Localisation of Plasmodium falciparum uroporphyrinogen III decarboxylase of the heme-biosynthetic pathway in the apicoplast and characterisation of its catalytic properties

Uroporphyrinogen decarboxylase (UROD) is a key enzyme in the heme-biosynthetic pathway and in Plasmodium falciparum it occupies a strategic position in the proposed hybrid pathway for heme biosynthesis involving shuttling of intermediates between different subcellular compartments in the parasite. In the present study, we demonstrate that an N-terminally truncated recombinant P. falciparum UROD (r(Δ)PfUROD) over-expressed and purified from Escherichia coli cells, as well as the native enzyme from the parasite were catalytically less efficient compared with the host enzyme, although they were similar in other enzyme parameters. Molecular modeling of PfUROD based on the known crystal structure of the human enzyme indicated that the protein manifests a distorted triose phosphate isomerase (TIM) barrel fold which is conserved in all the known structures of UROD. The parasite enzyme shares all the conserved or invariant amino acid residues at the active and substrate binding sites, but is rich in lysine residues compared with the host enzyme. Mutation of specific lysine residues corresponding to residues at the dimer interface in human UROD enhanced the catalytic efficiency of the enzyme and dimer stability indicating that the lysine rich nature and weak dimer interface of the wild-type PfUROD could be responsible for its low catalytic efficiency. PfUROD was localised to the apicoplast, indicating the requirement of additional mechanisms for transport of the product coproporphyrinogen to other subcellular sites for its further conversion and ultimate heme formation.

The Roman Republican Navy : from the sixth century to 167 BC

Työ käsittelee Rooman laivaston kehitystä, toimintaa ja osallistumista laajenemispolitiikkaan, jossa Rooma kasvoi kaupunkivaltiosta Välimeren hallitsijaksi. Rooma on aikaisemmissa tutkimuksissa nähty maavaltiona vailla kiinnostusta merenkulkuun. On katsottu, että ainoa merkittävä merisota Rooman historiassa on ensimmäinen puunilaissota (264-241 eKr.) ja että siinäkin roomalaiset (jotka historioitsija Polybius kuvaa vasta-alkajiksi) menestyivät Karthagoa vastaan turvautumalla laskusiltoihin, joiden avulla he saattoivat muuttaa meritaistelun maataisteluksi. Polybiuksen kuvaukseen on aina tähän asti luotettu. On katsottu että Roomalla ei ollut laivastoa ennen ensimmäistä puunilaissotaa ja että Rooma kaikissa sodissaan panosti merisodankäyntiin mahdollisimman vähän. Tämä työ pyrkii kumoamaan nämä käsitykset. Laivasto oli osallisena ja ehdottoman välttämätön kaikissa Rooman laajenemispolitiikan käänteissä. Arkeologian tiedot osoittavat, että ennen ensimmäistä puunilaissotaa Rooma kehittyi ja siitä tuli merkittävä kaupunki nimenomaan kaupankäynnin ja ulkomaisten kontaktien seurauksena. Se ei siis ollut puhdas agraarivaltio. Roomalaisilla oli laivasto jo viimeistään 500-luvulta lähtien eKr. ja sitä käytettiin Rooman laajentaessa valtaansa Italiassa. Näin ollen ensimmäisessä puunilaissodassa läntisen Välimeren herruudesta kilpaili kaksi merivaltiota, Rooma ja Karthago. Toinen puunilaissota (218-201) tunnetaan yleensä Hannibalin tulosta Alppien yli Italiaan, mutta se oli myöskin merkittävä merisota ja karthagolaiset hävisivät sen nimenomaan merellä. Rooma osallistui kilpailuun itäisen Välimeren hallinnasta ja kukisti Makedonian ja Syyrian laivastot, jotka eivät olleet mitenkään Rooman laivaston veroisia. Kaikista Rooman vastustajista Karthagolla olisi ollut suurin mahdollisuus pysäyttää Rooman laivaston voittokulu toisessa puunilaissodassa. Laivastoa käytettiin moniin eri tarkoituksiin. Suuret meritaistelut eivät ole ainoa osoitus laivastojen mukanaolosta ja merkityksestä, vaan on myös otettava huomion sotalaivojen rakenne ja toimintaedellytykset. Sotalaivat oli rakennettu taisteluita varten ja niissä oli hyvin niukasti säilytystilaa. Niiden oli päästävä laskemaan maihin aina kun miehistö tarvitsi vettä, ruokaa ja lepoa. Laivastot saattoivat toimia vain niiden rannikoiden tuntumassa, joiden satamiin ja laskupaikkoihin niillä oli turvallinen pääsy. Roomalaiset olivat hyvin tietoisia tästä. Suuret merentakaiset sotaretket Afrikkaan, Espanjaan, Kreikkaan ja Vähän-Aasian rannikolle perustuivat kaikki siihen, että Rooman laivasto hallitsi purjehdusreittejä ja sopivia laskupaikkoja ja saattoi huolehtia joukkojen ja varusteiden kuljettamisesta kaukana taisteleville armeijoille. Samalla Rooman laivasto kävi itsenäistä sotaa merellä ja haastoi ja kukisti kaikki Välimeren merivaltiot. 130-luvulle eKr. tultaessa se oli lyönyt vihollisensa ja riisunut aseista liittolaisensa; Rooman laivasto hallitsi Välimerta yksin.

Other Side of This Life : Death, Value, and Social Being in Thomas Pynchon's Fiction

This dissertation analyzes the interrelationship between death, the conditions of (wo)man s social being, and the notion of value as it emerges in the fiction of the American novelist Thomas Pynchon (1937 ). Pynchon s present work includes six novels V. (1963), The Crying of Lot 49 (1966), Gravity s Rainbow (1973), Vineland (1990), Mason & Dixon (1997), Against the Day (2006) and several short stories. Death constitues a central thematic in Pynchon s work, and it emerges through recurrent questions of mortality, suicide, mass destruction, sacrifice, afterlife, entropy, the relationship between the animate and the inanimate, and the limits of representation. In Pynchon, death is never a mere biological given (or event); it is always determined within a certain historical, cultural, and ideological context. Throughout his work, Pynchon questions the strict ontological separation of life and death by showing the relationship between this separation and social power. Conceptual divisions also reflect the relationship between society and its others, and death becomes that through which lines of social demarcation are articulated. Determined as a conceptual and social "other side", death in Pynchon forms a challenge to modern culture, and makes an unexpected return: the dead return to haunt the living, the inanimate and the animate fuse, and technoscientific attempts at overcoming and controlling death result in its re-emergence in mass destruction and ecological damage. The questioning of the ontological line also affects the structuration of Pynchon's prose, where the recurrent narrated and narrative desire to reach the limits of representation is openly associated with death. Textualized, death appears in Pynchon's writing as a sudden rupture within the textual functioning, when the "other side", that is, the bare materiality of the signifier is foregrounded. In this study, Pynchon s cultural criticism and his poetics come together, and I analyze the subversive role of death in his fiction through Jean Baudrillard s genealogy of the modern notion of death from L échange symbolique et la mort (1976). Baudrillard sees an intrinsic bond between the social repression of death in modernity and the emergence of modern political economy, and in his analysis economy and language appear as parallel systems for generating value (exchange value/ sign-value). For Baudrillard, the modern notion of death as negativity in relation to the positivity of life, and the fact that death cannot be given a proper meaning, betray an antagonistic relation between death and the notion of value. As a mode of negativity (that is, non-value), death becomes a moment of rupture in relation to value-based thinking in short, rationalism. Through this rupture emerges a form of thinking Baudrillard labels the symbolic, characterized by ambivalence and the subversion of conceptual opposites.

Role of Diadegma semiclausum (Hymenoptera: Ichneumonidae) in controlling Plutella xylostella (Lepidoptera: Plutellidae): Cage exclusion experiments and direct observation

We evaluated the role of the larval parasitoid, Diadegma semiclausum Hellén (Hymenoptera: Ichneumonidae), in controlling Plutella xylostella (L.) (Lepidoptera: Plutellidae) by cage exclusion experiments and direct field observation during the winter season in southern Queensland, Australia. The cage exclusion experiment involved uncaged, open cage and closed cage treatments. A higher percentage (54-83%) of P. xylostella larvae on sentinel plants were lost in the uncaged treatment than the closed (4-9%) or open cage treatments (11-29%). Of the larvae that remained in the uncaged treatment, 72-94% were parasitized by D. semiclausum, much higher than that in the open cage treatment (8-37% in first trial, and 38-63% in second trial). Direct observations showed a significant aggregation response of the field D. semiclausum populations to high host density plants in an experimental plot and to high host density plots that were artificially set-up near to the parasitoid source fields. The degree of aggregation varied in response to habitat quality of the parasitoid source field and scales of the manipulated host patches. As a result, density-dependence in the pattern of parasitism may depend on the relative degree of aggregation of the parasitoid population at a particular scale. A high degree of aggregation seems to be necessary to generate density-dependent parasitism by D. semiclausum. Integration of the cage exclusion experiment and direct observation demonstrated the active and dominant role of this parasitoid in controlling P. xylostella in the winter season. A biologically based IPM strategy, which incorporates the use of D. semiclausum with Bt, is suggested for the management of P. xylostella in seasons or regions with a mild temperature.

Makt, konst, elit - konstfältets positioner, relationer och resurser i 1940- och 1950-talens Helsingfors

The dissertation examines the power mechanisms and institutional power hierarchies of the 1940s-1950s era arts elite in Helsinki and their influence on issues of taste in the visual arts. For the purposes of this study, the elite is understood to consist mainly of the board members of the principal elected bodies in the field of the arts. The theoretical framework employed is based on Pierre Bourdieu s field theory and the network perspective. The author has examined what the key, pervasive valuations were that governed the exercising of power by the arts elite in issues of taste, involving determination of who was an acknowledged artist and what was good art. The dissertation demonstrates that this exercising of power was governed by certain collective practices which maintained the illusion that the exercising of power was democratic and based on artistic quality. These practices were the corporate system, using artistic arguments in issues of taste, and using networks in the exercising of power. The struggle in the field of the arts was about who ultimately was entitled to define the value of contemporary art; the issue did not arise regarding historical art. Artists managed to gain a leading position as gatekeepers in issues regarding contemporary art. The author discusses a number of conflicts in the field of the arts that highlight the institutional hierarchies and the capital held by the various players. The structural changes that occurred in administration in the field of cultural production in the 1950s led to the separation of bureaucratic competence on the one hand and aesthetic competence on the other. There was a hierarchy in the field of the arts between institutions, between instruments of legitimisation, and between the symbolic and social capital of players in the field. The hierarchy in the arts ultimately depended on how well the elite could influence tastes through the instruments at their disposal. The various instruments of legitimisation grants, purchases, etc. were ranked differently in the evaluation of acknowledged artists and good art. The dissertation discusses what values, in the form of types of symbolic capital, the arts elite embraced and what role these played in the elite s exercising of power, with particular focus on gender, language, region and economic capital. The aesthetic capital of an artist was of only minor importance in the exercising of power by the arts elite. The dissertation further discusses the points of contact between the arts elite and players in other fields, such as the economic, media and consumer fields. When the arts elite, through the Academy of Fine Arts, became an active player in the art market, this led to a hierarchy where the division between acknowledged and not-acknowledged galleries became sharper.

ShadowBoxer and LocusEater: programs to optimise experimental design and multiplexing strategies for genetic mark-recapture

Genetic mark–recapture requires efficient methods of uniquely identifying individuals. 'Shadows' (individuals with the same genotype at the selected loci) become more likely with increasing sample size, and bias harvest rate estimates. Finding loci is costly, but better loci reduce analysis costs and improve power. Optimal microsatellite panels minimize shadows, but panel design is a complex optimization process. locuseater and shadowboxer permit power and cost analysis of this process and automate some aspects, by simulating the entire experiment from panel design to harvest rate estimation.

Self-rating scales in the assessment of current and childhood symptoms of attention deficit hyperactivity disorder in adults

Objective: Attention deficit hyperactivity disorder (ADHD) is a life-long condition, but because of its historical status as a self-remitting disorder of childhood, empirically validated and reliable methods for the assessment of adults are scarce. In this study, the validity and reliability of the Wender Utah Rating Scale (WURS) and the Adult Problem Questionnaire (APQ), which survey childhood and current symptoms of ADHD, respectively, were studied in a Finnish sample. Methods: The self-rating scales were administered to adults with an ADHD diagnosis (n = 38), healthy control participants (n = 41), and adults diagnosed with dyslexia (n = 37). Items of the self-rating scales were subjected to factor analyses, after which the reliability and discriminatory power of the subscales, derived from the factors, were examined. The effects of group and gender on the subscales of both rating scales were studied. Additionally, the effect of age on the subscales of the WURS was investigated. Finally, the diagnostic accuracy of the total scores was studied. Results: On the basis of the factor analyses, a four-factor structure for the WURS and five-factor structure for the APQ had the best fit to the data. All of the subscales of the APQ and three of the WURS achieved sufficient reliability. The ADHD group had the highest scores on all of the subscales of the APQ, whereas two of the subscales of the WURS did not statistically differ between the ADHD and the Dyslexia group. None of the subscales of the WURS or the APQ was associated with the participant's gender. However, one subscale of the WURS describing dysthymia was positively correlated with the participant's age. With the WURS, the probability of a correct positive classification was .59 in the current sample and .21 when the relatively low prevalence of adult ADHD was taken into account. The probabilities of correct positive classifications with the APQ were .71 and .23, respectively. Conclusions: The WURS and the APQ can provide accurate and reliable information of childhood and adult ADHD symptoms, given some important constraints. Classifications made on the basis of the total scores are reliable predictors of ADHD diagnosis only in populations with a high proportion of ADHD and a low proportion of other similar disorders. The subscale scores can provide detailed information of an individual's symptoms if the characteristics and limitations of each domain are taken into account. Improvements are suggested for two subscales of the WURS.

Traffic safety at road–rail level crossings using a driving simulator and traffic simulation

Several intelligent transportation systems (ITS) were used with an advanced driving simulator to assess its influence on driving behavior. Three types of ITS interventions were tested: video in vehicle, audio in vehicle, and on-road flashing marker. The results from the driving simulator were inputs for a developed model that used traffic microsimulation (VISSIM 5.4) to assess the safety interventions. Using a driving simulator, 58 participants were required to drive through active and passive crossings with and without an ITS device and in the presence or absence of an approaching train. The effect of changes in driver speed and compliance rate was greater at passive crossings than at active crossings. The slight difference in speed of drivers approaching ITS devices indicated that ITS helped drivers encounter crossings in a safer way. Since the traffic simulation was not able to replicate a dynamic speed change or a probability of stopping that varied depending on ITS safety devices, some modifications were made to the traffic simulation. The results showed that exposure to ITS devices at active crossings did not influence drivers’ behavior significantly according to the traffic performance indicator, such as delay time, number of stops, speed, and stopped delay. However, the results of traffic simulation for passive crossings, where low traffic volumes and low train headway normally occur, showed that ITS devices improved overall traffic performance.

Measuring and predicting canopy nitrogen nutrition in wheat using a spectral index—The canopy chlorophyll content index (CCCI).

Varying the spatial distribution of applied nitrogen (N) fertilizer to match demand in crops has been shown to increase profits in Australia. Better matching the timing of N inputs to plant requirements has been shown to improve nitrogen use efficiency and crop yields and could reduce nitrous oxide emissions from broad acre grains. Farmers in the wheat production area of south eastern Australia are increasingly splitting N application with the second timing applied at stem elongation (Zadoks 30). Spectral indices have shown the ability to detect crop canopy N status but a robust method using a consistent calibration that functions across seasons has been lacking. One spectral index, the canopy chlorophyll content index (CCCI) designed to detect canopy N using three wavebands along the "red edge" of the spectrum was combined with the canopy nitrogen index (CNI), which was developed to normalize for crop biomass and correct for the N dilution effect of crop canopies. The CCCI-CNI index approach was applied to a 3-year study to develop a single calibration derived from a wheat crop sown in research plots near Horsham, Victoria, Australia. The index was able to predict canopy N (g m-2) from Zadoks 14-37 with an r2 of 0.97 and RMSE of 0.65 g N m-2 when dry weight biomass by area was also considered. We suggest that measures of N estimated from remote methods use N per unit area as the metric and that reference directly to canopy %N is not an appropriate method for estimating plant concentration without first accounting for the N dilution effect. This approach provides a link to crop development rather than creating a purely numerical relationship. The sole biophysical input, biomass, is challenging to quantify robustly via spectral methods. Combining remote sensing with crop modelling could provide a robust method for estimating biomass and therefore a method to estimate canopy N remotely. Future research will explore this and the use of active and passive sensor technologies for use in precision farming for targeted N management.

High resolution satellite imagery and GPS collars can help assist in the assessment of patch selection by grazing cattle in semi-arid savannas.

The selection of different patch types for grazing by cattle in tropical savannas is well documented. Advances in high resolution satellite imagery and computing power now allow us to identify patch types over an entire paddock, combined with GPS collars as a non instrusive method of capturing positional data, an accurate and comprehensive picture of landscape use by cattle can be quantified.

Purification and physicochemical, kinetic and immunological properties of allosteric serine hydroxymethyltransferase from monkey liver.

The homogeneous serine hydroxymethyltransferase purified from monkey liver, by the use of Blue Sepharose affinity chromatography, exhibited positive homotropic co-operative interactions (h = 2.5) with tetrahydrofolate and heterotropic interactions with L-serine and nicotinamide nucleotides. The enzyme had an unusually high temperature optimum of 60 degrees C and was protected against thermal inactivation by L-serine. The allosteric effects were abolished when the monkey liver enzyme was purified by using a heat-denaturation step in the presence of L-serine, a procedure adopted by earlier workers for the purification of this enzyme from mammalian and bacterial sources. The enzyme activity was inhibited completely by N5-methyltetrahydrofolate, N5-formyltetrahydrofolate, dichloromethotrexate, aminopterin and D-cycloserine, whereas methotrexate and dihydrofolate were partial inhibitors. The insoluble monkey liver enzyme-antibody complex was catalytically active and failed to show positive homotropic co-operative interactions with tetrahydrofolate (h = 1) and heterotropic interactions with NAD+. The enzyme showed a higher heat-stability in a complex with its antibody than as the free enzyme. These results highlight the pitfalls in using a heat-denaturation step in the purification of allosteric enzymes.

The Interplay Between KSHV-encoded Viral Cyclin and CDK-inhibitors p27Kip1 and p21Cip1 -implications for Viral Lymphomagenesis

Cell division, which leads to the birth of two daughter cells, is essential for the growth and development of all organisms. The reproduction occurs in a series of events separated in time, designated as the cell cycle. The cell cycle progression is controlled by the activity of cyclin-dependent kinases (CDK). CDKs pair with cyclins to become catalytically active and phosphorylate a broad range of substrates required for cell cycle progression. In addition to cyclins, CDKs are regulated by inhibitory and activating phosphorylation events, binding to CDK-inhibitory proteins (CKI), and also by subcellular localization. The control of the CDK activity is crucial in preventing unscheduled progression of the cell cycle with mistakes having potentially hazardous consequences, such as uncontrolled proliferation of the cells, a hallmark of cancer. The mammalian cell cycle is a target of several DNA tumor viruses that can deregulate the host s cell cycle with their viral oncoproteins. A human herpesvirus called Kaposi s sarcoma herpesvirus (KSHV) is implicated in the cause of Kaposi s sarcoma (KS) and lymphoproliferative diseases such as primary effusion lymphomas (PEL). KSHV has pirated several cell cycle regulatory genes that it uses to manipulate its host cell and to induce proliferation. Among these gene products is a cellular cyclin D homologue, called viral cyclin (v-cyclin) that can activate cellular CDKs leading to the phosphorylation of multiple target proteins. Intriguingly, PELs that are naturally infected with KSHV consistently express high levels of CDK inhibitor protein p27Kip1 and still proliferate actively. The aim of this study was to investigate v-cyclin complexes and their activity in PELs, and search for an explanation why CKIs, such as p27Kip1 and p21Cip1 are unable to inhibit cell proliferation in this type of lymphoma. In this study, we found that v-cyclin binds to p27Kip1 in PELs, and confirmed this novel interaction also in the overexpression models. We observed that p27Kip1 associated with v-cyclin was also phosphorylated by a v-cyclin-associated kinase and identified cellular CDK6 as the major kinase partner of v-cyclin responsible for this phosphorylation. Analysis of the p27Kip1 residues targeted by v-cyclin-CDK6 revealed that serine 10 (S10) is the major phosphorylation site during the latent phase of the KSHV replication cycle. This phosphorylation led to the relocalization of p27Kip1 to the cytoplasm, where it is unable to inhibit nuclear cyclin-CDK complexes. In the lytic phase of the viral replication cycle, the preferred phosphorylation site on p27Kip1 by v-cyclin-CDK6 changed to threonine 187 (T187). T187 phosphorylation has been shown to lead to ubiquitin-mediated degradation of p27Kip1 and downregulation of p27Kip1 was also observed here. v-cyclin was detected also in complex with p21Cip1, both in overexpression models and in PELs. Phosphorylation of p21Cip1 on serine 130 (S130) site by v-cyclin-CDK6 functionally inactivated p21Cip1 and led to the circumvention of G1 arrest induced by p21Cip1. Moreover, p21Cip1 phosphorylated by v-cyclin-associated kinase showed reduced binding to CDK2, which provides a plausible explanation why p21Cip1 is unable to inhibit cell cycle progression upon v-cyclin expression. Our findings clarify the mechanisms on how v-cyclin evades the inhibition of cell cycle inhibitors and suggests an explanation to the uncontrolled proliferation of KSHV-infected cells.

Implementing music therapy on an adolescent inpatient unit: A mixed-methods evaluation of acceptability, experience of participation and perceived impact

Objective: We aimed to assess the feasibility of delivering a music therapy program on adolescent psychiatric wards. Method: We undertook a mixed-methods evaluation of a pilot program. Various active and receptive techniques were employed in group music therapy sessions delivered as part of a structured clinical program. Data collected in interviews with participants and staff and feedback questionnaires were thematically and descriptively analysed and triangulated. Results: Data from 62 questionnaires returned by 43 patients who took part in 16 music therapy sessions, and seven staff, evidenced strong support for music therapy. Patients typically reported experiencing sessions as relaxing, comforting, uplifting, and empowering; >90% would participate by choice and use music therapeutically in the future. Staff endorsed music therapy as valuable therapeutically, reporting that patients engaged enthusiastically and identified sessions as improving their own moods and ward milieu. Conclusions: Integration of music therapy in inpatient treatment of adolescents is feasible and acceptable, and is valued by staff and patients as a complement to ‘talking therapies’. Participation is enjoyed and associated with outcomes including improvement in mood, expression of feelings and social engagement consistent with recovery.

Inflammation and tissue destruction in arthritides and periodontal disease

The principal aim of this study was to examine diseases characterized by inflammatory injury, especially human arthritides and periodontitis, with specific interest to final effector enzymes of tissue destruction and address the possible future tools to prevent permanent tissue loss. We used biochemical and immunological methods applied to synovial tissue samples, samples of synovial fluid, and samples of peripheral blood. In Study IV, we used established clinical inflammatory injury indicator probing pocket depth and used it to derive a new clinical measure of systemic burden, periodontal inflammatory burden index. In study I, we showed a difference in the effector enzymes of peripheral blood leukocytes and leukocytes from inflamed synovial fluid of rheumatoid arthritis and reactive arthritis patients. The effector enzyme activities were higher in synovial fluid than in peripheral blood. In study II, we showed the presence of collagenase-3 in rheumatoid synovial tissue samples, relative resistance of the enzyme to inhibition in vitro and developed an electrophoretic method for detection of collagenase-3 in presence of collagenase-1. In study III, we carried out an open label study of doxycycline treatment of 12 RA patients. During the treatment period, we observed an improvement in several of the biochemical and psychosocial variables used to assess the status of the patients. In study IV, we showed a clearly lower level of periodontal inflammatory injury in chronic periodontitis patients referred for periodontal treatment. In this cross-sectional pilot study, we showed lower levels of inflammatory injury in periodontitis patients using statin than in those not receiving statin treatment. The difference was of same magnitude in patients using simvastatin or atorvastatin. The weighted index of inflammatory burden, PIBI, which emphasizes the burden imposed by the deepest pathological pockets on the system showed values consistent with a wider scale to ease future studies on the inflammatory burden associated with periodontitis.

Using genomic data to make indirect (and unauthorized) estimates of disease risk

The number of genetic factors associated with common human traits and disease is increasing rapidly, and the general public is utilizing affordable, direct-to-consumer genetic tests. The results of these tests are often in the public domain. A combination of factors has increased the potential for the indirect estimation of an individual's risk for a particular trait. Here we explain the basic principals underlying risk estimation which allowed us to test the ability to make an indirect risk estimation from genetic data by imputing Dr. James Watson's redacted apolipoprotein E gene (APOE) information. The principles underlying risk prediction from genetic data have been well known and applied for many decades, however, the recent increase in genomic knowledge, and advances in mathematical and statistical techniques and computational power, make it relatively easy to make an accurate but indirect estimation of risk. There is a current hazard for indirect risk estimation that is relevant not only to the subject but also to individuals related to the subject; this risk will likely increase as more detailed genomic data and better computational tools become available.