Next-generation sequencing of newborn screening genes: the accuracy of short-read mapping.

Newborn screening programs are an integral part of public health systems aiming to save lives and improve the quality of life for infants with treatable disorders. Technological advancements have driven the expansion of newborn screening programs in the last two decades and the development of fast, accurate next-generation sequencing technology has opened the door to a range of possibilities in the field. However, technological challenges with short-read next-generation sequencing technologies remain significant in highly homologous genomic regions such as pseudogenes or paralogous genes and need to be considered when implemented in screening programs. Here, we simulate 50 genomes from populations around the world to test the extent to which high homology regions affect short-read mapping of genes related to newborn screening disorders and the impact of differential read lengths and ethnic backgrounds. We examine a 158 gene screening panel directly relevant to newborn screening and identify gene regions where read mapping is affected by homologous genomic regions at different read lengths. We also determine that the patient's ethnic background does not have a widespread impact on mapping accuracy or coverage. Additionally, we identify newborn screening genes where alternative forms of sequencing or variant calling pipelines should be considered and demonstrate that alterations to standard variant calling can retrieve some formerly uncalled variants.

No influence of sugar, snacks and fast food intake on the degree of obesity or treatment effect in childhood obesity.

BACKGROUND: Increased consumption of sweetened beverages has previously been linked to the degree of childhood obesity. OBJECTIVE: The aim of the present study was to assess whether the intake of sweetened beverages, candy, snacks or fast food at baseline in a multidisciplinary childhood obesity treatment program was associated with the baseline degree of obesity or the treatment effect. METHODS: This prospective study included 1349 overweight and obese children (body mass index standard deviation scores (BMI SDS) ≥ 1.64) enrolled in treatment at The Children's Obesity Clinic, Copenhagen University Hospital Holbaek. The children were evaluated at baseline and after up to 5.9 years of treatment (median 1.3 years). RESULTS: Both boys and girls decreased their BMI SDS during treatment with a mean decrease in boys of 0.35 (p < 0.0001) and in girls of 0.22 (p < 0.0001) after 1 year of treatment. There were no associations between the baseline intake of sweetened beverages, candy, snacks, and/or fast food and BMI SDS at baseline or the change in BMI SDS during treatment. CONCLUSIONS: The intake of sweetened beverages, candy, snacks or fast food when entering a childhood obesity treatment program was not associated with the degree of obesity at baseline or the degree of weight loss during treatment.

1H-MRS measured ectopic fat in liver and muscle is associated with the metabolic syndrome in Danish girls but not in boys with overweight and obesity.

BACKGROUND: The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between MetS and ectopic fat may offer clinical relevance. OBJECTIVES: To investigate the prevalence of MetS, or components hereof, and ectopic fat accumulation in liver and skeletal muscle tissue in children, as well as interactions between these. METHODS: Two-hundred-and-sixteen children and adolescents (95 boys) with overweight/obesity were investigated, as well as 47 controls (22 boys) with normal weight. The assessments included anthropometry, fasting blood biochemistry and blood pressure measurements. Liver and muscle lipid contents were assessed by proton magnetic resonance spectroscopy. RESULTS: We observed an odds ratio in girls with overweight/obesity of 12.2 (95% confidence interval: [3.8; 49.0]) for exhibiting MetS when hepatic steatosis was present, whereas no association was observed in boys with overweight/obesity (odds ratio 0.7 [0.2; 2.7]). The odds ratio of exhibiting MetS in the presence of muscular steatosis was 3.5 [1.4; 9.5] in girls with overweight/obesity and 1.0 [0.2; 5.6] in boys with overweight/obesity. Similar results were seen for girls with overweight/obesity exhibiting concurrent hepatic and muscular steatoses. CONCLUSION: Hepatic and muscular steatoses were associated with MetS among girls, but not among boys with overweight/obesity.

Strong selection on male plumage in a hybrid zone between a hybrid bird species and one of its parents.

Homoploid hybrid speciation (HHS) requires reproductive barriers between hybrid and parent species, despite incomplete reproductive isolation (RI) between the parents. Novel secondary sexual trait values in hybrids may cause prezygotic isolation from both parents, whereas signals inherited by the hybrid from one parent species may cause prezygotic isolation with the other. Here we investigate whether differences in male plumage function as a premating barrier between the hybrid Italian sparrow and one of its parent species, the house sparrow, in a narrow Alpine hybrid zone. Italian sparrow male plumage is a composite mosaic of the parental traits, with its head plumage most similar to its other parent, the Spanish sparrow. We use geographical cline analysis to examine selection on three plumage traits, 75 nuclear single nucleotide polymorphisms (SNPs) and hybrid indices based on these SNPs. Several SNPs showed evidence of restricted introgression in the Alps, supporting earlier findings. Crown colour exhibited the narrowest plumage cline, representing a 37% (range 4-65%) drop in fitness. The cline was too narrow to be due to neutral introgression. Only crown colour was significantly bimodal in the hybrid zone. Bimodality may be due to RI or a major QTL, although fitness estimates suggest that selection contributes to the pattern. We discuss the implications with respect to HHS and the species status of the Italian sparrow.

Single origin of human commensalism in the house sparrow.

The current, virtually worldwide distribution of the house sparrow (Passer domesticus) is a result of its commensal relationship with humans. It has been suggested that long before the advent of agriculture, an early glacial advance resulted in two disjunct ranges of ancestral house sparrows - one in the Middle East and another on the Indian subcontinent. Differentiation during this period of isolation resulted in two major groups of subspecies: the domesticus group and the indicus group. According to this hypothesis, commensalism with humans would have evolved independently in the two regions and at least twice. An alternative hypothesis is that morphological differences between the subspecies represent very recent differentiation, following expansions from a single source. To test between these hypotheses, we analysed genetic variation at the mitochondrial DNA control region and at three nuclear loci from several house sparrow populations in Europe, Asia and North Africa. No differentiation between the indicus and domesticus groups was found, supporting the single origin hypothesis. One of the subspecies in the indicus group, P. d. bactrianus, differs ecologically from other house sparrows in being migratory and in preferentially breeding in natural habitat. We suggest that bactrianus represents a relict population of the ancestral, noncommensal house sparrow. When agricultural societies developed in the Middle East about 10 000 years ago, a local house sparrow population of the bactrianus type adapted to the novel environment and eventually became a sedentary, human commensal. As agriculture and human civilizations expanded, house sparrows experienced a correlated and massive expansion in range and numbers. The pattern of genetic variation analysed here is consistent with this scenario.

Biodegradation studies of selected hydrocarbons from diesel oil.

In-vitro biodegradation of aliphatic and aromatic hydrocarbons present in diesel oil by Pseudomonas fluorescens, Texaco was studied in an aqueous medium. Small aliquots of diesel oil and its aromatic fraction were incubated aerobically for periods of up to seven months and analysed by GC-MS. Biotic losses proved to be greater for aliphatic than aromatic compounds. Most biodegradation occurred within the first 20 d of incubation. The most rapid biodegradation, up to 65% in 8 d, was observed for n-alkanes (C14-C18). The same compounds were also shown to be less affected by abiotic losses. Biodegradation of n-alkanes from diesel oil and diesel oil itself showed first order kinetics for the initial incubation period. Aromatic compounds proved to be resistant to biodegradation and only phenanthrene had been degraded (30%) within 6 months.

What predicts breastfeeding intention in Mexican-American and non-Hispanic white women? Evidence from a national survey.

We examined the effects of a series of predictors on the prepartum intention to breastfeed in both Mexican-American and non-Hispanic white women. A national sample included 430 Mexican-American women and 3659 non-Hispanic white women who had a pregnancy in 1988. Prenatal behavioral, sociodemographic, and biomedical information was obtained through the 1988 National Maternal and Infant Health Survey. Two dependent variables were constructed to identify significant predictors of breastfeeding intention: exclusive versus partial and bottle-feeding, and exclusive and partial versus bottle-feeding. Results from the multiple logistic regression models indicated that advice to breastfeed at prenatal care was the strongest predictor of intentions in both Mexican-American (OR = 2.15, OR = 1.86) and non-Hispanic white mothers (OR = 2.29, OR = 3.61). In Mexican-Americans the father's being Hispanic was negatively associated with breastfeeding intention (OR = 0.63). In non-Hispanic whites the advice to formula feed at the Women, Infants, and Children's nutrition program was a significant negative predictor of breastfeeding intention (OR = 0.33, for exclusive and partial breastfeeding vs exclusive bottle-feeding). These results have important implications for public health policy and practice.