RESUMO
PURPOSE: To describe the process and assess outcomes for the first 2 years of newborn screening for severe combined immunodeficiency (SCID NBS) in New York State (NYS). METHODS: The NYS algorithm utilizes a first-tier molecular screen for TRECs (T-cell receptor excision circles), the absence of which is indicative of increased risk of immunodeficiency. RESULTS: During the first 2 years, 485,912 infants were screened for SCID. Repeat specimens were requested from 561 premature and 746 non-premature infants with low or borderline TRECs. A total of 531 infants were referred for diagnostic evaluation leading to identification of 10 infants with SCID and 87 with a clinically significant non-SCID abnormality based on flow cytometry or CBC results (positive predictive value 20.3 %). Nine infants were diagnosed with typical SCID and one with leaky SCID. SCID diagnoses included two patients with adenosine deaminase deficiency, three patients with typical and one with leaky IL2RG-related SCID, one patient with IL7Rα-related SCID, and three cases of typical SCID, etiology unknown. TRECs were undetectable in eight of the nine babies with typical SCID. Infants with other non-SCID conditions included 27 patients with a syndrome that included T-cell impairment, 18 of which had DiGeorge syndrome. Seventeen infants had T-cell impairment secondary to another clinically significant condition, and 13 were classified as 'other'. Among 30 infants classified as idiopathic T-cell lymphopenia, 11 have since resolved, and the remainder continues to be followed. One infant with undetectable TRECs had normal follow-up studies. Molecular studies revealed the presence of two changes in the infant's DNA. CONCLUSIONS: Overall, ten infants with SCID were identified during the first 2 years of screening in NYS, yielding an incidence of approximately 1 in 48,500 live births, which is consistent with the incidence observed by other states screening for SCID. The incidence of any clinically significant laboratory abnormality was approximately 1 in 5,000; both estimates are higher than estimates prior to the onset of newborn screening for SCID. Improvements to the NYS algorithm included the addition of a borderline category that reduced the proportion of infants referred for flow cytometric analysis, without decreasing sensitivity. We identified a large number of infants with abnormal TRECs and subsequent idiopathic T-cell lymphopenia. Long-term follow-up studies are needed to determine the prognosis and optimal treatment for this group of patients, some of whom may present with previously unrecognized, transient lymphopenia of infancy.
Assuntos
Triagem Neonatal , Imunodeficiência Combinada Severa/diagnóstico , Algoritmos , Feminino , Testes Genéticos/métodos , Humanos , Imunofenotipagem/métodos , Recém-Nascido , Masculino , Triagem Neonatal/métodos , New York , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Imunodeficiência Combinada Severa/etiologia , Imunodeficiência Combinada Severa/terapiaRESUMO
BACKGROUND: Dried blood spot (DBS) samples have been widely used in newborn screening (NBS) for the early identification of disease to facilitate the presymptomatic treatment of congenital diseases in newborns. As molecular genetics knowledge and technology progresses, there is an increased demand on NBS programs for molecular testing and a need to establish reliable, low-cost methods to perform those analyses. Here we report a flexible, cost-efficient, high-throughput DNA extraction method from DBS adaptable to small- and large-scale screening settings. METHODS: Genomic DNA (g.DNA) was extracted from single 3-mm diameter DBS by the sequential use of red cell lysis, detergent-alkaline, and acid-neutralizing buffers routinely used in whole blood and plant tissue DNA extractions. We performed PCR amplification of several genomic regions using standard PCR conditions and detection methods (agarose gel, melting-curve analysis, TaqMan-based assays). Amplicons were confirmed by BigDye® Terminator cycle sequencing and compared with reference sequences. RESULTS: High-quality g.DNA was extracted from hundreds of DBS, as proven by mutation detection of several human genes on multiple platforms. Manual and automated extraction protocols were validated. Quantification of g.DNA by Oligreen® fluorescent nucleic acid stain demonstrated a normal population distribution closely corresponding with white blood cell counts detected in newborn populations. CONCLUSIONS: High-quality, amplifiable g.DNA is extractable from DBSs. Our method is adaptable, reliable, and scalable to low- and high-throughput NBS at low cost ($0.10/sample). This method is routinely used for molecular testing in the New York State NBS program.
Assuntos
DNA/isolamento & purificação , Teste em Amostras de Sangue Seco/métodos , Análise Custo-Benefício , DNA/sangue , Teste em Amostras de Sangue Seco/economia , Humanos , Recém-Nascido , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Conservation translocations-the intentional movement of animals to restore populations-have increased over the past 30 years to halt and reverse species declines and losses. However, there are many challenges translocated animals face that should be considered for restoration programs to be successful. Understanding how long it takes for translocated animals to acclimate to these challenges and their new landscape is a critical component of post-release population management. Physiological measures such as hormone responses are increasingly used to assess animal responses and acclimation to disturbances including translocation. We determined the physiological acclimation period of elk (Cervus canadensis) translocated to the Missouri Ozarks, USA, as part of a restoration effort. From 2011 to 2013, we translocated 108 GPS-radio-collared elk from Kentucky, USA, to Missouri, USA, and collected faecal samples for glucocorticoid metabolite extraction to use as an indicator of physiological acclimation. We modelled the response of population-wide faecal glucocorticoid metabolites (fGCMs) across the initial 9 years of the restoration in response to days following release and additional site-specific covariates. Presence of white-tailed deer (Odocoileus virginianus) hunts and monthly precipitation levels were positively and negatively associated with fGCM levels, respectively. Concurrent with influences from site-specific conditions on the release landscape, fGCM levels declined following release. We identified a breakpoint in fGCM decline at ~42 days following translocation releases suggesting elk acclimated physiologically relatively quickly compared to other species. The fast physiological acclimation by Missouri elk suggests effective use of temporary post-release management efforts. Determining how quickly animals acclimate following translocations allows researchers to tailor post-release management plans to each species' needs, thus maximizing the success of future translocation efforts while minimizing costs.
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Despite the key roles that dispersal plays in individual animal fitness and meta-population gene flow, it remains one of the least understood behaviors in many species. In large mammalian herbivores, dispersals might span long distances and thereby influence landscape-level ecological processes, such as infectious disease spread. Here, we describe and analyze an exceptional long-distance dispersal by an adult white-tailed deer (Odocoileus virginianus) in the central United States. We also conducted a literature survey to compare the dispersal to previous studies. This dispersal was remarkable for its length, duration, and the life history stage of the dispersing individual. Dispersal is typical of juvenile deer seeking to establish postnatal home ranges, but this dispersal was undertaken by an adult male (age = 3.5). This individual dispersed ~300 km over a 22-day period by moving, on average, 13.6 km/day and achieving a straight-line distance of ~215 km, which was ~174 km longer than any other distance recorded for an adult male deer in our literature survey. During the dispersal, which occurred during the hunting season, the individual crossed a major river seven times, an interstate highway, a railroad, and eight state highways. Movements during the dispersal were faster (mean = 568.1 m/h) and more directional than those during stationary home range periods before and after the dispersal (mean = 56.9 m/h). Likewise, movements during the dispersal were faster (mean = 847.8 m/h) and more directional at night than during the day (mean = 166.4 m/h), when the individual frequently sheltered in forest cover. This natural history event highlights the unpredictable nature of dispersal and has important implications for landscape-level processes such as chronic wasting disease transmission in cervids. More broadly, our study underscores how integrating natural history observations with modern technology holds promise for understanding potentially high impact but rarely recorded ecological events.
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Recently, statistical population models using age-at-harvest data have seen increasing use for monitoring of harvested wildlife populations. Even more recently, detailed evaluation of model performance for long-lived, large game animals indicated that the use of random effects to incorporate unmeasured environmental variation, as well as second-stage Horvitz-Thompson-type estimators of abundance, provided more reliable estimates of total abundance than previous models. We adapt this new modeling framework to small game, age-at-harvest models with only young-of-the-year and adult age classes. Our Monte Carlo simulation results indicate superior model performance for the new modeling framework, evidenced by lower bias and proper confidence interval coverage. We apply this method to male wild turkey harvest in the East Ozarks turkey productivity region, Missouri, USA, where statistical population reconstruction indicates a relatively stationary population for 1996-2010.