Genome-wide association study of Tourette's syndrome.

Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.

Transamination of 2-oxo-4-[methylthio]butanoic acid in chicken tissues.

The keto acid 2-oxo-4[methylthio]butanoic acid (OMTB) is an intermediate in the conversion of synthetic feed grade methionine sources to L-methionine in vivo in poultry and other animals. Because methionine sources are utilized by the chick with considerably less than 100% efficiency as sources of L-methionine, it is important to determine what metabolic process may limit the utilization of these sources. Because OMTB is converted to L-methionine by transamination, a study was conducted to determine which amino acids might serve as nitrogen donors in the conversion of OMTB to L-methionine in the chicken. Dialyzed tissue homogenates, mitochondria, and cytosol from liver, kidney, intestine, and skeletal muscle were incubated with OMTB and individual L-amino acids (isoleucine, leucine, valine, glutamic acid, aspartic acid, alanine, glutamine, asparagine, and phenylalanine) and the methionine that accumulated was determined by ion exchange chromatography. Tissues differed in the conversion of OMTB to methionine: kidney was most active, liver and intestinal mucosa were intermediate, and skeletal muscle had lowest activity. All amino acids supported methionine synthesis. Branched-chain amino acids and glutamic acid were the most effective substrates in tissue cytosols except in intestinal mucosa, in which asparagine was also effective. The preferred substrates in mitochondria were glutamate in liver mitochondria, isoleucine and alanine in kidney mitochondria, and branched-chain amino acids and glutamic acid in skeletal muscle mitochondria. All amino acids except alanine supported methionine synthesis from OMTB in mitochondria of intestinal mucosa. We conclude that a wide variety of amino acids can serve as substrates for transamination of OMTB in the chicken, and that the availability of nitrogen donors is unlikely to be a limiting factor in the conversion of OMTB to methionine.

Threonine requirement and threonine imbalance in broiler chickens.

Three experiments were conducted to determine the effect of excess dietary protein on threonine requirement of broiler chicks to 14 d of age (Experiments 1 and 2) and to determine the threonine requirement from 16 to 28 d of age (Experiment 3). Two dietary protein levels were used in Experiments 1 and 2:20% CP in a threonine-limiting basal diet containing wheat, peanut meal, and selected amino acids and 25% CP in the same basal diet supplemented with a mixture of amino acids lacking threonine. A threonine-limiting 25% CP diet based on corn, soybean meal, and amino acids was also included in Experiment 2. The threonine requirement of chicks from 16 to 28 d of age was determined using a single CP level (20%) in Experiment 3. Threonine requirements were estimated by broken line regression analysis of weight gain and feed efficiency. Threonine requirements based on weight gain were 7.7 and 6.7 g/kg of diet in Experiments 1 and 2, respectively, for chicks receiving the 20% CP diets. The requirements increased to 8.6 and 8.2 g/kg, respectively, for chicks fed the 25% CP diets based on wheat, peanut meal, and amino acids. The requirement for maximum weight gain of chicks fed 25% CP based on corn, soybean meal, and amino acids was 7.7 g/kg of diet. However, chicks ate more of this diet, and on an intake basis, the requirement of the chicks fed the 25% CP diets based on wheat and peanut meal or corn and soybean meal did not differ. Requirements based on feed efficiency were equal to, or less than, those based on weight gain in Experiments 1 and 2. Body moisture and fat contents were affected by dietary CP level (P < .01), ingredient composition (P < .01), and threonine content (P < .05). Estimates of threonine requirements based on regression analysis of plasma threonine concentrations were higher than those based on weight gain or feed efficiency. The threonine requirements of chicks fed a 20% CP diet from 16 to 28 d of age were 6.3 and 6.9 g/kg of diet based on weight gain and feed efficiency, respectively.

Effects of selected minerals on acid-base balance and tibial dyschondroplasia in broiler chickens.

Experiments were conducted to determine the relative acidogenicities of several anions, including chloride, sulfate, and mono-, di-, and tribasic phosphate in commercial broiler chickens. Graded levels (80 and 160 meq/kg of diet in two experiments; 50, 100, and 150 meq/kg in a third experiment) of all anions were substituted as calcium salts on a molar equivalent basis for calcium carbonate in a semipurified diet. All diets contained equivalent amounts of calcium. The occurrence of tibial dyschondroplasia was determined by visual scoring of the epiphyseal growth plate in the distal end of the tibiotarsus. None of the anions added to the diet at levels of 160 meq/kg or less affected body weight or feed consumption. A higher level of chloride (240 meq/kg) that was utilized in some experiments decreased weight gain by 16 to 22%. All anions except tribasic phosphate resulted in reduced blood pH or bicarbonate concentrations or both. Monobasic phosphate was more acidogenic than dibasic phosphate and sulfate and chloride was the most acidogenic of all mineral anions. All anions including tribasic phosphate increased the severity of tibial dyschondroplasia. There was no consistent relationship between blood pH, bicarbonate concentration, or partial pressure of CO2 and the severity of tibial dyschondroplasia.