Whole-genome sequencing expands diagnostic utility and improves clinical management in paediatric medicine

The standard of care for first-Tier clinical investigation of the aetiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy-number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single-nucleotide variant (SNV) mutations. Whole-genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilised WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a fourfold increase in diagnostic rate over CMA (8%; P value = 1.42E - 05) alone and more than twofold increase in CMA plus targeted gene sequencing (13%; P value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harbouring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis

Effect of nutrition education during puberty on nutritional knowledge and behavior of secondary School female students in Birjand in 2012

Background and Aim: Growth spurt during adolescence, particularly the occurrence of menstruation in girls, increases their nutritional needs. The present study aimed at determining the effect of nutrition education on nutritional knowledge and Behavior of secondary school female students in the city of Birjand. Materials and Methods: In this quasi-experimental study, 120 second grade secondary students in Birjand in 2012 were selected through two-stage cluster sampling method and were randomly divided into intervention and control groups. Data collection tool was a questionnaire which was completed by the students both before and one month after intervention. The obtained data was analyzed by means of descriptive and analytical statistics including chi-square, independent and paired t-tests, and ANOVA at the significant level of 0.05 using SPSS software (V:16). Results: Mean scores of nutritional knowledge in the intervention group after education increased from 21.35±4.57 to 26.66±4.4 (P>0.001) and their mean performance increased from 1.84±7.39 to 1.86±8.31 (P<0.04). A significant difference in mean scores of knowledge between the control group and the intervention group was observed (P<0.05). However, performance mean difference between the two groups was not significant. Conclusion: Education through lecture and asking/answering questions can significantly increase adolescents’ awareness and to some extent, their nutritional performance, although more effective methods are advised to promote the situation

Genetic variation in healthy oldest-old

Individuals who live to 85 and beyond without developing major age-related diseases may achieve this, in part, by lacking disease susceptibility factors, or by possessing resistance factors that enhance their ability to avoid disease and prolong lifespan. Healthy aging is a complex phenotype likely to be affected by both genetic and environmental factors. We sequenced 24 candidate healthy aging genes in DNA samples from 47 healthy individuals aged eighty-five years or older (the 'oldest-old'), to characterize genetic variation that is present in this exceptional group. These healthy seniors were never diagnosed with cancer, cardiovascular disease, pulmonary disease, diabetes, or Alzheimer disease. We re-sequenced all exons, intron-exon boundaries and selected conserved non-coding sequences of candidate genes involved in aging-related processes, including dietary restriction (PPARG, PPARGC1A, SIRT1, SIRT3, UCP2, UCP3), metabolism (IGF1R, APOB, SCD), autophagy (BECN1, FRAP1), stem cell activation (NOTCH1, DLL1), tumor suppression (TP53, CDKN2A, ING1), DNA methylation (TRDMT1, DNMT3A, DNMT3B) Progeria syndromes (LMNA, ZMPSTE24, KL) and stress response (CRYAB, HSPB2). We detected 935 variants, including 848 single nucleotide polymorphisms (SNPs) and 87 insertion or deletions; 41% (385) were not recorded in dbSNP. This study is the first to present a comprehensive analysis of genetic variation in aging-related candidate genes in healthy oldest-old. These variants and especially our novel polymorphisms are valuable resources to test for genetic association in models of disease susceptibility or resistance. In addition, we propose an innovative tagSNP selection strategy that combines variants identified through gene re-sequencing- and HapMap-derived SNPs