMS rice, similar to its role in BT–CMS rice originating from Chinsurah Boro II, and Rf2 weakly restores fertility in BT–CMS rice. We also show that RF2 promotes degradation of atp6–orf79 RNA in a different manner from that of RF1, which is the Rf gene product in BT–CMS rice. The amount of ORF79 protein in LD–CMS rice was one‐twentieth of the amount in BT–CMS rice. The difference in ORF79 protein levels probably accounts for the mild and severe pollen defects in LD–CMS and BT–CMS rice, respectively. In the presence of Rf2, accumulation of ORF79 was reduced to almost zero and 25% in LD–CMS and BT–CMS rice, respectively, which probably accounts for the complete and weak fertility restoration abilities of Rf2 in LD–CMS and BT–CMS rice, respectively. These observations indicate that the amount of ORF79 influences the pollen fertility in two strains of rice in which CMS is induced by orf79.     

Genetic analysis of a streptomycin-resistant Escherichia coli mutant temperature-sensitive for nonsense suppression

Summary Continuing the genetic and biochemical characterization of the streptomycin-resistant Escherichia coli mutant LD1, we confirmed that LD1 is temperature-sensitive for suppression of nonsense codons, and that this phenotype of the mutant and its streptomycin-resistance are genetically linked and are probably caused by a single mutation, strA (LD1). We also isolated a spontaneous revertant, called LD1-R, which partially relieves the restriction of nonsense suppression caused by the strA (LD1) mutation. LD1-R is derived by an additional mutation (revA) which is closely linked to strA (LD1). We further demonstrate that the weak suppression of a lacZ_UGA mutation in a suppressor-free strain, which probably takes place by normal tRNA^Trp, can be detected by the use of the chromagenic substance x-gal (5-Bromo-4-chloro-3-indolyl--d-Galactopyranoside).     

N content of phloem and xylem exudates during the transition to flowering in Sinapis alba and Arabidopsis thaliana

The involvement of nitrogenous substances in the transition to flowering was investigated in Sinapis alba and Arabidopsis thaliana (Columbia). Both species grown in short days (SD) are induced to flower by one long day (LD). In S. alba, the phloem sap (leaf and apical exudates) and the xylem sap (root exudate) were analysed in LD versus SD. In A. thaliana, only the leaf exudate could be analysed but an alternative system for inducing flowering without day‐length extension was used: the displaced SD (DSD). Significant results are: (i) in both species, the leaf exudate was enriched in Gln during the inductive LD, at a time compatible with export of the floral stimulus; (ii) in S. alba, the root export of amino acids decreased in LD, whereas the nitrate remained unchanged – thus the extra‐Gln found in the leaf exudate should originate from the leaves; (iii) extra‐Gln was also found very early in the apical exudate of S. alba in LD, together with more Glu; (iv) in A. thaliana induced by one DSD, the leaf export of Asn increased sharply, instead of Gln in LD. This agrees with Asn prevalence in C‐limited plants. The putative role of amino acids in the transition to flowering is discussed.     

Influence of Photoperiod in Accelerating the Reentrainment in Drosophila

Efficacy of the short photoperiod (Spp) and the long photoperiod (Lpp) in accelerating the reentrainment was assessed in Drosophila biarmipes. The Spp accelerated the reentrainment after the phase advance of light-dark (LD) cycles, which was associated with the early activity onset (Ψo) and the short period of free-running rhythm (τ). The Lpp accelerated the reentrainment after the phase delay of LD cycles, which was associated with the late Ψo and the long τ. This study indicates that the photoperiodic modulation of the circadian waveform of the underlying pacemaker that controls activity rhythm influenced the rate of reentrainment in D. biarmipes. (Author correspondence: drdsjoshi08@gmail.com)     

Enhanced growth and total fatty acid production of microalgae under various lighting conditions induced by flashing light

Microalgae are gaining importance as a source of high‐value bioproducts. However, data regarding optimization of algal productivity via variation of environmental factors are lacking. Here, we evaluated a novel lighting method for the enhancement of biomass and total fatty acid (TFA) productivities during algal cultivation. We cultivated six different algal strains (Chlorella vulgaris KCTC AG10002, Acutodesmus obliquus KGE18, Uronema sp. KGE03, Micractinium reisseri KGE19, Fragilaria sp., and Spirogyra sp.) under various lighting conditions—continuous light (CL), light‐dark cycle (LD), and continuous dark (CD)—with or without additional flashing light. We monitored dry cell weight (DCW) and TFA concentrations during cultivation. For each algal strain, the growth rate showed markedly different responses to the various lighting modes. The growth rates of C. vulgaris KCTC AG10002 (1.34‐fold DCW increase, LD with flash), A. obliquus KGE18 (5.16‐fold DCW increase, LD with flash), Uronema sp. KGE03 (2.77‐fold DCW increase, CL with flash), and M. reisseri KGE19 (1.52‐fold DCW increase, CL with flash) markedly increased in response to flashing light. Additionally, in some algal strains cultivated under the LD mode, the flashing light treatment induced increased TFA concentrations (C. vulgaris, 1.19‐fold increase; A. obliquus, 2.59‐fold increase; and M. reisseri, 3.31‐fold increase). Phytohormone analysis of M. reisseri revealed increases in growth rate and TFA concentrations, associated with phytohormone induction via flashing light (e.g. 2.93‐fold increase in gibberellic acid); hence, flashing light can promote substantial alterations in algal metabolism.     

Migratory flexibility in native Hawai'ian amphidromous fishes

We assessed the prevalence of life history variation across four of the five native amphidromous Hawai'ian gobioids to determine whether some or all exhibit evidence of partial migration. Analysis of otolith Sr.: Ca concentrations affirmed that all are amphidromous and revealed evidence of partial migration in three of the four species. We found that 25% of Lentipes concolor (n = 8), 40% of Eleotris sandwicensis (n = 20) and 29% of Stenogobius hawaiiensis (n = 24) did not exhibit a migratory life-history. In contrast, all individuals of Sicyopterus stimpsoni (n = 55) included in the study went to sea as larvae. Lentipes concolor exhibited the shortest mean larval duration (LD) at 87 days, successively followed by E. sandwicensis (mean LD = 102 days), S. hawaiiensis (mean LD = 114 days) and S. stimpsoni (mean LD = 120 days). These findings offer a fresh perspective on migratory life histories that can help improve efforts to conserve and protect all of these and other at-risk amphidromous species that are subject to escalating anthropogenic pressures in both freshwater and marine environments.     

Impulsiveness mediates the association between GABRA2 SNPs and lifetime alcohol problems

Genetic variants in GABRA2 have previously been shown to be associated with alcohol measures, electroencephalography (EEG) β waves and impulsiveness‐related traits. Impulsiveness is a behavioral risk factor for alcohol and other substance abuse. Here, we tested association between 11 variants in GABRA2 with NEO‐impulsiveness and problem drinking. Our sample of 295 unrelated adult subjects was from a community of families with at least one male with DSM‐IV alcohol use diagnosis, and from a socioeconomically comparable control group. Ten GABRA2 SNPs (single‐nucleotide polymorphisms) were associated with the NEO‐impulsiveness (P < 0.03). The alleles associated with higher impulsiveness correspond to the minor alleles identified in previous alcohol dependence studies. All ten SNPs are in linkage disequilibrium (LD) with each other and represent one effect on impulsiveness. Four SNPs and the corresponding haplotype from intron 3 to intron 4 were also associated with Lifetime Alcohol Problems Score (LAPS, P < 0.03) (not corrected for multiple testing). Impulsiveness partially mediates (22.6% average) this relation between GABRA2 and LAPS. Our results suggest that GABRA2 variation in the region between introns 3 and 4 is associated with impulsiveness and this effect partially influences the development of alcohol problems, but a direct effect of GABRA2 on problem drinking remains. A potential functional SNP rs279827, located next to a splice site, is located in the most significant region for both impulsiveness and LAPS. The high degree of LD among nine of these SNPs and the conditional analyses we have performed suggest that all variants represent one signal .     

Evaluation of microsatellite markers in association studies: a search for an immune-related susceptibility gene in sarcoidosis

Association studies using linkage disequilibrium (LD) between candidate loci and nearby markers have been proposed to identify susceptibility genes for complex diseases. We analyzed polymorphisms of microsatellites (MSs) and LD patterns of the regions in which candidate genes related to the Th1 immune response have been annotated and attempted to identify a susceptibility gene for sarcoidosis in a marker-based association study. Nineteen MSs were identified in six Th1-related genes (IFNGR1, IFNGR2, IL12RB1, IL12RB2, STAT1 and STAT4) and then eight were further characterized as useful polymorphic markers. Most of these MSs showed LD with single nucleotide polymorphisms (SNPs) on both 5 and 3 ends of these candidate genes, in which r² values between at least one of the MS marker alleles and the SNPs were higher than 0.1. A significant association with one MS allele near STAT4 was shown and a cluster of SNPs in LD with the MS marker was associated with sarcoidosis. These results suggest that association studies using not only SNPs but also multi-allelic MS within or near candidate loci would be useful markers to search for a disease susceptibility gene, especially in populations with unknown LD structure.     

Using SNP markers to dissect linkage disequilibrium at a major quantitative trait locus for resistance to the potato cyst nematode Globodera pallida on potato chromosome V

The damage caused by the parasitic root cyst nematode Globodera pallida is a major yield-limiting factor in potato cultivation . Breeding for resistance is facilitated by the PCR-based marker ‘HC’, which is diagnostic for an allele conferring high resistance against G. pallida pathotype Pa2/3 that has been introgressed from the wild potato species Solanum vernei into the Solanum tuberosum tetraploid breeding pool. The major quantitative trait locus (QTL) controlling this nematode resistance maps on potato chromosome V in a hot spot for resistance to various pathogens including nematodes and the oomycete Phytophthora infestans. An unstructured sample of 79 tetraploid, highly heterozygous varieties and breeding clones was selected based on presence (41 genotypes) or absence (38 genotypes) of the HC marker. Testing the clones for resistance to G. pallida confirmed the diagnostic power of the HC marker. The 79 individuals were genotyped for 100 single nucleotide polymorphisms (SNPs) at 10 loci distributed over 38 cM on chromosome V. Forty-five SNPs at six loci spanning 2 cM in the interval between markers GP21-GP179 were associated with resistance to G. pallida. Based on linkage disequilibrium (LD) between SNP markers, six LD groups comprising between 2 and 18 SNPs were identified. The LD groups indicated the existence of multiple alleles at a single resistance locus or at several, physically linked resistance loci. LD group C comprising 18 SNPs corresponded to the ‘HC’ marker. LD group E included 16 SNPs and showed an association peak, which positioned one nematode resistance locus physically close to the R1 gene family. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Extent of mismatch between the period of circadian clocks and light/dark cycles determines time‐to‐emergence in fruit flies

Circadian clocks time developmental stages of fruit flies Drosophila melanogaster, while light/dark (LD) cycles delimit emergence of adults, conceding only during the “allowed gate.” Previous studies have revealed that time‐to‐emergence can be altered by mutations in the core clock gene period (per), or by altering the length of LD cycles. Since this evidence came from studies on genetically manipulated flies, or on flies maintained under LD cycles with limited range of periods, inferences that can be drawn are limited. Moreover, the extent of shortening or lengthening of time‐to‐emergence remains yet unknown. In order to pursue this further, we assayed time‐to‐emergence of D. melanogaster under 12 different LD cycles as well as in constant light (LL) and constant dark conditions (DD). Time‐to‐emergence in flies occurred earlier under LL than in LD cycles and DD. Among the LD cycles, time‐to‐emergence occurred earlier under T4–T8, followed by T36–T48, and then T12–T32, suggesting that egg‐to‐emergence duration in flies becomes shorter when the length of LD cycles deviates from 24 h, bearing a strong positive and a marginally negative correlation with day length, for values shorter and longer than 24 h, respectively. These results suggest that the extent of mismatch between the period of circadian clocks and environmental cycles determines the time‐to‐emergence in Drosophila.     

Association of SERPINE2 gene with the risk of chronic obstructive pulmonary disease and spirometric phenotypes in northern Han Chinese population

Chronic obstructive pulmonary disease (COPD) is a complex human disease influenced by multiple genes and environmental factors. The SERPINE2 gene has recently been demonstrated to be associated with COPD onset in a non-East Asian population. In this study, we genotyped 20 single nucleotide polymorphisms (SNPs) in SERPINE2 from 310 cases and 203 controls, all of which belong to the Han from North China. Genotype frequencies were compared between the cases and the controls and analyzed for statistical significance. Two SNPs (rs729631 and rs975278), which are in strong linkage disequilibrium (LD) and locate in block 1 on the LD map of our samples, showed significant association both with the risk of COPD and decline in baseline lung function after Bonferroni correction (P < 0.05). This study provides further evidences for SERPINE2 gene as a COPD susceptible gene, and block 1 of SERPINE2 appears to be the genetic variant region that affects the Han Chinese.     

Differential modes of crosslinking establish spatially distinct regions of peptidoglycan in Caulobacter crescentus

The diversity of cell shapes across the bacterial kingdom reflects evolutionary pressures that have produced physiologically important morphologies. While efforts have been made to understand the regulation of some prototypical cell morphologies such as that of rod‐shaped Escherichia coli, little is known about most cell shapes. For Caulobacter crescentus, polar stalk synthesis is tied to its dimorphic life cycle, and stalk elongation is regulated by phosphate availability. Based on the previous observation that C. crescentus stalks are lysozyme‐resistant, we compared the composition of the peptidoglycan cell wall of stalks and cell bodies and identified key differences in peptidoglycan crosslinking. Cell body peptidoglycan contained primarily DD‐crosslinks between meso‐diaminopimelic acid and D‐alanine residues, whereas stalk peptidoglycan had more LD‐transpeptidation (meso‐diaminopimelic acid‐meso‐diaminopimelic acid), mediated by LdtD. We determined that ldtD is dispensable for stalk elongation; rather, stalk LD‐transpeptidation reflects an aging process associated with low peptidoglycan turnover in the stalk. We also found that lysozyme resistance is a structural consequence of LD‐crosslinking. Despite no obvious selection pressure for LD‐crosslinking or lysozyme resistance in C. crescentus, the correlation between these two properties was maintained in other organisms, suggesting that DAP‐DAP crosslinking may be a general mechanism for regulating bacterial sensitivity to lysozyme.     

FastTagger: an efficient algorithm for genome-wide tag SNP selection using multi-marker linkage disequilibrium

Background  

Human genome contains millions of common single nucleotide polymorphisms (SNPs) and these SNPs play an important role in understanding the association between genetic variations and human diseases. Many SNPs show correlated genotypes, or linkage disequilibrium (LD), thus it is not necessary to genotype all SNPs for association study. Many algorithms have been developed to find a small subset of SNPs called tag SNPs that are sufficient to infer all the other SNPs. Algorithms based on the r ² LD statistic have gained popularity because r ² is directly related to statistical power to detect disease associations. Most of existing r ² based algorithms use pairwise LD. Recent studies show that multi-marker LD can help further reduce the number of tag SNPs. However, existing tag SNP selection algorithms based on multi-marker LD are both time-consuming and memory-consuming. They cannot work on chromosomes containing more than 100 k SNPs using length-3 tagging rules.