ABSTRACT
PURPOSE: To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS). METHODS: Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing. RESULTS: NBS genes are generally well covered by WGS. There is a median of one (range: 0-6) database-annotated pathogenic variant in the NBS genes per infant. Results of WGS and NBS in detecting 28 state-screened disorders and four hemoglobin traits were concordant for 88.6% of true positives (n = 35) and 98.9% of true negatives (n = 45,757). Of the five infants affected with a state-screened disorder, WGS identified two whereas NBS detected four. WGS yielded fewer false positives than NBS (0.037 vs. 0.17%) but more results of uncertain significance (0.90 vs. 0.013%). CONCLUSION: WGS may help rule in and rule out NBS disorders, pinpoint molecular diagnoses, and detect conditions not amenable to current NBS assays.
Subject(s)
Genetic Predisposition to Disease , Genome, Human , Neonatal Screening/methods , Sequence Analysis, DNA/methods , Cohort Studies , Female , Genetic Variation , Humans , Infant, Newborn , Male , Sensitivity and SpecificityABSTRACT
San Antonio, Texas, was one of the first metropolitan areas where 2009 pandemic influenza A (H1N1) virus (pH1N1) was detected. Identification of laboratory-confirmed pH1N1 in 2 students led to a preemptive 8-day closure of their high school. We assessed transmission of pH1N1 and changes in adoption of nonpharmaceutical interventions (NPIs) within households of students attending the affected school. Household secondary attack rates were 3.7% overall and 9.1% among those 0-4 years of age. Widespread adoption of NPIs was reported among household members. Respondents who viewed pH1N1 as very serious were more likely to adopt certain NPIs than were respondents who viewed pH1N1 as not very serious. NPIs may complement influenza vaccine prevention programs or be the only line of defense when pandemic vaccine is unavailable. The 2009 pandemic provided a unique opportunity to study NPIs, and these real-world experiences provide much-needed data to inform pandemic response policy.