Confirmation of quantitative trait loci affecting fatness in chickens

In this report we describe the analysis of an advanced intercross line (AIL) to confirm the quantitative trait locus (QTL) regions found for fatness traits in a previous study. QTL analysis was performed on chromosomes 1, 3, 4, 15, 18, and 27. The AIL was created by random intercrossing in each generation from generation 2 (G₂) onwards until generation 9 (G₉) was reached. QTL for abdominal fat weight (AFW) and/or percentage abdominal fat (AF%) on chromosomes 1, 3 and 27 were confirmed in the G₉ population. In addition, evidence for QTL for body weight at the age of 5 (BW5) and 7 (BW7) weeks and for the percentage of intramuscular fat (IF%) were found on chromosomes 1, 3, 15, and 27. Significant evidence for QTL was detected on chromosome 1 for BW5 and BW7. Suggestive evidence was found on chromosome 1 for AFW, AF% and IF%, on chromosome 15 for BW5, and on chromosome 27 for AF% and IF%. Furthermore, evidence on the chromosome-wise level was found on chromosome 3 for AFW, AF%, and BW7 and on chromosome 27 for BW5. For chromosomes 4 and 18, test statistics did not exceed the significance threshold.     

广义隐Markov模型在基因识别中的应用

广义隐Markov模型(GHMM)是基因识别的一种重要模型,但是其计算量比传统的隐Markov模型大得多,以至于不能直 接在基因识别中使用。根据原核生物基因的结构特点,提出了一种高效的简化算法,其计算量是序列长度的线性函数。在此 基础上,构建了针对原核生物基因的识别程序GeneMiner,对实际数据的测试表明,此算法是有效的。     

Construction of the model for the Genetic Analysis Workshop 14 simulated data: genotype-phenotype relationships,gene interaction,linkage, association,disequilibrium, and ascertainment effects for a complex phenotype

Background

In order to confirm a previous finding of linkage to alcoholism on chromosome 1 we have carried out a genetic linkage study.

Methods

DNA from eighteen families, densely affected by alcoholism, was used to genotype a set of polymorphic microsatellite markers at loci approximately 10 centimorgans apart spanning the short arm and part of the long arm of chromosome 1. Linkage analyses were performed using the classical lod score and a model-free method. Three different definitions of affection status were defined, these were 1. Heavy Drinking (HD) where affected subjects drank more than the Royal College of Psychiatrists recommended weekly amount. 2. The Research Diagnostic Criteria for alcoholism (RDCA) 3. Alcohol Dependence Syndrome (ADS) as defined by Edwards and Gross (1976) and now incorporated into ICD10 and DSMIV.

Results

Linkage analyses with the markers D1S1588, D1S2134, D1S1675 covering the cytogenetic region 1p22.1-11.2 all gave positive two point and multipoint lods with a maximum lod of 1.8 at D1S1588 (1p22.1) for the RDCA definition of alcoholism. Another lod of 1.8 was found with D1S1653 in the region 1q21.3-24.2 using the HD affection model.

Conclusion

These results both support the presence of linkage in the 1p22.1-11.2 region which was previously implicated by the USA Collaborative Study of the Genetics of Alcoholism (COGA) study and also suggest the presence of another susceptibility locus at 1q21.3-24.2.     

The evolution of antennal courtship in diplazontine parasitoid wasps (Hymenoptera,Ichneumonidae, Diplazontinae)

Background

As predicted by theory, traits associated with reproduction often evolve at a comparatively high speed. This is especially the case for courtship behaviour which plays a central role in reproductive isolation. On the other hand, courtship behavioural traits often involve morphological and behavioural adaptations in both sexes; this suggests that their evolution might be under severe constraints, for instance irreversibility of character loss. Here, we use a recently proposed method to retrieve data on a peculiar courtship behavioural trait, i.e. antennal coiling, for 56 species of diplazontine parasitoid wasps. On the basis of a well-resolved phylogeny, we reconstruct the evolutionary history of antennal coiling and associated morphological modifications to study the mode of evolution of this complex character system.

Results

Our study reveals a large variation in shape, location and ultra-structure of male-specific modifications on the antennae. As for antennal coiling, we find either single-coiling, double-coiling or the absence of coiling; each state is present in multiple genera. Using a model comparison approach, we show that the possession of antennal modifications is highly correlated with antennal coiling behaviour. Ancestral state reconstruction shows that both antennal modifications and antennal coiling are highly congruent with the molecular phylogeny, implying low levels of homoplasy and a comparatively low speed of evolution. Antennal coiling is lost on two independent occasions, and never reacquired. A zero rate of regaining antennal coiling is supported by maximum parsimony, maximum likelihood and Bayesian approaches.

Conclusions

Our study provides the first comparative evidence for a tight correlation between male-specific antennal modifications and the use of the antennae during courtship. Antennal coiling in Diplazontinae evolved at a comparatively low rate, and was never reacquired in any of the studied taxa. This suggests that the loss of antennal coiling is irreversible on the timescale examined here, and therefore that evolutionary constraints have greatly influenced the evolution of antennal courtship in this group of parasitoid wasps. Further studies are needed to ascertain whether the loss of antennal coiling is irreversible on larger timescales, and whether evolutionary constraints have influenced courtship behavioural traits in a similar way in other groups.

     

Pleiotropic effects of the 11p13 locus on developmental verbal dyspraxia and EEG centrotemporal sharp waves

We recently showed genomewide linkage of centrotemporal sharp waves (CTS) in classic Rolandic epilepsy (RE) families to chromosome 11p13, and fine‐mapped this locus to variants in the ELP4 gene. Speech sound disorder (SSD) is a common comorbidity in RE subjects, of unknown etiology, which co‐aggregates in family members in a manner that could hypothetically be explained by shared underlying genetic risk with CTS. Furthermore, the neural mechanism of SSD is unknown, although individuals with rare, Mendelian forms of RE are described with severe verbal and oromotor apraxia. We therefore first performed genomewide linkage analysis for SSD, operationally defined as clinical history consistent with ICD‐10 speech articulation disorder, in 38 families singly ascertained through a proband with RE. We tested the hypothesis of shared genetic risk with CTS at the 11p13 locus. In the second part of the study we used computerized acoustic analysis of recorded speech to test the hypothesis of dyspraxia as a mechanism for SSD in a smaller subset of RE probands and relatives. In two‐point and multipoint LOD score analysis, we found that evidence for linkage to the 11p13 locus increased substantially when the phenotype was broadened from CTS to CTS/SSD. In multipoint analysis, the LOD score rose by 3.2 to HLOD 7.54 at D11S914 for CTS/SSD, the same marker at which multipoint linkage maximized for CTS alone. Non‐parametric, affected‐only methods in a sub‐set of the data provide further confirmatory evidence for pleiotropy. In acoustic analysis there were voice‐onset time abnormalities in 10/18 RE probands, 8/16 siblings and 5/15 parents, providing evidence of breakdown in the spatial/temporal properties of speech articulation consistent with a dyspraxic mechanism. The results from genetic and physiological studies suggest a pleiotropic role for the 11p13 locus in the development of both SSD and CTS, and also indicate a dyspraxic mechanism for the SSD linked to 11p13. Taken together, these data strongly support a neurodevelopmental origin for classic RE.     

An alternative foundation for the planning and evaluation of linkage analysis. I. Decoupling "error probabilities" from "measures of evidence"

The lod score, which is based on the likelihood ratio (LR), is central to linkage analysis. Users interpret lods by translating them into standard statistical concepts such as p values, alpha levels and power. An alternative statistical paradigm, the Evidential Framework, in contrast, works directly with the LR. A key feature of this paradigm is that it decouples error probabilities from measures of evidence. We describe the philosophy behind and the operating characteristics of this paradigm--based on new, alternatively-defined error probabilities. We then apply this approach to linkage studies of a genetic trait for: I. fully informative gametes, II. double backcross sibling pairs, and III. nuclear families. We consider complete and incomplete penetrance for the disease model, as well as using an incorrect penetrance. We calculate the error probabilities (exactly for situations I and II, via simulation for III), over a range of recombination fractions, sample sizes, and linkage criteria. We show how to choose linkage criteria and plan linkage studies, such that the probabilities of being misled by the data (i.e. concluding either that there is strong evidence favouring linkage when there is no linkage, or that there is strong evidence against linkage when there is linkage) are low, and the probability of observing strong evidence in favour of the truth is high. We lay the groundwork for applying this paradigm in genetic studies and for understanding its implications for multiple tests.     

钙离子对PSII颗粒放氧活性的影响

外加5 mmol/L Ca~(2 )可以使菠菜PSⅡ颗粒的放氧活性增高。PSⅡ颗粒经EGTA透析、低pH值、光照、2 mol/L NaCl等处理后,放氧活性下降,同时,这些颗粒的钙含量也相应降低。但当外加 5 mmol/L Ca~(2 )时,可使这些颗粒全部或部分地恢复放氧活性。PSⅡ颗粒中存在的钙对放氧起着重要作用;钙在PSⅡ颗粒中的结合位点不止一个,其结合状态有紧密和松散之别。     

On the empirical choice of the time window for restricted mean survival time

The t-year mean survival or restricted mean survival time (RMST) has been used as an appealing summary of the survival distribution within a time window [0, t]. RMST is the patient's life expectancy until time t and can be estimated nonparametrically by the area under the Kaplan-Meier curve up to t. In a comparative study, the difference or ratio of two RMSTs has been utilized to quantify the between-group-difference as a clinically interpretable alternative summary to the hazard ratio. The choice of the time window [0, t] may be prespecified at the design stage of the study based on clinical considerations. On the other hand, after the survival data have been collected, the choice of time point t could be data-dependent. The standard inferential procedures for the corresponding RMST, which is also data-dependent, ignore this subtle yet important issue. In this paper, we clarify how to make inference about a random “parameter.” Moreover, we demonstrate that under a rather mild condition on the censoring distribution, one can make inference about the RMST up to t, where t is less than or even equal to the largest follow-up time (either observed or censored) in the study. This finding reduces the subjectivity of the choice of t empirically. The proposal is illustrated with the survival data from a primary biliary cirrhosis study, and its finite sample properties are investigated via an extensive simulation study.