Cognitive functioning in older twins: The Older Australian Twins Study

Aim: To examine the concordance rates of common medical conditions and neurocognitive performance in monozygotic (MZ) and dizygotic (DZ) older twins. Methods: Twins aged ≥65 years and living in the three Eastern states of Australia were recruited through the Australian Twin Registry and underwent detailed neuropsychological and medical assessment. Results: Assessments were conducted on 113 MZ and 96 DZ twin pairs, with a mean age of 70.5 years. MZ twins were more concordant than DZ twins for hypertension and asthma. MZ twins had higher correlations than DZ twins on most neuropsychological tests, with the exception of some tests related to processing speed. The concordance rate for mild cognitive impairment or dementia was 76.2% in MZ twins and 42.9% in DZ twins, a non-significant difference. Conclusions: Except for some aspects of processing speed, most cognitive functions in older individuals show significant heritability. The heritability of neurocognitive disorders is, however, low.

Investigating brain connectivity heritability in a twin study using diffusion imaging data

Heritability of brain anatomical connectivity has been studied with diffusion-weighted imaging (DWI) mainly by modeling each voxel's diffusion pattern as a tensor (e.g., to compute fractional anisotropy), but this method cannot accurately represent the many crossing connections present in the brain. We hypothesized that different brain networks (i.e., their component fibers) might have different heritability and we investigated brain connectivity using High Angular Resolution Diffusion Imaging (HARDI) in a cohort of twins comprising 328 subjects that included 70 pairs of monozygotic and 91 pairs of dizygotic twins. Water diffusion was modeled in each voxel with a Fiber Orientation Distribution (FOD) function to study heritability for multiple fiber orientations in each voxel. Precision was estimated in a test-retest experiment on a sub-cohort of 39 subjects. This was taken into account when computing heritability of FOD peaks using an ACE model on the monozygotic and dizygotic twins. Our results confirmed the overall heritability of the major white matter tracts but also identified differences in heritability between connectivity networks. Inter-hemispheric connections tended to be more heritable than intra-hemispheric and cortico-spinal connections. The highly heritable tracts were found to connect particular cortical regions, such as medial frontal cortices, postcentral, paracentral gyri, and the right hippocampus.

A taxonomic assessment of the Australian Dusky Antechinus Complex: A new species, the Tasman Peninsula Dusky Antechinus (Antechinus vandycki sp. nov.) and an elevation to species of the Mainland Dusky Antechinus (Antechinus swainsonii mimetes (Thomas))

In 2014, the northern outlying population of carnivorous marsupial Dusky Antechinus (Antechinus swainsonii) was nominated a new species, A. arktos. Here, we describe a further new species in the dasyurid A. swainsonii complex, which now contains five taxa. We recognise two distinct species from Tasmania, formerly represented by A. swainsonii swainsonii (Waterhouse); one species (and 2 subspecies) from mainland south-eastern Australia, formerly known as A. swainsonii mimetes (Thomas) and A. swainsonii insulanus Davison; and one species from the Tweed Caldera in mid-eastern Australia, formerly known as A. s. mimetes but recently described as A. arktos Baker, Mutton, Hines and Van Dyck. Primacy of discovery dictates the Tasmanian Dusky Antechinus A. swainsonii (Waterhouse) is nominate; the Mainland Dusky Antechinus taxa, one raised from subspecies within A. swainsonii mimetes (Thomas) is elevated to species (now A. mimetes mimetes) and the other, A. swainsonii insulanus Davison is transferred as a subspecies of A. mimetes (now A. mimetes insulanus); a species from Tasmania, the Tasman Peninsula Dusky Antechinus, is named A. vandycki sp. nov. These taxa are strongly differentiated: geographically (in allopatry), morphologically (in coat colour and craniodental features) and genetically (in mtDNA, 7.5-12.5% between species pairs).

Identification of a putative cellulase gene in the giant freshwater prawn, Macrobrachium rosenbergii (De Man, 1879)

Nutrition plays an important role in the development of all organisms and in particular that of farmed aquatic species where costs associated with feed can often exceed 60% of total production costs. Crustacean species in addition, have the added metabolic requirement for regular moulting to allow normal growth and this requires large amounts of energy in the form of sugars (glucose). The current study explored the capacity of the giant freshwater prawn to produce endogenous cellulose-degrading enzymes capable of extracting nutrients (simple sugars) from plant sources in formulated feeds used in the prawn aquaculture industry. We identified a putative cellulase cDNA fragment in the target organism of 1576 base pairs in length of non-microbial origin that after protein modelling exhibited a TM-score of 0.916 with a described cellulase reported from another crustacean species. The functional role of cellulase enzymes is to hydrolyse cellulose to glucose and the fragment identified in GFP was highly expressed in the hepatopancreas, the site of primary food digestion and absorption in crustaceans. Hepatopancreatic tissue from Macrobrachium rosenbergii also showed active digestion of cellulose to glucose following an endoglucanase assay. Cellulase gene(s) are present in the genomes of many invertebrate taxa and play an active role in the conversion of cellulose to available energy. Identification and characterization of endogenous cellulase gene(s) in giant freshwater prawn can assist development of the culture industry because the findings confirm that potentially greater levels of low-cost plant-material could be included in artificial formulated diets in the future without necessarily compromising individual growth performance. Ultimately, this development may contribute to more efficient, cost-effective production systems for freshwater prawn culture stocks that meet the animal's basic nutritional requirements and that also support good individual growth rates.

Academic potential and cognitive functioning of long-term survivors after childhood liver transplantation

This cross-sectional study assessed intellect, cognition, academic function, behaviour, and emotional health of long-term survivors after childhood liver transplantation. Eligible children were >5 yr post-transplant, still attending school, and resident in Queensland. Hearing and neurocognitive testing were performed on 13 transplanted children and six siblings including two twin pairs where one was transplanted and the other not. Median age at testing was 13.08 (range 6.52-16.99) yr; time elapsed after transplant 10.89 (range 5.16-16.37) yr; and age at transplant 1.15 (range 0.38-10.00) yr. Mean full-scale IQ was 97 (81-117) for transplanted children and 105 (87-130) for siblings. No difficulties were identified in intellect, cognition, academic function, and memory and learning in transplanted children or their siblings, although both groups had reduced mathematical ability compared with normal. Transplanted patients had difficulties in executive functioning, particularly in self-regulation, planning and organization, problem-solving, and visual scanning. Thirty-one percent (4/13) of transplanted patients, and no siblings, scored in the clinical range for ADHD. Emotional difficulties were noted in transplanted patients but were not different from their siblings. Long-term liver transplant survivors exhibit difficulties in executive function and are more likely to have ADHD despite relatively intact intellect and cognition.

Characterization of novel microsatellite markers derived from Korean rose bitterling (Rhodeus uyekii) genomic library

Korean rose bitterling (Rhodeus uyekii) is a freshwater fish endemic to Korea. Natural populations of this species have experienced severe declines as a result of habitat fragmentation and water pollution. To conserve and restore R. uyekii, the genetic diversity of this species needs to be assessed at the population level. Eighteen novel polymorphic microsatellite loci for R. uyekii were developed using an enriched partial genomic library. Polymorphisms at these loci were studied in 150 individuals collected from three populations. The number of alleles at each locus ranged from 3 to 47 (mean = 17.1). Within the populations, the observed heterozygosity ranged from 0.032 to 1.000, expected heterozygosity from 0.082 to 0.967, and polymorphism information content from 0.078 to 0.950. Six loci showed significant deviation from Hardy-Weinberg equilibrium after Bonferroni’s correction, and no significant linkage disequilibrium was detected between most locus pairs, except in three cases. These highly informative microsatellite markers should be useful for genetic population structure analyses of R. uyekii.

Whole-genome screening in ankylosing spondylitis: Evidence of non-MHC genetic-susceptibility loci

Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonparametric linkage analysis was performed. Regions were identified showing "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q, 10q, 16q, and 19q. The MHC locus was identified as encoding the greatest component of susceptibility, with an overall LOD score of 15.6. The strongest non-MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results strongly support the presence of non-MHC genetic-susceptibility factors in AS and point to their likely locations.

Ankylosing spondylitis in West Africans - evidence for a non-HLA-B27 protective effect

Objective - To determine the prevalence of ankylosing spondylitis in the Fula ethnic group in The Gambia, and relate the disease prevalence to the B27 frequency and subtype distribution of that population. Methods - 215 first degree relatives of 48 B27 positive Fula twin pairs, and 900 adult Fula males were screened for ankylosing spondylitis by clinical and, where appropriate, radiographic means. The B27 prevalence was determined by PCR/sequence specific oligonucleotides on finger prick samples from 100 unrelated Fula, and B27 subtype distribution by SSCP on unrelated B27 positive individuals. This data were then compared with the prevalence of ankylosing spondylitis among B27 positive Caucasians. Results - No case of ankylosing spondylitis was seen. Six per cent of Fula are B27 positive, of which 32% are B*2703 and 68% B*2705. Assuming the penetrance of ankylosing spondylitis in B27 positive Fula is the same as in B27 positive Caucasians, the probability of not observing any cases of ankylosing spondylitis among the Fula examined is remote (P = 6.7 x 10-6). Similarly, the chance of not seeing any cases among those expected to be either B*2705 or B*2703 was small (P = 3.2 x 10-4 for B*2705, and P = 0.02 for B*2703). Conclusions - The risk of developing ankylosing spondylitis in B27 positive Fula is lower than in B27 positive Caucasians. This is not explained by the B27 subtype distribution among Fula, and suggests the presence of some non-B27 protective factor reducing the prevalence of ankylosing spondylitis in this population.

Replication of association of IL1 gene complex members with ankylosing spondylitis in Taiwanese Chinese

Objective: To test the association of interleukin 1 (IL1) gene family members with ankylosing spondylitis (AS), previously reported in Europid subjects, in an ethnically remote population. Methods: 200 Taiwanese Chinese AS patients and 200 ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (SNPs) and the IL1RN.VNTR, markers previously associated with AS. Allele, genotype, and haplotype frequencies were compared between cases and controls. Results: Association of alleles and genotypes of the markers IL1F10.3, IL1RN.4, and IL1RN.VNTR was observed with AS (p<0.05). Haplotypes of pairs of these markers and of the markers IL1RN.6/1 and IL1RN.6/2 were also significantly associated with AS. The strongest associations observed were with the marker IL1RN.4, and with the two-marker haplotype IL1RN.4-IL1RN.VNTR (both p = 0.004). Strong linkage disequilibrium was observed between all marker pairs except those involving IL1B-511 (D′ 0.4 to 0.9, p<0.01). Conclusions: The IL1 gene cluster is associated with AS in Taiwanese Chinese. This finding provides strong statistical support that the previously observed association of this gene cluster with AS is a true positive finding.

Susceptibility to ankylosing spondylitis in twins: The role of genes, HLA, and the environment

Objective To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS). Methods Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence- specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS. Results Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co- twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance. Conclusion Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.

A genome-wide screen for susceptibility loci in ankylosing spondylitis

Objective. To localize the regions containing genes that determine susceptibility to ankylosing spondylitis (AS). Methods. One hundred five white British families with 121 affected sibling pairs with AS were recruited, largely from the Royal National Hospital for Rheumatic Diseases AS database. A genome-wide linkage screen was undertaken using 254 highly polymorphic microsatellite markers from the Medical Research Council (UK) (MRC) set. The major histocompatibility complex (MHC) region was studied more intensively using 5 microsatellites lying within the HLA class III region and HLA-DRB1 typing. The Analyze package was used for 2-point analysis, and GeneHunter for multipoint analysis. Results. When only the MRC set was considered, 11 markers in 7 regions achieved a P value of ≤0.01. The maximum logarithm of odds score obtained was 3.8 (P = 1.4 x 10-5) using marker D6S273, which lies in the HLA class III region. A further marker used in mapping of the MHC class III region achieved a LOD score of 8.1 (P = 1 x 10-9). Nine of 118 affected sibling pairs (7.6%) did not share parental haplotypes identical by descent across the MHC, suggesting that only 31% of the susceptibility to AS is coded by genes linked to the MHC. The maximum non-MHC LOD score obtained was 2.6 (P = 0.0003) for marker D16S422. Conclusion. The results of this study confirm the strong linkage of the MHC with AS, and provide suggestive evidence regarding the presence and location of non-MHC genes influencing susceptibility to the disease.

Is disease severity in ankylosing spondylitis genetically determined?

Objective. To assess the role of genes and the environment in determining the severity of ankylosing spondylitis. Methods: One hundred seventy-three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent-child pairs, 20 families with both first- and second-degree relatives affected, and 7 families with only second-degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease duration and age at onset were also studied. Variance-components modeling was used to determine the genetic and environmental components Contributing to familiality of the traits examined, and complex segregation analysis was performed to assess different disease models. Results. Both the disease activity and functional capacity as assessed by the BASDAI and the BASFI, respectively, were found to be highly familial (BASDAI familiality 0.51 [P = 10-4], BASFI familiality 0,68 [P = 3 × 10-7]). No significant shared environmental component was demonstrated to be associated with either the BASDAI or the BASFI. Including age at disease onset and duration of disease as covariates made no difference in the heritability assessments. A strong correlation was noted between the BASDAI and the BASFI (genetic correlation 0.9), suggesting the presence of shared determinants of these 2 measures. However, there was significant residual heritability for each measure independent of the other (BASFI residual heritability 0.48, BASDAI 0,36), perhaps indicating that not all genes influencing disease activity influence chronicity. No significant heritability of age at disease onset was found (heritability 0.18; P = 0.2). Segregation studies suggested the presence of a single major gene influencing the BASDAI and the BASFI. Conclusion. This study demonstrates a major genetic contribution to disease severity in ankylosing spondylitis. As with susceptibility to ankylosing spondylitis, shared environmental factors play little role in determining the disease severity.

The X-chromosome and susceptibility to ankylosing spondylitis

Objective. Ankylosing spondylitis (AS) affects 0.25-1.0% of the population, and its etiology is incompletely understood. Susceptibility to this highly familial disease (λ(s) = 58) is primarily genetically determined. There is a significant sex bias in AS, and there are differences in recurrence risk to the offspring of affected mothers and fathers, suggesting that there may be an X-linked recessive effect. We undertook an X- chromosome linkage study to determine any contribution of the X-chromosome to AS susceptibility. Methods. A linkage study of the X-chromosome using 234 affected sibling pairs was performed to investigate this hypothesis. Results. No linkage of the X-chromosome with susceptibility to AS was found. Model- free multipoint linkage analysis strongly excluded any significant genetic contribution (λ ≥1.5) to AS susceptibility encoded on the X-chromosome (logarithm of odds [LOD] <-2.0). Smaller genetic effects (A ≥1.3) were also found to be unlikely (LOD <-1.0). Conclusion. The sex bias in AS is not explained by X-chromosome-encoded genetic effects. The disease model best explaining the sex bias in occurrence and transmission of AS is a polygenic model with a higher susceptibility threshold in females.

Agreement between physiotherapists rating scapular posture in multiple planes in patients with neck pain: Reliability study

Objective Evaluation of scapular posture is an integral component of the clinical assessment of painful neck disorders. The aim of this study was to evaluate agreement between therapist judgements of scapula posture in multiple biomechanical planes in individuals with neck pain. Design Inter-therapist reliability study. Setting Research laboratory. Participants Fifteen participants with chronic neck pain. Main outcome measures Four physiotherapists recorded ratings of scapular orientation (relative to the thorax) in five different scapula postural planes (plane of scapula, sagittal plane, transverse plane, horizontal plane, and vertical plane) under four test conditions (at rest, and during three isometric shoulder conditions) in all participants. Inter-therapist reliability was expressed using both generalized and paired kappa coefficient. Results Following adjustment for expected agreement and the high prevalence of neutral ratings (81%), on average both the generalised kappa (0.37) as well as Cohen's Kappa for the two therapist pairs (0.45 and 0.42) demonstrated only slight to moderate inter-therapist reliability. Conclusions The findings suggest that ratings of scapular posture in individuals with neck pain by visual inspection has only slight to moderate reliability and should only be used in conjunction with other clinical tests when judging scapula function in these patients.

The role of germline polymorphisms in the T-cell receptor in susceptibility to ankylosing spondylitis

The role of germline polymorphisms of the T-cell receptor A/D and B loci in susceptibility to ankylosing spondylitis was investigated by linkage studies using microsatellite markers in 215 affected sibling pairs. The presence of a significant susceptibility gene (lambda ≤ 1.6) at the TCRA/D locus was excluded (LOD score < -2.0). At the TCRB locus, there was weak evidence of the presence of a susceptibility gene (P = 0.01, LOD score 1.1). Further family studies will be required to determine whether this is a true or false-positive finding. It is unlikely that either the TCRA/D or TCRB loci contain genes responsible for more than a moderate proportion of the non-MHC genetic susceptibility to ankylosing spondylitis.