Some notes on the combinatorial properties of haplotype tagging

Tagging haplotypes with a small number of genetic markers is becoming an increasingly interesting and important problem. Surprisingly little work has been done to characterize the mathematical framework of this problem. In this paper we present a mathematical frame, based on Boolean algebras, that adequately describe the structure of a set of genetic bi-allelic markers and the corresponding set of haplotypes. We derive a number of results that relate the number of markers required to tag a set of haplotypes to the set of markers themselves.     

SNP haplotype tagging from DNA pools of two individuals

Background  

DNA pooling is a technique to reduce genotyping effort while incurring only minor losses in accuracy of allele frequency estimates for single nucleotide polymorphism (SNP) markers.     

Finding haplotype tagging SNPs by use of principal components analysis

The immense volume and rapid growth of human genomic data, especially single nucleotide polymorphisms (SNPs), present special challenges for both biomedical researchers and automatic algorithms. One such challenge is to select an optimal subset of SNPs, commonly referred as "haplotype tagging SNPs" (htSNPs), to capture most of the haplotype diversity of each haplotype block or gene-specific region. This information-reduction process facilitates cost-effective genotyping and, subsequently, genotype-phenotype association studies. It also has implications for assessing the risk of identifying research subjects on the basis of SNP information deposited in public domain databases. We have investigated methods for selecting htSNPs by use of principal components analysis (PCA). These methods first identify eigenSNPs and then map them to actual SNPs. We evaluated two mapping strategies, greedy discard and varimax rotation, by assessing the ability of the selected htSNPs to reconstruct genotypes of non-htSNPs. We also compared these methods with two other htSNP finders, one of which is PCA based. We applied these methods to three experimental data sets and found that the PCA-based methods tend to select the smallest set of htSNPs to achieve a 90% reconstruction precision.     

Marked differences of haplotype tagging SNP distribution,linkage, and haplotype profile of IL23 receptor gene in Roma and Hungarian population samples

Polymorphisms of the interleukin-23 receptor (IL23R) gene have been found to play an important role in the development of several autoimmune diseases. We examined five susceptible (rs10889677, rs1004819, rs2201841, rs11805303, rs11209032), one protective (rs7517847) and two neutral variants (rs7530511, rs1884444) of the IL23R gene in pooled DNA of healthy Roma (Gipsy) and Hungarian population samples. Our aim was to determine the genetic variability of the major haplotype tagging polymorphisms, and the haplotype profile of IL23R between the two groups. We analyzed 273 healthy Roma and 253 Hungarian DNA samples using PCR/RFLP assay. Comparing the five susceptible conferring alleles, there were significant increase (p < 0.05), while in the protective alleles, there were decrease in the allele frequencies in Roma population (p < 0.05). One of the neutral alleles showed increase, the another one did not differ between the two groups. The haplotype analysis of the SNPs revealed fundamentally different association types of SNPs in the two groups; moreover, the frequencies of the various haplotypes also exhibited strong differences, as of ht4 and ht5 haplotypes were significantly higher, whereas the frequencies of ht2 and ht3 haplotypes were significantly lower in the Roma population than in Hungarians (p < 0.05). The data presented here show profound differences in the IL23R genetic profiles in the Roma population, that likely has also clinical implications in respect their possible role in the development of certain immunological diseases.     

Fragment tagging

A tactic known as fragment tagging, which has proven to be exceptionally useful in expediting DNA cloning and plasmid construction schemes, is described. The advantage of fragment tagging is that it facilitates the isolation of specific plasmid DNA molecules present in small amounts within mixed pools of DNA. Four examples that illustrate several variations of the fragment tagging concept are presented.     

Fragment tagging

A tactic known as fragment tagging, which has proven to be exceptionally useful in expediting DNA cloning and plasmid construction schemes, is described. The advantage of fragment tagging is that it facilitates the isolation of specific plasmid DNA molecules present in small amounts within mixed pools of DNA. Four examples that illustrates several variations of the fragment tagging concept are presented.     

Epitope tagging

Epitope tagging is widely used in the characterization of newly discovered proteins. This review presents an overview of how the technique evolved and how it is being used today, with a focus on its use in the study of protein-protein interactions. In addition, the evolution of the technique for proteomic analyses is described.     

植物基因工程中的转座子标签

195 1年ＢａｒｂａｒａＭｃｌｉｎｔｏｃｋ首先在玉米中发现了控制元件 ,后来命名为转座元件或转座子 (ｔｒａｎｓｐｏｓｏｎ)。转座子是基因组中一段可移动的ＤＮＡ序列 ,可以通过切割、重新整合等一系列过程从基因组的一个位置“跳跃”到另一个位置。这一元件不仅可用于分析生物遗传进化上分子作用引起的一些现象 ,还为基因工程和分子生物学研究提供了强有力的工具 ,可以在不了解基因产物的生化性质和表达模式的情况下 ,分离克隆植物基因 ,即转座子标签 (ｔｒａｎｓｐｏｓｏｎｔａｇｇｉｎｇ) ,又称为转座子示踪法。其原理是利用转座子的…     

Enzyme-mediated tagging of RNA

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Beyond Rf tagging

The split-pool diversity orientated synthesis method, which requires some form of encoding to track the synthesis of discrete compounds, has been the lynchpin of most combinatorial synthesis efforts. The use of encoding methods in combinatorial chemistry has matured, and depending on their level of resources, chemists now have a diverse choice of encoding methods available. New methods of encoding have been developed that are inexpensive, simple to incorporate into any laboratory, and utilize analytical equipment such as MS, FTIR and NMR that are readily available to most organic chemists.     

N-azidoacetylmannosamine-mediated chemical tagging of gangliosides

Peracetylated N-alpha-azidoacetylmannosamine (Ac(4)ManNAz) is metabolized by cells to CMP-azidosialic acid. It has been demonstrated previously that in this way azidosialic acid-containing glycoproteins are formed that can be labeled on the cell surface by a modified Staudinger ligation. Here, we first demonstrate that the same procedure also results in the formation of azidosialic acid-containing gangliosides. Deoxymannojirimycin, an inhibitor of N-glycan processing in proteins, decreases the total cell surface labeling in Jurkat cells by approximately 25%. Inhibition of ganglioside biosynthesis with N-[5-(adamantan-1-yl-methoxy)-pentyl]1-deoxynojirimycin reduces cell surface labeling by approximately 75%. In conclusion, exposure of cells to Ac(4)ManNAz allows in vivo chemical tagging of gangliosides.     

The histopathology of salmon tagging

Histopathological studies were carried out on the pathogenesis of the lesion induced by the insertion of a light plastic identification tag, in salmon parr on the river North Esk, Scotland. The experiments were carried out at mean water temperature of 127deg;C, 8°C and 4°C. The inflammatory response was similar at each temperature, but the rate of its development was markedly inhibited at 4°C. The qualitative response at the lower temperature was also slightly different in that polymorphonuclear leukocytes appeared to play a slightly more dominant role and the connective tissue response, which in all cases outweighed myofibrillar regeneration was more cellular at that temperature. The tagging lesion provides a very suitable model for the study of short and long term inflammation in salmonids and studies on the modification of these defensive mechanisms by temperature.     

The histopathology of salmon tagging

Hatchery reared Atlantic salmon ( Salmo salar L.) parr were tagged with the standard I.C.E.S./I.C.N.A.F. salmon tag at water temperatures of 15°C and 6°C. They were then subjected to swimming trials in a tunnel respirometer. Following this treatment the 15°C fish developed necrotic infarcts around the tag insertions. Provided they did not become infected these lesions healed, but if the fish were retested 9 days later, the wound enlarged, became extremely inflamed, and the fish died soon after. This effect was not seen in 6°C fish.     

Transposon tagging in rice

To develop an efficient gene isolation method for rice we introduced the maize Ac/Ds system into rice. Extensive analysis of their behavior in rice for several generations indicated that Ac and Ds in the presence of Ac transposase gene actively transpose in rice. A wide spectrum of mutations affecting growth, morphogenesis, flowering time and disease resistance have been obtained in the population carrying Ac/Ds and some of them were genetically analyzed. Main efforts are currently being made to isolate genes responsible these mutations. In addition, a number of Ac/Ds were mapped on chromosomes and mapped elements will be used in the future for directed tagging of genes with known chromosomal positions.     

Transposon tagging in maize

Through recent government- and industry-sponsored efforts, several forward and reverse genetic screening programs have emerged over the past few years to aid in the genetic dissection of gene function in maize. Despite a US maize crop valued at $18.4 billion last year (http://www.ncga.com/03world/main/US_crop_value_2000.html) and rich genetic history, maize has taken a back seat to Arabidopsis thaliana as the model genetic system for plants over the past decade. With a fully sequenced genome, short generation time and small size, studies of Arabidopsis have provided plant scientists with a molecular framework for hormonal, developmental and environmental signaling pathways in plants. As investigations into Arabidopsis continue, our capacity to engineer biochemical pathways and alter plant physiological responses will become increasingly sophisticated. Nevertheless, approximately 130 million years have passed since monocot and higher eudicot lineages diverged. Thus, our ability to engineer agronomically important monocot grasses such as maize, rice and wheat will become increasingly limited by our lack of understanding of the physiological and morphological differences that have evolved in the monocots and higher eudicots. The sophisticated transposon collections now being generated for maize are but one of several recent projects (http://www.nsf.gov/bio/pubs/awards/genome01.htm) to provide grass researchers with essential tools for genome analysis. Because grain crops are such a closely related group, it is hoped that many of the findings made in one grass will be directly applicable to understanding the biology of another. The goal of this review is to highlight the recent developments in maize transposon-based gene characterization programs and provide a critical examination of the advantages and disadvantages each system offers. Electronic Publication