The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis

Multiple sclerosis (MS) is an autoimmune disease with a genetic component, caused at least in part by aberrant lymphocyte activity. The whole blood mRNA transcriptome was measured for 99 untreated MS patients: 43 primary progressive MS, 20 secondary progressive MS, 36 relapsing remitting MS and 45 age-matched healthy controls. The ANZgene Multiple Sclerosis Genetics Consortium genotyped more than 300 000 SNPs for 115 of these samples. Transcription from genes on translational regulation, oxidative phosphorylation, immune synapse and antigen presentation pathways was markedly increased in all forms of MS. Expression of genes tagging T cells was also upregulated (P < 10-12) in MS. A T cell gene signature predicts disease state with a concordance index of 0.79 with age and gender as co-variables, but the signature is not associated with clinical course or disability. The ANZgene genome wide association screen identified two novel regions with genome wide significance: one encoding the T cell co-stimulatory molecule, CD40; the other a region on chromosome 12q13-14. The CD40 haplotype associated with increased MS susceptibility has decreased gene expression in MS (P < 0.0007). The second MS susceptibility region includes 17 genes on 12q13-14 in tight linkage disequilibrium. Of these, only 13 are expressed in leukocytes, and of these the expression of one, FAM119B, is much lower in the susceptibility haplotype (P tdthomlt; 10-14). Overall, these data indicate dysregulation of T cells can be detected in the whole blood of untreated MS patients, and supports targeting of activated T cells in therapy for all forms of MS.

Breeding and fecundity of the endemic Australian gudgeon, sleepy cod Oxyeleotris lineolatus (Steindachner 1867) (Eleotridae)

Sleepy cod (Oxyeleotris lineolatus Steindachner) is a tropical species of eleotrid native to northern Australia. A related species, sand or marbled goby, is the highest priced freshwater fish in Asia, and a market for a similar fish exists in expatriate Chinese communities. Sleepy cod breed when minimum temperatures reach 24 °C for more than 3 days. During the breeding season the genital papilla is broad and flattened in females compared to the triangular papilla of males and juveniles. Spawning pairs were usually of approximately equal size. Females could spawn up to 10 times during one breeding season. Wet weather increased the frequency of spawning. Eggs were usually laid hanging from the underside of a surface. Most spawning occurred between 05:00 and 10:00 h. Females attended egg masses immediately after spawning, after which males cared for eggs until hatching, 3–5 days later. Agitation of the egg mass was essential for development. The mean number of eggs per spawning was 43 130. Larvae commenced feeding 2–5 days after hatching, on plankton from 100 to 250 m in size. A spawning trap used to collect egg masses is described. The breeding biology of sleepy cod is considered to be an adaptation to the monsoonal tropics.

Specimen-based databases of Australian plant pathogens: past, present and future

Specimen-based records of most of the plant pathogens that occur in Australia can be accessed through the Australian Plant Disease Database and the Australian Plant Pest Database. These databases and the herbaria that underpin them are important resources for resolving quarantine and trade issues as well as for the diagnosis of plant diseases. The importance of these collections and databases to Australia's agricultural industries is discussed.

Heritability of reproductive traits and genetic correlations with growth in the black tiger prawn Penaeus monodon reared in tanks

Captive-reared broodstock of the black tiger prawn (Penaeus monodon) have exhibited poor reproductive performance limiting attempts to domesticate this species. The potential for improved reproductive performance was assessed by determining heritabilities of four measures of reproductive performance, their genetic correlations with each other and with growth rate and weight at age. Heritability estimates (h2 ± S.E.) obtained from √ (days to spawn), √ (egg number), √ (nauplii number) and arcsin √ (proportion hatched) were 0.47 ± 0.15, 0.41 ± 0.18, 0.27 ± 0.16, and 0.18 ± 0.16, respectively. Estimates of genetic correlations between reproductive traits and weight at age, or growth rate were less than 0.5 except for √ (egg number) and weight at 54 weeks (0.93 ± 0.19) and √ (egg number) and 16-54-week growth (0.63 ± 0.29).

Comparative performance of Corymbia hybrids and parental species in subtropical Queensland and implications for breeding and deployment.

Eighty six full-sib Corymbia F1 hybrid families (crosses between C. torelliana and four spotted gum taxa: C. citriodora subsp. variegata, C. citriodora subsp. citriodora, C. henryi and C. maculata), were planted in six trials across six disparate sites in south-eastern Queensland to evaluate their productivity and determine their potential utility for plantation forestry. In each trial, the best-growing 20% of hybrid families grew significantly faster (P=0.05) than open-pollinated seedlots of the parent species Corymbia citriodora subsp. variegata, ranging from 107% to 181% and 127% to 287% of the height and diameter respectively. Relative performance of hybrid families growing on more than one site displayed consistency in ranking for growth across sites and analysis showed low genotype-by-environment interaction. Heritability estimates based on female and male parents across two sites at age six years for height and diameter at breast height, were high (0.62±0.28 to 0.64±0.35 and 0.31±0.21 to 0.69±0.37 respectively), and low to moderate (0.03±0.04 to 0.33±0.22) for stem straightness, branch size, incidence of ramicorns, and frost and disease resistance traits at ages one to three years. The proportion of dominance variance for height and diameter had reduced to zero by age six years. Based on these promising results, further breeding and pilot-scale family forestry and clonal forestry deployment is being undertaken. These results have also provided insights regarding the choice of a future hybrid breeding strategy.

Population genetic structure and genetic diversity of three critically endangered Pristis sawfishes in Australian waters.

Northern Australia is considered to be one of the last strongholds for three critically endangered sawfishes, Pristis zijsron, Pristis clavata, and Pristis microdon, making these populations of global significance. Population structure and levels of genetic diversity were assessed for each species across northern Australia using a portion of the mitochondrial control region. Statistically significant genetic structure was detected in all three species, although it was higher in P. microdon (F-ST = 0.811; N = 149) than in either P. clavata (F-ST = 0.419; N = 73) or P. zijsron (F-ST = 0.202; N = 49), possibly due to a much higher and/or localized level of female philopatry in P. microdon. The overall levels of haplotype diversity in P. zijsron (h = 0.555), P. clavata (h = 0.489), and P. microdon (h = 0.650) were moderate, although it appears to be reduced in the assemblages of P. zijsron and P. clavata in the Gulf of Carpentaria (h = 0.342 and h = 0.083, respectively). Since female migration (replenishment) between regions is unlikely, conservation plans should strive to maintain current levels of diversity and abundances in the regional assemblages of each species.

Tropical peach breeding and evaluation

Breeding new peach and nectarine cultivars that are adapted to tropical climates and produce fruit of high quality.

Noise sensitivity medical, psychological and genetic aspects

Noise can be defined as unwanted sound. It may adversely affect the health and well-being of individuals. Noise sensitivity is a personality trait covering attitudes towards noise in general and a predictor of noise annoyance. Noise sensitive individuals are more affected by noise than less sensitive individuals. The determinants and characteristics related to noise sensitivity are rather poorly known. The risk of health effects caused by noise can be hypothesized to be higher for noise sensitive individuals compared to those who are not noise sensitive. A cardiovascular disease may be an example of outcomes. The general aim of the present study was to investigate the association of noise sensitivity with specific somatic and psychological factors, including the genetic component of noise sensitivity, and the association of noise sensitivity with mortality. The study was based on the Finnish Twin Cohort of same-sex twin pairs born before 1958. In 1988 a questionnaire was sent to twin pairs discordant for hypertension. 1495 individuals (688 men, 807 women) aged 31 88 years replied, including 573 twin pairs. 218 of the subjects lived in the Helsinki Metropolitan Area. Self-reported noise sensitivity, lifetime noise exposure and hypertension were obtained from the questionnaire study in 1988 and other somatic and psychological factors from the questionnaire study in 1981 for the same individuals. In addition, noise map information (1988 1992) from the Helsinki Metropolitan Area and mortality follow-up 1989 2003 were used. To evaluate the stability and validity of noise sensitivity, a new questionnaire was sent in 2002 to a sample of the subjects who had replied to the 1988 questionnaire. Of all subjects who had answered the question on noise sensitivity, 38 % were noise sensitive. Noise sensitivity was independent of noise exposure levels indicated in noise maps. Subjects with high noise sensitivity reported more transportation noise exposure than subjects with low noise sensitivity. Noise sensitive subjects reported transportation noise exposure outside the environmental noise map areas almost twice as often as non-sensitive subjects. Noise sensitivity was associated with hypertension, emphysema, use of psychotropic drugs, smoking, stress and hostility, even when lifetime noise exposure was adjusted for. Monozygotic twin pairs were more similar with regards noise sensitivity than dizygotic twin pairs, and quantitative genetic modelling indicated significant familiality. The best fitting genetic model provided an estimate of heritability of 36 %. Follow-up of subjects in the case-control study showed that cardiovascular mortality was significantly increased among noise sensitive women, but not among men. For coronary heart mortality the interaction of noise sensitivity and lifetime noise exposure was statistically significant in women. In conclusion, noise sensitivity has both somatic and psychological components. It does aggregate in families and probably has a genetic component. Noise sensitivity may be a risk factor for cardiovascular mortality in women.

Macadamia Breeding and Conservation

DEEDI is tendering for this project because it considers that macadamia breeding is essential for long-term industry viability and that new productive cultivars will be the basis for the industry to withstand future competition from overseas and from other nut crops.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Integrating crop improvement technologies for rapid genetic advance

This project developed a novel approach to integrating enhanced gene mapping technologies with crop modelling to enhance the rate of improvement in sorghum yield.

Biology, Management and Genetic Stock Structure of Mangrove Jack, (Lutjanus argentimaculatus) in Australia.

This project has contributed to the ecologically sustainable management of mangrove jack in Australia by providing comprehensive information on its biology, habitat requirements, population parameters and stock structure. Specifically, the project has resulted in an enhanced understanding of the life history of Australian mangrove jack, the levels of exploitation in its local fishery and the likely existence of a single genetic stock throughout Queensland.

Amyloid diseases at old age : a pathological, epidemiological, and genetic study

Along with the increased life span of individuals, the burden of old age-associated diseases has inevitably increased. Alzheimer s disease (AD), probably the most well known geriatric disease, belongs to the old age-associated amyloid diseases. The purpose of this study was to investigate the frequency, genetic and health-associated risk factors, mutual association, and amyloid proteins in two old age-associated amyloid disorders senile systemic amyloidosis (SSA) and cerebral amyloid angiopathy (CAA) as part of the prospective population-based Vantaa 85+ autopsy study on a Finnish population aged 85 years or more (Studies I-III), completed with a case report on a patient with advanced AGel amyloidosis (Study IV). The numbers of patients investigated in the studies (I-III) were 256, 74, and 63, respectively. The diagnosis and grading of amyloid were based upon histological examination of tissue samples obtained post mortem and stained with Congo red. The amyloid fibril and associated proteins were characterized by immunohistochemical staining methods. The genotype frequencies of 20 polymorphisms in 9 genes and information on health-associated risk factors in subjects with and without SSA and CAA were compared. In a Finnish population ≥ 95 years of age, SSA and CAA occurred in 36% and 49% of the subjects, respectively. In total, two-thirds of these very elderly individuals had SSA, CAA, or both. However, in only 14% of the population these two conditions co-occurred. In subjects 85 years or older, the prevalence of SSA was 25%. In this population, SSA was associated with age at the time of death (p=0.002), myocardial infarctions (MIs; p=0.004), the G/G (Val/Val) genotype of the exon 24 polymorphism in the alpha2-macroglobulin (α2M) gene (p=0.042) and with the H2 haplotype of the tau gene (p=0.016). In contrast, the presence of CAA was strongly associated with APOE e4 (p=0.0003), with histopathological AD (p=0.0005), and with clinical dementia (p=0.01) in both e4+ (p=0.02) and e4- (p=0.06) individuals. Apart from demonstrating the amyloid fibril proteins, complement proteins 3d (C3d) and 9 (C9) were detected in the amyloid deposits of CAA and AGel amyloidosis, and α2M protein was found in fibrous scar tissue close to SSA. In conclusion, this first population based study on SSA shows that both SSA and CAA are common in very elderly individuals. Old age, MIs, the exon 24 polymorphism of the α2M gene, and H1/H2 polymorphism of the tau gene associate with SSA while clinical dementia and APOE ε4 genotype associate with CAA. The high prevalence of CAA, combined with its association with clinical dementia independent of APOE genotype, neuropathological AD, or SSA, also highlights its clinical significance in the very aged, among which the serious end stage complications of CAA, namely multiple infarctions and hemorrhages, are rare. The report on a patient having advanced AGel amyloidosis added knowledge on the disease and showed that this generally benign condition occasionally may lead to death. Further studies are warranted to confirm the findings in other populations. Also, the role of α2M and tau in the pathogenesis of SSA and the involvement of complement in the process of amyloid beta (Aβ) protein elimination from the brain remain to be clarified. Finally, the high prevalence of SSA in the elderly raises the need for prospective clinical studies to define its clinical significance.