Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis.

Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10(-7)) and myosin IIIB (MYO3B; P=5.4 × 10(-6)). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.

Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis.

BACKGROUND Hormonal effects of soy and isoflavones have been investigated in numerous trials with equivocal findings. We aimed to systematically assess the effects of soy and isoflavones on circulating estrogen and other hormones in pre- and post-menopausal women. METHODS The Cochrane Library, MEDLINE and EMBASE (plus reviews and experts) were searched to December 2007. Inclusion of randomized or residential crossover trials of soy or isoflavones for 4 or more weeks on estrogens, SHBG, FSH, LH, progesterone and thyroid hormones in women was assessed independently in duplicate. Six percent of papers assessed were included. Data concerning participants, interventions, outcomes, potential effect modifiers and trial quality characteristics were extracted independently in duplicate. RESULTS Forty-seven studies (11 of pre-, 35 of post- and 1 of perimenopausal women) were included. In premenopausal women, meta-analysis suggested that soy or isoflavone consumption did not affect primary outcomes estradiol, estrone or SHBG concentrations, but significantly reduced secondary outcomes FSH and LH [by approximately 20% using standardized mean difference (SMD), P = 0.01 and 0.05, respectively]. Menstrual cycle length was increased by 1.05 days (95% CI 0.13, 1.97, 10 studies). In post-menopausal women, there were no statistically significant effects on estradiol, estrone, SHBG, FSH or LH, although there was a small statistically non-significant increase in total estradiol with soy or isoflavones ( approximately 14%, SMD, P = 0.07, 21 studies). CONCLUSIONS Isoflavone-rich soy products decrease FSH and LH in premenopausal women and may increase estradiol in post-menopausal women. The clinical implications of these modest hormonal changes remain to be determined.

Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review.

UNLABELLED: We conducted a systematic review of genetic association studies for osteoarthritis of the peripheral joints (OA) and spinal degenerative disease (SDD). Electronic searches were carried out for any English language article reporting on a gene association study for either OA or SDD published up until the end of 2006. A team of seven reviewers used a standardised template to extract data in duplicate. In all, 90 studies fulfilled our inclusion criteria, reporting a total of 94 significant associations from 83 different genes. We found relatively few instances in which a specific gene-disease association had been analysed by more than one study, and there were 14 cases in which significant associations were replicated in independent studies (at joints associated with the AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, HFE, IL1A, IL1RN, PTGS2 and VDR genes). METHOD: logical and reporting problems were widespread, including failure to report full results, missing population details, multiple testing, and over-reliance on subgroup analysis. In summary, the complex phenotypes of OA and SDD may have made it difficult for researchers to focus their efforts. The field is dominated by isolated analyses of disparate potential associations, a problem that is amplified by the frequent analysis of different polymorphisms within individual genes. Flaws in study methodology and interpretation undoubtedly increase the risk of publication bias. Closer adherence to published recommendations (in particular those produced by HuGENet) will help to ensure that future studies are well-designed and build on current understanding, rather than simply adding to the growing bank of potential associations.

Phased infectivity in Heterorhabditis megidis: the effects of infection density in the parental host and filial generation.

Entomopathogenic nematodes can develop through two or more generations in the cadavers of killed insect hosts. Non-feeding infective juveniles from each generation emerge and may spend prolonged periods searching for a new host. The infectivity of the infective juveniles of Heterorhabditis megidis varies with time after emergence and may not reach a maximum until several weeks have passed. 'Phased infectivity' hypotheses propose that this pattern is adaptive, tending to reduce competition in new hosts. Here we provide further evidence that infectivity is phased in H. megidis. In addition, we show that the basic pattern is modified by infection density in the parental host and by filial generation. Two general patterns were observed: first, infective juveniles that developed under the least crowded conditions (F(1) infective juveniles produced in hosts infected with 16 parent nematodes) reached maximum infectivity after only 15 days, compared to 27 or 39 days for infective juveniles that developed under more crowded conditions (F(1) produced in hosts infected with 103 or 424 parent nematodes or F(2) infective juveniles). Second, infective juveniles had lower infectivity overall when produced under the most crowded conditions (F(2) versus F(1); highest versus lowest infection density). We propose that while lower overall infectivity is a necessary consequence of limited resource availability during infective juvenile development, the difference in the timing of peak infectivity reflects a shift in the fitness gains associated with being maximally infective either 'early' or 'late'. F(1) infective juveniles emerge several days before F(2) infective juveniles, and we suggest that filial generation and infection density in the parental host function as indicators of the potential risk of competition within new hosts.

Density-dependent fecundity and infective juvenile production in the entomopathogenic nematode, Heterorhabditis megidis.

The entomopathogenic nematode Heterorhabditis megidis may undergo several rounds of reproduction within a single host. Infective juveniles (IJs) are formed within each generation during a process referred to as endotokia matricida, which involves the progressive consumption of the parent hermaphrodite or female by the developing IJs prior to emergence from the host cadaver. The present study examines the extent to which within-host population dynamics exhibit density-dependent variation. Particular attention is paid to the effect of infection density on the relative production of IJs and 'normal', non-infective offspring within each generation and on the emergence of the IJs from the host. Fecundity was found to be negatively density dependent across generations. However, at high infection density the first generation hermaphrodites invested relatively more in IJs at the expense of producing non-infective offspring. It is suggested that this pattern resulted from an adaptive, phenotypically plastic allocation of reproductive investment between offspring types in response to increased competition. The F1 and F2 IJs were also shown to emerge from the host in relatively discrete pulses.

Male calling song provides a reliable signal of immune function in a cricket.

A critical prediction of the immunocompetence handicap hypothesis is that the expression of secondary sexual traits should be positively correlated with pathogen resistance ability This correlation is necessary if females are to be able to use a particular sexual trait as an indicator of a male's resistance ability. In this study we document a positive correlation between a sexually selected component of the calling song of male house crickets (the number of syllables per chirp) and haemocyte load, an important determinant of the ability to encapsulate pathogens in insects. The results indicate that, by favouring males which produce more syllables per chirp, females may also select males with higher pathogen resistance ability, potentially generating either direct or indirect selection on female mating preferences.