Molecular interactions involved in the transactivation of the human T-cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4).

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N- and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation.

Apparent versus true gene expression changes of three hypoxia-related genes in autopsy derived tissue and the importance of normalisation.

The aim of our work was to show how a chosen normal-isation strategy can affect the outcome of quantitative gene expression studies. As an example, we analysed the expression of three genes known to be upregulated under hypoxic conditions: HIF1A, VEGF and SLC2A1 (GLUT1). Raw RT-qPCR data were normalised using two different strategies: a straightforward normalisation against a single reference gene, GAPDH, using the 2(-ΔΔCt) algorithm and a more complex normalisation against a normalisation factor calculated from the quantitative raw data from four previously validated reference genes. We found that the two different normalisation strategies revealed contradicting results: normalising against a validated set of reference genes revealed an upregulation of the three genes of interest in three post-mortem tissue samples (cardiac muscle, skeletal muscle and brain) under hypoxic conditions. Interestingly, we found a statistically significant difference in the relative transcript abundance of VEGF in cardiac muscle between donors who died of asphyxia versus donors who died from cardiac death. Normalisation against GAPDH alone revealed no upregulation but, in some instances, a downregulation of the genes of interest. To further analyse this discrepancy, the stability of all reference genes used were reassessed and the very low expression stability of GAPDH was found to originate from the co-regulation of this gene under hypoxic conditions. We concluded that GAPDH is not a suitable reference gene for the quantitative analysis of gene expression in hypoxia and that validation of reference genes is a crucial step for generating biologically meaningful data.

A Framework for Building Hypercubes Using MapReduce

The European Space Agency's Gaia mission will create the largest and most precise three dimensional chart of our galaxy (the Milky Way), by providing unprecedented position, parallax, proper motion, and radial velocity measurements for about one billion stars. The resulting catalogue will be made available to the scientific community and will be analyzed in many different ways, including the production of a variety of statistics. The latter will often entail the generation of multidimensional histograms and hypercubes as part of the precomputed statistics for each data release, or for scientific analysis involving either the final data products or the raw data coming from the satellite instruments. In this paper we present and analyze a generic framework that allows the hypercube generation to be easily done within a MapReduce infrastructure, providing all the advantages of the new Big Data analysis paradigmbut without dealing with any specific interface to the lower level distributed system implementation (Hadoop). Furthermore, we show how executing the framework for different data storage model configurations (i.e. row or column oriented) and compression techniques can considerably improve the response time of this type of workload for the currently available simulated data of the mission. In addition, we put forward the advantages and shortcomings of the deployment of the framework on a public cloud provider, benchmark against other popular solutions available (that are not always the best for such ad-hoc applications), and describe some user experiences with the framework, which was employed for a number of dedicated astronomical data analysis techniques workshops.

A Framework for Building Hypercubes Using MapReduce

The European Space Agency's Gaia mission will create the largest and most precise three dimensional chart of our galaxy (the Milky Way), by providing unprecedented position, parallax, proper motion, and radial velocity measurements for about one billion stars. The resulting catalogue will be made available to the scientific community and will be analyzed in many different ways, including the production of a variety of statistics. The latter will often entail the generation of multidimensional histograms and hypercubes as part of the precomputed statistics for each data release, or for scientific analysis involving either the final data products or the raw data coming from the satellite instruments. In this paper we present and analyze a generic framework that allows the hypercube generation to be easily done within a MapReduce infrastructure, providing all the advantages of the new Big Data analysis paradigmbut without dealing with any specific interface to the lower level distributed system implementation (Hadoop). Furthermore, we show how executing the framework for different data storage model configurations (i.e. row or column oriented) and compression techniques can considerably improve the response time of this type of workload for the currently available simulated data of the mission. In addition, we put forward the advantages and shortcomings of the deployment of the framework on a public cloud provider, benchmark against other popular solutions available (that are not always the best for such ad-hoc applications), and describe some user experiences with the framework, which was employed for a number of dedicated astronomical data analysis techniques workshops.

Mating type, mefenoxam sensitivity, and pathotype diversity in Phytophthora infestans isolates from tomato in Brazil

The objective of this work was to characterize 79 Phytophthora infestans isolates collected in tomato (Solanum lycopersicum) fields, as to mating type, mefenoxam sensitivity, and pathotype composition. The isolates were sampled in 2006 and 2007 in seven Brazilian states as well as in the Distrito Federal. They were characterised as to mating type (n=79), sensitivity to fungicide mefenoxam (n=79), and virulence to three major resistance genes Ph-1, Ph-2, and Ph-3/Ph-4 (n=62). All isolates were of the mating type A1. Resistant isolates were detected in all sampled states, and its average frequency was superior to 50%. No difference was detected in pathotype diversity, neither between subpopulations collected in 2006 and 2007 nor between isolates grouped as resistant or intermediately sensitive to mefenoxam. All major resistance genes were overcome at different frequencies: Ph-1, 88.7%; Ph-2, 64.5%; and Ph-3/Ph-4, 25.8%. Isolates with virulence genes able to overcome all major resistance genes were detected at low frequencies. Tomato breeding programs in Brazil must avoid the development of cultivars with resistance based exclusively on major genes.

Relation between plaque type, plaque thickness, blood shear stress, and plaque stress in coronary arteries assessed by X-ray Angiography and Intravascular Ultrasound

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries. Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound(IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations. Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall. Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed.

Women in leadership: Three essays

GENDER EMPOWERMENT: EFFECTS OF GODS, GEOGRAPHY, AND GDP¦Fenley, M., & Antonakis, J.¦ABSTRACT¦We examined the determinants of women's empowerment in the economy and political leadership in 178 countries. Given the androcentric nature of most religions, we hypothesized that high degrees of country-level theistic belief create social conditions that impede the progression of women to power. The dependent variable was the Gender Empowerment index of the United Nations Development Program, which captures the participation of women in political leadership, management, and their share of national income. Controlling for GDP per capita as well as the fixed-effects of the dominant type of religion and legal origin and instrumenting all endogenous variables with geographic or historical variables, our results show that atheism has a significant positive effect on gender empowerment. These results are driven by the rule of law, which in addition to being a catalyst for economic development, appears to crowd-out the informal regulation of behavior due to religious norms.¦DEVELOPING WOMEN LEADERS: COMPARING A TRANSFORMATIONAL AND A CHARISMATIC LEADERSHIP INTERVENTION¦Fenley, M., Jacquart, P., & Antonakis, J.¦ABSTRACT¦Along with a gender imbalance in leadership role occupancy, most leadership interventions have been conducted with samples of men. We conducted an experiment wherein we assigned female participants (n = 38, mean age = 35 years) to one of two conditions: Transformational (i.e., "standard") leadership training or charismatic leadership training. The two interventions were essentially equivalent, except that we also focused on developing the "charismatic leadership tactics" (e.g., rhetorical skills) of participants in the charismatic condition. After the interventions, we randomly assigned participants into problem-solving teams that required extensive interaction. Each team had an equal number of participants having received transformational training or charismatic training. At the end of the team exercises, participants rated each of their team members on a leadership prototypicality measure. Results indicated that those who received charismatic training scored higher (a) on prototypicality (standardized  = .42) and (b) on a test of declarative knowledge of charismatic rhetorical strategies (i.e., a manipulation check, standardized  = .76). Furthermore, the score on the test fully mediated the effect of the treatment on prototypicality (standardized indirect  = .32). We discuss the importance and practical implications of these results.¦CHANGING ATTITUDES TOWARDS WOMEN IN A MALE SEX-TYPE WORK ENVIRONMENT: EVIDENCE FROM A FIELD EXPERIMENT IN EUROPEAN ATHLETICS¦Fenley, M.¦ABSTRACT¦Most sports organizations have a similar gender gap in leadership as do the majority of non-sport organizations. Women's careers sputter somewhere at coaching level positions and few women obtain top leadership positions. Greater awareness of gender inequalities in general, and in leadership in particular, could decrease gender discrimination and increase women's presence at upper levels. The goal of this study was to evaluate the impact of an intervention using an online gender awareness exercise. Participants (n = 1,001 participants, n = 32 countries) were randomly assigned to one of eight conditions in a 2 (a discriminating perspective-taking story or a non-discriminating perspective-taking story) by 2 (gender quiz or no gender quiz) by 2 (diversity quiz or no diversity quiz) factorial design. The results show that the online perspective taking exercise changed initial sexist attitudes. Participants having taken a diversity quiz had less sexist attitudes (as measured by the Modern- and Old-fashioned sexism scale) than did participants who did not take the diversity quiz (irrespective of perspective-taking story). The combination of having taken a diversity quiz with a gender quiz had the biggest impact on attitudes for the non-discriminating story.

JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases (n = 29), as well as three matched controls per case (n = 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4(+) T-cell count, and decline. Survivors (n = 18) were defined as being alive for >1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls (P = 0.08), which was highly significant for laboratory- and histologically confirmed PML cases (P = 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells (P = 0.04) and immunoglobulin G (IgG) responses (P = 0.005). IgG responses in survivors were positively correlated with CD4(+) T-cell counts (P = 0.049) and negatively with human immunodeficiency virus RNA loads (P = 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4(+) T-cell-matched controls and failed to mount JCV-specific antibody responses. JCV-specific T-cell and IgG responses may serve as prognostic markers for patients at risk.

Hybrid turbo FEC/ARQ systems and distributed space-time coding for cooperative transmission

Cooperative transmission can be seen as a "virtual" MIMO system, where themultiple transmit antennas are in fact implemented distributed by the antennas both at the source and the relay terminal. Depending on the system design, diversity/multiplexing gainsare achievable. This design involves the definition of the type of retransmission (incrementalredundancy, repetition coding), the design of the distributed space-time codes, the errorcorrecting scheme, the operation of the relay (decode&forward or amplify&forward) and thenumber of antennas at each terminal. Proposed schemes are evaluated in different conditionsin combination with forward error correcting codes (FEC), both for linear and near-optimum(sphere decoder) receivers, for its possible implementation in downlink high speed packetservices of cellular networks. Results show the benefits of coded cooperation over directtransmission in terms of increased throughput. It is shown that multiplexing gains areobserved even if the mobile station features a single antenna, provided that cell wide reuse of the relay radio resource is possible.

Complete DNA sequence of Kuraishia capsulata illustrates novel genomic features among budding yeasts (Saccharomycotina)

The numerous yeast genome sequences presently available provide a rich source of information for functional as well as evolutionary genomics but unequally cover the large phylogenetic diversity of extant yeasts. We present here the complete sequence of the nuclear genome of the haploid-type strain of Kuraishia capsulata (CBS1993(T)), a nitrate-assimilating Saccharomycetales of uncertain taxonomy, isolated from tunnels of insect larvae underneath coniferous barks and characterized by its copious production of extracellular polysaccharides. The sequence is composed of seven scaffolds, one per chromosome, totaling 11.4 Mb and containing 6,029 protein-coding genes, ~13.5% of which being interrupted by introns. This GC-rich yeast genome (45.7%) appears phylogenetically related with the few other nitrate-assimilating yeasts sequenced so far, Ogataea polymorpha, O. parapolymorpha, and Dekkera bruxellensis, with which it shares a very reduced number of tRNA genes, a novel tRNA sparing strategy, and a common nitrate assimilation cluster, three specific features to this group of yeasts. Centromeres were recognized in GC-poor troughs of each scaffold. The strain bears MAT alpha genes at a single MAT locus and presents a significant degree of conservation with Saccharomyces cerevisiae genes, suggesting that it can perform sexual cycles in nature, although genes involved in meiosis were not all recognized. The complete absence of conservation of synteny between K. capsulata and any other yeast genome described so far, including the three other nitrate-assimilating species, validates the interest of this species for long-range evolutionary genomic studies among Saccharomycotina yeasts.

Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.

While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN) are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG]) or the glial (endoneurium) compartments of the peripheral nerve. We used Ins2(Akita/+) mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM). Weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Ins2(Akita/+) and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2(Akita/+) mice and sex-matched littermate controls. Our phenotypic analysis of Ins2(Akita/+) mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM.

Data-parallel computation in parallel and distributed environments

The past few decades have seen a considerable increase in the number of parallel and distributed systems. With the development of more complex applications, the need for more powerful systems has emerged and various parallel and distributed environments have been designed and implemented. Each of the environments, including hardware and software, has unique strengths and weaknesses. There is no single parallel environment that can be identified as the best environment for all applications with respect to hardware and software properties. The main goal of this thesis is to provide a novel way of performing data-parallel computation in parallel and distributed environments by utilizing the best characteristics of difference aspects of parallel computing. For the purpose of this thesis, three aspects of parallel computing were identified and studied. First, three parallel environments (shared memory, distributed memory, and a network of workstations) are evaluated to quantify theirsuitability for different parallel applications. Due to the parallel and distributed nature of the environments, networks connecting the processors in these environments were investigated with respect to their performance characteristics. Second, scheduling algorithms are studied in order to make them more efficient and effective. A concept of application-specific information scheduling is introduced. The application- specific information is data about the workload extractedfrom an application, which is provided to a scheduling algorithm. Three scheduling algorithms are enhanced to utilize the application-specific information to further refine their scheduling properties. A more accurate description of the workload is especially important in cases where the workunits are heterogeneous and the parallel environment is heterogeneous and/or non-dedicated. The results obtained show that the additional information regarding the workload has a positive impact on the performance of applications. Third, a programming paradigm for networks of symmetric multiprocessor (SMP) workstations is introduced. The MPIT programming paradigm incorporates the Message Passing Interface (MPI) with threads to provide a methodology to write parallel applications that efficiently utilize the available resources and minimize the overhead. The MPIT allows for communication and computation to overlap by deploying a dedicated thread for communication. Furthermore, the programming paradigm implements an application-specific scheduling algorithm. The scheduling algorithm is executed by the communication thread. Thus, the scheduling does not affect the execution of the parallel application. Performance results achieved from the MPIT show that considerable improvements over conventional MPI applications are achieved.

Value Processingin Organizations - Individual Perceptions in Three Case Companies

Values and value processes are said to be needed in every organization nowadays, as the world is changing and companies have to have something to "keep it together". Organizational values, which are approvedand used by the personnel, could be the key. Every organization has values. But what is the real value of values? The greatest and most crucial challenge is the feasibility of the value process. The main point in this thesis is tostudy how organizational members at different hierarchical levels perceive values and value processes in their organizations. This includes themes such as how values are disseminated, the targets of value processing, factors that affect the process, problems that occur during the value implementation and improvements that could be made when organizational values are implemented. These subjects are studied from the perspective of organizational members (both managers and employees); individuals in the organizations. The aim is to get the insider-perspective on value processing, from multiple hierarchical levels. In this research I study three different organizations (forest industry, bank and retail cooperative) and their value processes. The data is gathered from companies interviewing personnel in the head office and at the local level. The individuals areseen as members of organizations, and the cultural aspect is topical throughout the whole study. Values and cultures are seen as the 'actuality of reality' of organizations, interpreted by organizational members. The three case companies were chosen because they represented different lines of business and they all implemented value processing differently. Sincethe emphasis in this study is at the local level, the similar size of the local units was also an important factor. Values are in 'fashion' -but what does the fashion tell us about the real corporate practices? In annual reports companies emphasize the importance and power of official values. But what is the real 'point' of values? Values are publicly respected and advertised, but still it seems that the words do not meet the deeds. There is a clear conflict between theoretical, official and substantive organizational values: in the value processing from words to real action. This contradiction in value processing is studied through individual perceptions in this study. I study the kinds of perceptions organizationalmembers have when values are processed from the head office to the local level: the official value process is studied from the individual's perspective. Value management has been studied more during the 1990's. The emphasis has usually been on managers: how they consider the values in organizations and what effects it has on the management. Recent literature has emphasized values as tools for improving company performance. The value implementation as a process has been studied through 'good' and 'bad' examples, as if one successful value process could be copied to all organizations. Each company is different with different cultures and personnel, so no all-powerful way of processing values exists. In this study, the organizational members' perceptions at different hierarchical levels are emphasized. Still, managers are also interviewed; this is done since managerial roles in value dissemination are crucial. Organizational values cannot be well disseminated without management; this has been proved in several earlier studies (e.g. Kunda 1992, Martin 1992, Parker 2000). Recent literature has not sufficiently emphasized the individual's (organizational member's) role in value processing. Organizations consist of differentindividuals with personal values, at all hierarchical levels. The aim in this study is to let the individual take the floor. Very often the value process is described starting from the value definition and ending at dissemination, and the real results are left without attention. I wish to contribute to this area. Values are published officially in annual reports etc. as a 'goal' just like profits. Still, the results/implementationof value processing is rarely followed, at least in official reports. This is a very interesting point: why do companies espouse values, if there is no real control or feedback after the processing? In this study, the personnel in three different companies is asked to give an answer. In the empirical findings, there are several results which bring new aspects to the research area of organizational values. The targets of value processing, factors effecting value processing, the management's roles and the problems in value implementation are presented through the individual's perspective. The individual's perceptions in value processing are a recurring theme throughout the whole study. A comparison between the three companies with diverse value processes makes the research complete

Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus).

Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies.

Genes outside The Hla Region affecting Susceptibility to Type 1 Diabetes - The Role of Iddm2 and Iddm9 in the Finnish Population

Tyypin 1 diabeteksen perinnöllinen alttius Suomessa - HLA-alueen ulkopuolisten alttiuslokusten IDDM2 ja IDDM9 rooli taudin periytymisessä HLA-alue, joka sijaitsee kromosomissa 6p21.3, vastaa noin puolesta perinnöllisestä alttiudesta sairastua tyypin 1 diabetekseen. Myös HLA-alueen ulkopuolisten lokusten on todettu liittyvän sairausalttiuteen. Näistä kolmen lokuksen on varmistettu olevan todellisia alttiuslokuksia ja lisäksi useiden muiden, vielä varmistamattomien lokusten, on todettu liittyvän sairausalttiuteen. Tässä tutkimuksessa 12:n HLA-alueen ulkopuolisen alttiuslokuksen kytkentä tyypin 1 diabetekseen tutkittiin käyttäen 107:aa suomalaista multiplex-perhettä. Jatkotutkimuksessa analysoitiin IDDM9-alueen kytkentä ja assosiaatio sairauteen laajennetuissa perhemateriaaleissa sekä IDDM2-alueen mahdollinen interaktio HLA-alueen kanssa sairauden muodostumisessa. Lisäksi suoritettiin IDDM2-alueen suojaavien haplotyyppien alatyypitys tarkoituksena tutkia eri haplotyyppien käyttökelpoisuutta sairastumisriskin tarkempaa ennustamista varten. Ensimmäisessä kytkentätutkimuksessa ei löytynyt koko genomin tasolla merkitsevää tai viitteellistä kytkentää tutkituista HLA-alueen ulkopuolisista lokuksista. Voimakkain havaittu nimellisen merkitsevyyden tavoittava kytkentä nähtiin IDDM9-alueen markkerilla D3S3576 (MLS=1.05). Tutkimuksessa ei kyetty varmistamaan tai sulkemaan pois aiempia kytkentähavaintoja tutkituilla lokuksilla, mutta IDDM9-alueen jatkotutkimuksessa havaittu voimakas kytkentä (MLS=3.4) ja merkitsevä assosiaatio (TDT p=0.0002) viittaa vahvasti siihen, että 3q21-alueella sijaitsee todellinen tyypin 1 diabeteksen alttiusgeeni, jolloin alueen kattava assosiaatiotutkimus olisi perusteltu jatkotoimenpide. Sairauteen altistava IDDM2-alueen MspI-2221 genotyyppi CC oli nimellisesti yleisempi matalan tai kohtalaisen HLA-sairastumisriskin diabeetikoilla, verrattuna korkean HLA-riskin potilaisiin (p=0.05). Myös genotyyppijakauman vertailu osoitti merkitsevää eroa ryhmien välillä (p=0.01). VNTR-haplotyyppitutkimus osoitti, että IIIA/IIIA-homotsygootin sairaudelta suojaava vaikutus on merkitsevästi voimakkaampi kuin muiden luokka III:n genotyypeillä. Nämä tulokset viittaavat IDDM2-HLA -vuorovaikutukseen sekä siihen että IDDM2-alueen haplotyyppien välillä esiintyy etiologista heterogeniaa. Tämän johdosta IDDM2-alueen haplotyyppien tarkempi määrittäminen voisi tehostaa tyypin 1 diabeteksen riskiarviointia.