Alzheimer disease susceptibility loci: evidence for a protein network under natural selection

Recent genome-wide association studies have identified a number of susceptibility loci for Alzheimer disease (AD). To understand the functional consequences and potential interactions of the associated loci, we explored large-scale data sets interrogating the human genome for evidence of positive natural selection. Our findings provide significant evidence for signatures of recent positive selection acting on several haplotypes carrying AD susceptibility alleles; interestingly, the genes found in these selected haplotypes can be assembled, independently, into a molecular complex via a protein-protein interaction (PPI) network approach. These results suggest a possible coevolution of genes encoding physically-interacting proteins that underlie AD susceptibility and are coexpressed in different tissues. In particular, PICALM, BIN1, CD2AP, and EPHA1 are interconnected through multiple interacting proteins and appear to have coordinated evidence of selection in the same human population, suggesting that they may be involved in the execution of a shared molecular function. This observation may be AD-specific, as the 12 loci associated with Parkinson disease do not demonstrate excess evidence of natural selection. The context for selection is probably unrelated to AD itself; it is likely that these genes interact in another context, such as in immune cells, where we observe cis-regulatory effects at several of the selected AD loci.     

Evolutionary and Functional Analysis of Celiac Risk Loci Reveals SH2B3 as a Protective Factor against Bacterial Infection

Celiac disease (CD) is an intolerance to dietary proteins of wheat, barley, and rye. CD may have substantial morbidity, yet it is quite common with a prevalence of 1%–2% in Western populations. It is not clear why the CD phenotype is so prevalent despite its negative effects on human health, especially because appropriate treatment in the form of a gluten-free diet has only been available since the 1950s, when dietary gluten was discovered to be the triggering factor. The high prevalence of CD might suggest that genes underlying this disease may have been favored by the process of natural selection. We assessed signatures of selection for ten confirmed CD-associated loci in several genome-wide data sets, comprising 8154 controls from four European populations and 195 individuals from a North African population, by studying haplotype lengths via the integrated haplotype score (iHS) method. Consistent signs of positive selection for CD-associated derived alleles were observed in three loci: IL12A, IL18RAP, and SH2B3. For the SH2B3 risk allele, we also show a difference in allele frequency distribution (F_st) between HapMap phase II populations. Functional investigation of the effect of the SH2B3 genotype in response to lipopolysaccharide and muramyl dipeptide revealed that carriers of the SH2B3 rs3184504^∗A risk allele showed stronger activation of the NOD2 recognition pathway. This suggests that SH2B3 plays a role in protection against bacteria infection, and it provides a possible explanation for the selective sweep on SH2B3, which occurred sometime between 1200 and 1700 years ago.     

Recent advances in biosensors for diagnosis of celiac disease: A review

Celiac disease (CD) is an intestinal issue activated by the inappropriate immune reaction towards gluten protein of wheat, rye, barley, oats, and autoantigen, tissue transglutaminase. Regardless of the accessibility of immunochemical conventions for research facility analysis of CD, there is as yet a need of speedier, less expensive, and simpler devices for diagnosing CD. This review concentrates on progresses in biosensors for diagnosing CD in perspective of the scaled down hardware, multianalyte discovery and low sample volume necessity. Various recently developed biosensors in this field are presented.     

A high-density genetic recombination map of sequence-tagged sites for sorghum, as a framework for comparative structural and evolutionary genomics of tropical grains and grasses

We report a genetic recombination map for Sorghum of 2512 loci spaced at average 0.4 cM ( approximately 300 kb) intervals based on 2050 RFLP probes, including 865 heterologous probes that foster comparative genomics of Saccharum (sugarcane), Zea (maize), Oryza (rice), Pennisetum (millet, buffelgrass), the Triticeae (wheat, barley, oat, rye), and Arabidopsis. Mapped loci identify 61.5% of the recombination events in this progeny set and reveal strong positive crossover interference acting across intervals of 相似文献   

Patterns of polymorphism and linkage disequilibrium in cultivated barley

We carried out a genome-wide analysis of polymorphism (4,596 SNP loci across 190 elite cultivated accessions) chosen to represent the available genetic variation in current elite North West European and North American barley germplasm. Population sub-structure, patterns of diversity and linkage disequilibrium varied considerably across the seven barley chromosomes. Gene-rich and rarely recombining haplotype blocks that may represent up to 60% of the physical length of barley chromosomes extended across the ‘genetic centromeres’. By positioning 2,132 bi-parentally mapped SNP markers with minimum allele frequencies higher than 0.10 by association mapping, 87.3% were located to within 5 cM of their original genetic map position. We show that at this current marker density genetically diverse populations of relatively small size are sufficient to fine map simple traits, providing they are not strongly stratified within the sample, fall outside the genetic centromeres and population sub-structure is effectively controlled in the analysis. Our results have important implications for association mapping, positional cloning, physical mapping and practical plant breeding in barley and other major world cereals including wheat and rye that exhibit comparable genome and genetic features.     

A resistance gene analog useful for targeting disease resistance genes against different pathogens on group 1S chromosomes of barley,wheat and rye

Comparative sequence analysis of the resistance gene analog (RGA) marker locus aACT/CAA (originally found to be tightly linked to the multiallelic barley Mla cluster) from genomes of barley, wheat and rye revealed a high level of relatedness among one another and showed high similarity to a various number of NBS-LRR disease resistance proteins. Using the sequence-specific polymerase chain reaction (PCR), RGA marker aACT/CAA was mapped on group 1S chromosomes of the Triticeae and was associated with disease resistance loci. In barley and rye, the marker showed linkage to orthologous powdery mildew resistance genes Mla1 and Pm17, respectively, while in wheat linkage with a QTL against fusarium head blight (FHB) disease was determined. The use of RGA clones for R gene mapping and their role in the expression of qualitative and quantitative resistance is discussed.     

DNA condensation with polyamines. II. Electron microscopic studies

Approximately 75% of the wheat and rye genomes consist of repeated sequence DNA. Three-quarters of the non-repeated or few copy sequences in wheat are less than 1000 base-pairs long, whilst in rye approximately half of the non-repeated or few copy sequences are in this size class. Most of the remaining non-repeated or few copy sequences appear to be a few thousand base-pairs long.In this paper a somewhat novel approach has been used to quantitatively analyse the linear organisation of the large proportion of repeated sequence DNA as well as the non-repeated DNA in the wheat and rye genomes. Repeated sequences in the genomes of oats, barley, wheat and rye have been used as probes to distinguish and isolate four different groups of repeated sequences and their neighbouring sequences from the wheat and rye genomes. Radioactively labelled wheat or rye DNA fragments ranging from 200 to over 9000 nucleotides long were incubated separately with large excesses of denatured unlabelled oats, barley, wheat and rye DNAs to C_ot values which enable all the repeated sequences of the unlabelled DNA to renature. The following parameters were then determined from the proportions of total labelled DNA in fragments which had at least partially renatured. (1) The proportions of the repeated sequences in the labelled DNAs that were able to hybridise to each unlabelled DNA; (2) the mean distance apart of the hybridising sequences on the longer labelled fragments; and (3) the proportion of the genome in which the hybridising sequences were concentrated. Analysis of these results, together with those of separate experiments designed to quantitatively estimate the nature of sequences unable to reanneal with the repeated sequences of each of the probe DNAs, have enabled schematic maps to be drawn which show how the repeated and non-repeated sequences are arranged in the wheat and rye genomes.Both genomes are constructed from millions of relatively short sequences, most of them considerably shorter than 3000 base-pairs. This structure was recognised because adjacent sequences can be distinguished by their frequency of repetition (i.e. repeated or non-repeated) or by their evolutionary origin. Approximately 40 to 45% of the wheat genome and 30 to 35% of the rye genome consists of short non-repeated sequences interspersed between short repeated sequences. Approximately 50% of the wheat genome and 60% of the rye genome consists of tandemly arranged repeated sequences of different evolutionary origins. It is postulated that much of this complex repeated sequence DNA could have arisen from amplification of compound sequences, each containing repeated and non-repeated sequence DNA.Short repeated sequences with a number average length of around 200 base-pairs and which occupy about 20% of the wheat and rye genomes are related to repeated sequences also found in oats and barley. They are concentrated in 60 to 70% of the wheat and rye genomes, being interspersed with different short repeated sequences and a significant proportion of the short non-repeated sequences.Rye chromosomes contain more DNA than wheat chromosomes. This is principally, but not entirely, due to additional repeated sequence DNA. Many quantitative changes appear to have occurred in both genomes, possibly affecting most families of repeated sequences, since wheat and rye diverged from a common ancestor. Both species contain species-specific repeated sequences (24% of rye genome; 16% of wheat genome) but a large proportion of these are closely interspersed with repeated sequences found in both genomes.     

Towards a whole‐genome sequence for rye (Secale cereale L.)

We report on a whole‐genome draft sequence of rye (Secale cereale L.). Rye is a diploid Triticeae species closely related to wheat and barley, and an important crop for food and feed in Central and Eastern Europe. Through whole‐genome shotgun sequencing of the 7.9‐Gbp genome of the winter rye inbred line Lo7 we obtained a de novo assembly represented by 1.29 million scaffolds covering a total length of 2.8 Gbp. Our reference sequence represents nearly the entire low‐copy portion of the rye genome. This genome assembly was used to predict 27 784 rye gene models based on homology to sequenced grass genomes. Through resequencing of 10 rye inbred lines and one accession of the wild relative S. vavilovii, we discovered more than 90 million single nucleotide variants and short insertions/deletions in the rye genome. From these variants, we developed the high‐density Rye600k genotyping array with 600 843 markers, which enabled anchoring the sequence contigs along a high‐density genetic map and establishing a synteny‐based virtual gene order. Genotyping data were used to characterize the diversity of rye breeding pools and genetic resources, and to obtain a genome‐wide map of selection signals differentiating the divergent gene pools. This rye whole‐genome sequence closes a gap in Triticeae genome research, and will be highly valuable for comparative genomics, functional studies and genome‐based breeding in rye.     

A consensus linkage map of rye (Secale cereale L.) including 374 RFLPs, 24 isozymes and 15 gene loci

 Consensus linkage maps were constructed for all seven rye chromosomes using 12 basic RFLP maps. The maps presented contain a total of 413 markers. The number of markers per chromosome varies from 41 (chromosome 3R) to 83 (chromosome 1R). In addition to 374 RFLP and 24 isozyme markers 15 gene loci were incorporated, determining the traits reduced plant height, self fertility, male sterility restoration, vernalization response, resistance against powdery mildew, chlorophyll deficiency, hairy leaf sheath, hairy peduncle, waxy endosperm, waxless plant and absence of ligules. The maps presented allow the selection of markers for the fine mapping of certain regions of the rye genome. In terms of the known chromosomal rearrangements within the Triticeae its utilization can also be extended for mapping in wheat and barley. Received: 13 February 1998 / Accepted: 26 May 1998     

Molecular evolution of receptor-like kinase genes in hexaploid wheat. Independent evolution of orthologs after polyploidization and mechanisms of local rearrangements at paralogous loci

Hexaploid wheat is a young polyploid species and represents a good model to study mechanisms of gene evolution after polyploidization. Recent studies at the scale of the whole genome have suggested rapid genomic changes after polyploidization but so far the rearrangements that have occurred in terms of gene content and organization have not been analyzed at the microlevel in wheat. Here, we have isolated members of a receptor kinase (Lrk) gene family in hexaploid and diploid wheat, Aegilops tauschii, and barley (Hordeum vulgare). Phylogenetic analysis has allowed us to establish evolutionary relationships (orthology versus paralogy) between the different members of this gene family in wheat as well as with Lrk genes from barley. It also demonstrated that the sequences of the homoeologous Lrk genes evolved independently after polyploidization. In addition, we found evidence for gene loss during the evolution of wheat and barley. Analysis of large genomic fragments isolated from nonorthologous Lrk loci showed a high conservation of the gene content and gene organization at these loci on the homoeologous group 1 chromosomes of wheat and barley. Finally, sequence comparison of two paralogous fragments of chromosome 1B showed a large number of local events (sequence duplications, deletions, and insertions), which reveal rearrangements and mechanisms for genome enlargement at the microlevel.     

Comparative molecular-genetic mapping of genomes of rye (Secale cereale L.) and other cereals

The genetic map of rye consisting of 149 RFLP, 20 isozyme and 12 microsatellite markers was developed. Using the collection of cross-hybridizing probes, the presence of multiple translocations in rye genome with respect to wheat and barley genomes was shown. However, within large regions of genome a strict collinearity of marker order was observed that allow us to use the method of comparative mapping for an introduction of new genes. In the developed genetic map 18 morphological and breeding-valuable genes mapped in different rye populations were integrated. The comparative analysis of homeological loci in genomes of Triticeae species as well as in genomes of rice and maize was carried out. The genes controlling a number of morphological traits, plant height, photoperiodic response and winter/spring growth habit were shown to be conserve among cereals and to form clear homoeologous rows.     

On the distribution of temporal variations in allele frequency: consequences for the estimation of effective population size and the detection of loci undergoing selection

The effective population size (Ne) is frequently estimated using temporal changes in allele frequencies at neutral markers. Such temporal changes in allele frequencies are usually estimated from the standardized variance in allele frequencies (Fc). We simulate Wright-Fisher populations to generate expected distributions of Fc and of Fc (Fc averaged over several loci). We explore the adjustment of these simulated Fc distributions to a chi-square distribution and evaluate the resulting precision on the estimation of Ne for various scenarios. Next, we outline a procedure to test for the homogeneity of the individual Fc across loci and identify markers exhibiting extreme Fc-values compared to the rest of the genome. Such loci are likely to be in genomic areas undergoing selection, driving Fc to values greater (or smaller) than expected under drift alone. Our procedure assigns a P-value to each locus under the null hypothesis (drift is homogeneous throughout the genome) and simultaneously controls the rate of false positive among loci declared as departing significantly from the null. The procedure is illustrated using two published data sets: (i) an experimental wheat population subject to natural selection and (ii) a maize population undergoing recurrent selection.     

Molecular and cytological characterization of genomic variability in hexaploid wheat 'Lindstr?m'.

'Lindstr?m' wheat (AABBDD+rye B chromosomes) was used to study the effects of alien chromatin introgressed into a wheat genetic background, subjecting the wheat genome to a new and transient allopolyploidisation episode. Using this experimental material, we have previously demonstrated that no large-scale chromosomal translocations occurred as a result of the genomic constitution of the addition line. However, we have shown that the presence of a number of rye B chromosomes is associated with changes in the interphase organization and expression patterns of wheat rDNA loci. We have now extended our studies to focus on a further characterization of 'Lindstr?m' 5S rDNA loci and also on high molecular weight glutenin subunit (HMW-GS) patterns. In the process, we have uncovered an unusually large variant of the 5S rDNA locus on wheat chromosome 1B (not to be confused with rye B chromosomes) and 2 novel HMW glutenin y-type alleles. These changes are not directly related to variation in rye B chromosome number in the present material, but the fact that a new, and still segregating, 1Dy HMW-GS gene was identified indicates a recent timescale for its origin. Strikingly, the 'Lindstr?m' 5S rDNA 1B locus integrates a unit sharing 94% homology with a rye 5S rDNA sequence, suggesting the possibility that the wheat locus was colonized by highly homologous rye sequences during the breeding of 'Lindstr?m', when the rye and wheat genomes were together, albeit briefly, in the same nucleus.     

BIS 1, a major component of the cereal genome and a tool for studying genomic organization

We report the cloning and characterization of an element (BIS 1) in barley. Related sequences were also found in wheat and rye genomes. BIS 1-related sequences may be some of the more frequent of the complex repeats in the barley genome, and their dispersion throughout the barley genome suggests that they are capable of both mobility and amplification. BIS 1 sequences have been used to study the gross structure of the barley genome. These studies indicate that the genome may be formed from larger genomic structures of tens of kilobases which may be repeated. Surprisingly, these studies also show that these large genomic structures also occur in similar proportions and at similar size distribution in the wheat genome.     

RFLP-based mapping of three mutant loci in rye (Secale cereale L.) and their relation to homoeologous loci within the Gramineae

 Three mutant loci of rye determining absence of ligules (al), waxless plant (wa1) and waxy endosperm (Wx) characters were mapped in a single F₂ population, comprising 84 individual plants. The three loci could be clearly tagged in relation to 7 (al on chromosome 2R), 4 (wa1 on chromosome 7R) or 6 (Wx on chromosome 4R) RFLP markers. The mapping data are compared with existing data for homoeologous regions containing equivalent mutants of wheat, barley, rice and maize. It is shown that the loci analysed are highly conserved across the cereal species, including rye. Received: 14 March 1997 / Accepted: 21 March 1997     

Genomic signatures of local adaptation in the Drosophila immune response

As environments and pathogen landscapes shift, host defenses must evolve to remain effective. Due to this selection pressure, among-species comparisons of genetic sequence data often find immune genes to be among the fastest evolving genes across the genome. The full extent and nature of these immune adaptations, however, remain largely unexplored. In a recent study, we analyzed patterns of selection within distinct components of the Drosophila melanogaster immune pathway. While we found evidence of positive selection within some immune processes, immune genes were not universally characterized by signatures of strong selection. On the contrary, we even found that some immune functions show greater than expected constraint. Overall these results highlight 2 major factors that appear to play an outsize role in determining a gene's evolutionary rate: the type of pathogen the gene targets and the gene's position within the immune network. These results join a growing body of literature that highlight the complexity of immune adaptation. Rather than there being uniformly strong selection across all immune genes, a combination of pathogen-specificity and host genetic constraints appear to play key roles in determining each immune gene's individual evolutionary trajectory.     

Barley Cbf3 gene identification,expression pattern,and map location

Although cold and drought adaptation in cereals and other plants involve the induction of a large number of genes, inheritance studies in Triticeae (wheat [Triticum aestivum], barley [Hordeum vulgare], and rye [Secale cereale]) have revealed only a few major loci for frost or drought tolerance that are consistent across multiple genetic backgrounds and environments. One might imagine that these loci could encode highly conserved regulatory factors that have global effects on gene expression; therefore, genes encoding central regulators identified in other plants might be orthologs of these Triticeae stress tolerance genes. The CBF/DREB1 regulators, identified originally in Arabidopsis as key components of cold and drought regulation, merit this consideration. We constructed barley cDNA libraries, screened these libraries and a barley bacterial artificial chromosome library using rice (Oryza sativa) and barley Cbf probes, found orthologs of Arabidopsis CBF/DREB1 genes, and examined the expression and genetic map location of the barley Cbf3 gene, HvCbf3. HvCbf3 was induced by a chilling treatment. HvCbf3 is located on barley chromosome 5H between markers WG364b and saflp58 on the barley cv Dicktoo x barley cv Morex genetic linkage map. This position is some 40 to 50 cM proximal to the winter hardiness quantitative trait locus that includes the Vrn-1H gene, but may coincide with the wheat 5A Rcg1 locus, which governs the threshold temperature at which cor genes are induced. From this, it remains possible that HvCbf3 is the basis of a minor quantitative trait locus in some genetic backgrounds, though that possibility remains to be thoroughly explored.     

A genetic linkage map of rye (Secale cereale L.)

 A genetic linkage map of rye composed of 91 loci (88 RFLP, two morphological and one isozyme markers) has been developed using two reciprocal crosses. The RFLP loci covering all seven chromosomes were detected by a selection of rye, wheat, barley and oat cDNA and genomic DNA probes. The level of polymorphism was dependent on the source of the clones, with a ranking of rye>wheat>barley>oat. Distorted segregations were detected in linkage groups of chromosomes 1R, 4R, 5R and 7R. When the recombination of the two reciprocal crosses was compared, no systematic increase or decrease in one or the other direction was observed suggesting that a combination of populations of reciprocal crosses is possible. Received: 5 August 1997/Accepted: 2 September 1997