Highly variable incidence of cystic fibrosis and different mutation distribution among different Jewish ethnic groups in Israel

The incidence of cystic fibrosis (CF) and the frequency of disease-causing mutations varies among different ethnic and geographic populations. The Jewish population around the world is comprised of two major ethnic groups; Ashkenazi and non-Ashkenazi. The latter is further classified according to country of origin. In this study, we analyzed the incidence of CF and the distribution of CF mutations in the general Jewish population in Israel and in most of the Jewish ethnic subgroups. The disease frequency varies considerably among the latter. Among Ashkenazi Jews, the frequency of CF is 13300, which is similar to the frequency in most Caucasian populations. Among non-Ashkenazi Jews, the disease occurs at a similar frequency among Jews from Libya (12700), Georgia (12700), Greece and Bulgaria (12400), but is rare in Jews from Yemen (18800), Morocco (115000), Iraq (132000), and Iran (139000). So far, only 12 mutations have been identified in Israeli Jews, and this enables the identification of 91% of the CF chromosomes in the entire Jewish CF population. However, in each Jewish ethnic group, the disease is caused by a different repertoire of mutations. The frequency of identified mutations is high in Ashkenazi Jews (95%), and in Jews originating from Tunisia (100%), Libya (91%), Turkey (90%), and Georgia (88%). However, a lower frequency of mutations can be identified in Moroccan (85%), Egyptian (50%), and Yemenite (0%) Jews. For genetic counseling of a Jewish individual, it is necessary to calculate the residual risk according to ethnic origin. Carrier screening of healthy Jewish individuals is currently feasible for Ashkenazi Tunisian, Libyan, Turkish, and Georgian Jews. These results provide the required information for genetic counseling of Jewish CF families and screening programs of Jewish populations worldwide.     

The VIL gene CRAWLING ELEPHANT controls maturation and differentiation in tomato via polycomb silencing

VERNALIZATION INSENSITIVE 3-LIKE (VIL) proteins are PHD-finger proteins that recruit the repressor complex Polycomb Repressive Complex 2 (PRC2) to the promoters of target genes. Most known VIL targets are flowering repressor genes. Here, we show that the tomato VIL gene CRAWLING ELEPHANT (CREL) promotes differentiation throughout plant development by facilitating the trimethylation of Histone H3 on lysine 27 (H3K27me3). We identified the crel mutant in a screen for suppressors of the simple-leaf phenotype of entire (e), a mutant in the AUX/IAA gene ENTIRE/SlIAA9, involved in compound-leaf development in tomato. crel mutants have increased leaf complexity, and suppress the ectopic blade growth of e mutants. In addition, crel mutants are late flowering, and have delayed and aberrant stem, root and flower development. Consistent with a role for CREL in recruiting PRC2, crel mutants show drastically reduced H3K27me3 enrichment at approximately half of the 14,789 sites enriched in wild-type plants, along with upregulation of many underlying genes. Interestingly, this reduction in H3K27me3 across the genome in crel is also associated with gains in H3K27me3 at a smaller number of sites that normally have modest levels of the mark in wild-type plants, suggesting that PRC2 activity is no longer limiting in the absence of CREL. Our results uncover a wide role for CREL in plant and organ differentiation in tomato and suggest that CREL is required for targeting PRC2 activity to, and thus silencing, a specific subset of polycomb targets.     

Adaptation to hot climate and strategies to alleviate heat stress in livestock production

Despite many challenges faced by animal producers, including environmental problems, diseases, economic pressure, and feed availability, it is still predicted that animal production in developing countries will continue to sustain the future growth of the world's meat production. In these areas, livestock performance is generally lower than those obtained in Western Europe and North America. Although many factors can be involved, climatic factors are among the first and crucial limiting factors of the development of animal production in warm regions. In addition, global warming will further accentuate heat stress-related problems. The objective of this paper was to review the effective strategies to alleviate heat stress in the context of tropical livestock production systems. These strategies can be classified into three groups: those increasing feed intake or decreasing metabolic heat production, those enhancing heat-loss capacities, and those involving genetic selection for heat tolerance. Under heat stress, improved production should be possible through modifications of diet composition that either promotes a higher intake or compensates the low feed consumption. In addition, altering feeding management such as a change in feeding time and/or frequency, are efficient tools to avoid excessive heat load and improve survival rate, especially in poultry. Methods to enhance heat exchange between the environment and the animal and those changing the environment to prevent or limit heat stress can be used to improve performance under hot climatic conditions. Although differences in thermal tolerance exist between livestock species (ruminants > monogastrics), there are also large differences between breeds of a species and within each breed. Consequently, the opportunity may exist to improve thermal tolerance of the animals using genetic tools. However, further research is required to quantify the genetic antagonism between adaptation and production traits to evaluate the potential selection response. With the development of molecular biotechnologies, new opportunities are available to characterize gene expression and identify key cellular responses to heat stress. These new tools will enable scientists to improve the accuracy and the efficiency of selection for heat tolerance. Epigenetic regulation of gene expression and thermal imprinting of the genome could also be an efficient method to improve thermal tolerance. Such techniques (e.g. perinatal heat acclimation) are currently being experimented in chicken.     

Adaptive energy metabolism in four chromosomal species of subterranean mole rats

Summary Gross energy intake and apparent dry matter digestibility of animals fed carrots ad lib in the laboratory, were measured in the four chromosomal species of the Spalax ehrenbergi superspecies in Israel. Gross energy intake of 132.8 and 155.9 kJ/day was measured for the 2n=52 and 2n=58 chromosomal mesic species, while in the 2n=54 and 2n=60 chromosomal xeric species it measured only 80.3 and 75.0 kJ/day, respectively. Dry matter digestibility ranged between 92.3 and 95.6% in thefour chromosomal species. The differences in gross energy intake between the mesic and xeric species, appeared to reflect adaptive energy metabolism variation associated with geographic variation in climate, habitat productivity, and food availability.     

Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease

Only about 30% of the cystic fibrosis chromosomes in the Israeli cystic fibrosis patient populations carry the major CF mutation (delta F508). Since different Jewish ethnic groups tended to live as closed isolates until recent times, high frequencies of specific mutations are expected among the remainder cystic fibrosis chromosomes of these ethnic groups. Genetic factors appear to influence the severity of the disease. It is therefore expected that different mutations will be associated with either severe or mild phenotype. Direct genomic sequencing of exons included in the two nucleotide-binding folds of the putative CFTR protein was performed on 119 Israeli cystic fibrosis patients from 97 families. One sequence alteration which is expected to create a termination at residue 1282 (W1282X) was found in 63 chromosomes. Of 95 chromosomes, 57 (60%) are of Ashkenazi origin. Together with the delta F508 (23% in this group), G542X, N1303K, and 1717-1G----A mutations, the identification of 92% of cystic fibrosis chromosomes of Ashkenazi origin becomes possible. Patients homozygous for the W1282X mutation (n = 16) and patients heterozygous for the delta F508 and W1282X mutations (n = 22) had similarly severe disease, reflected by pancreatic insufficiency, high incidence of meconium ileus (37% and 27%, respectively), early age at diagnosis, poor nutritional status, and variable pulmonary function. In conclusion, the W1282X mutation is the most common cystic fibrosis mutation in the Ashkenazi Jewish patient population in Israel. This nonsense mutation is associated with presentation of severe disease.     

Early-age heat exposure affects skeletal muscle satellite cell proliferation and differentiation in chicks

Exposure of young chicks to thermal conditioning (TC; i.e., 37 degrees C for 24 h) resulted in significantly improved body and muscle growth at a later age. We hypothesized that TC causes an increase in satellite cell proliferation, necessary for further muscle hypertrophy. An immediate increase was observed in satellite cell DNA synthesis in culture and in vivo in response to TC of 3-day-old chicks to levels that were significantly higher than those of control chicks. This was accompanied by a marked induction of insulin-like growth factor-I (IFG-I), but not hepatocyte growth factor in the breast muscle. No significant difference between treatments in plasma IGF-I levels was observed. A marked elevation in muscle regulatory factors on day 5, followed by a decline in cell proliferation on day 6 together with continuous high levels of IGF-I in the TC chick muscle may indicate accelerated cell differentiation. These data suggest a central role for IGF-I in the immediate stimulation of satellite cell myogenic processes in response to heat exposure.     

Early age cold conditioning in broiler chickens (Gallus domesticus): thermotolerance and growth responses

The influence of short repetitive cold exposure at an early age (cold conditioning—exposure to 15°C for 3 h at 3 and 4 days of age) on chickens’ thermotolerance during cold challenge (15°C) at 21 days of age was examined. The first cold exposure elicited a dramatic decline in body temperature (T_b) and a significant elevation in stress response (plasma corticosterone concentration); the second cold exposure resulted in moderate T_b and stress responses. Thereafter, the corticosterone concentration remained at a significantly lower level. Acute cold challenge of conditioned broilers at 21 days of age revealed better T_b and stress recovery during the first 24 h, and a significantly lower mortality rate thereafter. Conditioned chickens exposed to optimal conditions (22°C) achieved significantly higher body weights than others. It may be concluded that early cold conditioning improves thermotolerance in broiler chickens in later life.     

Apoptotic cells represent a dynamic stem cell niche governing proliferation and tissue regeneration

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The effect of temperature on caecal fermentation processes in a poikilothermic mammal, Heterocephalus glaber

1. 1.|The effect of temperature on caecal function was examined in the naked mole-rat Heterocephalus glaber, a poikilothermic mammal, which consumes a high proportion of fibre in its natural diet.

2. 2.|The temperature of optimal caecal function was determined from fermentation data measure at three specifically chosen temperatures (28, 33 and 40°C).

3. 3.|There was no significant difference between gas production at 33 and 40°C, however, gas production was significantly lower at 28°C.

4. 4.|The relative proportions of the gases produced were markedly different at 33 and 40°C (P ≤ 0.01). More methane and hydrogen were produced at 33°C than at 40°C.

5. 5.|These data suggest that microbial organisms within the caecum were active and functioning more effectively at 33°C (the preferred body temperature of the naked mole-rat) than at the other two temperatures.