Genetic and nongenetic bases for the L-shaped distribution of quantitative trait loci effects.

The L-shaped distribution of estimated QTL effects (R(2)) has long been reported. We recently showed that a metabolic mechanism could account for this phenomenon. But other nonexclusive genetic or nongenetic causes may contribute to generate such a distribution. Using analysis and simulations of an additive genetic model, we show that linkage disequilibrium between QTL, low heritability, and small population size may also be involved, regardless of the gene effect distribution. In addition, a comparison of the additive and metabolic genetic models revealed that estimates of the QTL effects for traits proportional to metabolic flux are far less robust than for additive traits. However, in both models the highest R(2)'s repeatedly correspond to the same set of QTL.

Optimisation of enzyme concentrations for unbranched reaction chains: the concept of combined response coefficient.

In the metabolic control theory, the control coefficient is a key parameter in quantifying the sensitivity of the flux towards an infinitesimal variation of enzyme activity. This concept does not apply just as it is for variations of enzyme concentrations whenever there is spatial, energy or resources limitations in the cell. Due to constraint on total enzyme concentration, the variation of concentration of any given enzyme may affect the concentrations of other enzymes. To take into account these correlations between enzyme concentrations, we propose the concept of "combined response coefficient". Its definition is similar to that of the control coefficient, but its mathematical expression is different. Its range of variation is from -infinity to +1, the null value corresponding to optimum enzyme concentration, i.e. to concentrations that maximise the flux, and the negative values to concentrations beyond the optimum value. A summation property could be derived using a simple weighting of the combined response coefficients, the sum of the weighed coefficient being 0.

Fluxes and metabolic pools as model traits for quantitative genetics. I. The L-shaped distribution of gene effects.

The fluxes through metabolic pathways can be considered as model quantitative traits, whose QTL are the polymorphic loci controlling the activity or quantity of the enzymes. Relying on metabolic control theory, we investigated the relationships between the variations of enzyme activity along metabolic pathways and the variations of the flux in a population with biallelic QTL. Two kinds of variations were taken into account, the variation of the average enzyme activity across the loci, and the variation of the activity of each enzyme of the pathway among the individuals of the population. We proposed analytical approximations for the flux mean and variance in the population as well as for the additive and dominance variances of the individual QTL. Monte Carlo simulations based on these approximations showed that an L-shaped distribution of the contributions of individual QTL to the flux variance (R(2)) is consistently expected in an F(2) progeny. This result could partly account for the classically observed L-shaped distribution of QTL effects for quantitative traits. The high correlation we found between R(2) value and flux control coefficients variance suggests that such a distribution is an intrinsic property of metabolic pathways due to the summation property of control coefficients.

Assessing the impact of introducing laparoscopically assisted vaginal hysterectomy into a community-based gynecology practice.

This study was undertaken to determine the effects of introducing laparoscopically assisted vaginal hysterectomy (LAVH) into a community-based gynecology practice on the route of hysterectomy, operating time, patient costs, length of hospitalization, and morbidity, including complications and blood loss. All patients in the author's practice who had hysterectomies during the 10 months before completion of an advanced operative laparoscopy course were compared with the patients having a hysterectomy in the 10 months after the course. The route of hysterectomy, surgery time, length of hospital stay, preoperative and postoperative hemoglobin, uterine weight, diagnoses, and historical clinical data were compared between the two groups using a level of significance (alpha = 0.01) to assess statistical relevance. The rate of vaginal hysterectomy was remarkably higher in the AFTER group (53.2%, n = 62) vs the BEFORE group (27.7%, n = 65). The AFTER group had a significantly shorter hospital stay (3.4 days +/- 1.22 vs 4 days +/- 1.26, p < or = 0.01) but a much longer surgery time (115.9 min +/- 38.98 vs 80.1 min +/- 27.95, p < or = 0.01). There was no real difference in complication rates or fall in hemoglobin between the two groups. When LAVH was compared with TAH, the LAVH patients tended to be younger (37.4 +/- 8.66 vs 46.2 +/- 16.5 years) and to have a shorter hospital stay (3.1 +/- 0.99 vs 4.1 +/- 1.27 days), a longer surgery time (114.9 +/- 37.45 vs 85.3 +/- 33.74 min), and a bigger hospital bill ($6245 +/- 380 vs $5140 +/- 410) than patients with TAH.(ABSTRACT TRUNCATED AT 250 WORDS)