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Objective: Hepatitis B is an infectious deoxyribonucleic acid virus which can cause significant morbidity and mortality. There is no current definitive treatment, however in the United States immunization is widely available. A paper published by the Advisory Committee on Immunization Practices/Centers for Disease Control (ACIP/CDC) in 2018 made updated recommendations regarding vaccination practices in the United States. The most notable change made was that all healthy newborns weighing ≥2000 g with a negative hepatitis B-status mother should receive hepatitis B immunization within 24 hours of birth. This quality improvement project studied the effect of the electronic medical record newborn admission order set, altered to reflect current societal recommendations, and the resulting newborn hepatitis B immunization rates. Methods: The electronic medical record admission order set was modified to reflect the most recent recommendations made by ACIP/CDC. Hepatitis B immunization rates were then analyzed prior to and following the order set changes. Results: The most significant effect was seen in the overall rate of hepatitis B immunization achieved prior to hospital discharge. In the 12 months before order set modifications were implemented the rate was 9.5%. Following electronic medical record changes it improved to over 90%. In addition, the immunization rate performed within the first 24 hours increased from 74.1% to 91.1%. Finally, these records were made accessible to outpatient providers via a statewide immunization database. Conclusions: This project serves as an example of how modifying order sets can have a dramatic effect on ordering practices and therefore allows for quality improvement.
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Theoretically, markers that distinguish European from West African ancestry can be used to examine the origin of chromosomal segments in individual African Americans. In this study, putative ancestral origin was examined by using haplotypes estimated from genotyping 268 African Americans for 29 ancestry informative markers spaced over a 60-cM segment of chromosome 5. Analyses using a Bayesian algorithm (STRUCTURE) provided evidence that blocks of individual chromosomes derive from one or the other parental population. In addition, modeling studies were performed by using hidden real marker data to simulate patient and control populations under different genotypic risk ratios. Ancestry analysis showed significant results for a genotypic risk ratio of 2.5 in the African American population for modeled susceptibility genes derived from either putative parental population. These studies suggest that admixture mapping in the African American population can provide a powerful approach to defining genetic factors for some disease phenotypes.
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Población Negra/genética , Negro o Afroamericano/genética , Población Blanca/genética , Negro o Afroamericano/etnología , Mapeo Cromosómico , Cromosomas Humanos Par 5/genética , Simulación por Computador , Etnicidad/genética , Marcadores Genéticos/genética , Variación Genética/genética , Genética de Población , Genotipo , Haplotipos/genética , Haplotipos/inmunología , HumanosRESUMEN
Markers with large differences in allele frequencies between ethnicities provide ancestry information that can be applied to genetic studies. We identified over 100 biallelic ancestry informative markers (AIMs) with large allele frequency differences between European Americans (EA) and Pima Amerindians from laboratory and database screens. For 35 of these markers, Mayan, Yavapai and Quechuan Amerindians were genotyped and compared with EA and Pima allele frequencies. Markers with large allele frequency differences between EA and one Amerindian tribe showed only small differences between the Amerindian tribes. Examination of structure in individuals demonstrated a clear separation of subjects of European from those of Amerindian ancestry, and similarity between individuals from disparate Amerindian populations. The AIMs demonstrated the variation in ancestral composition of individual Mexican Americans, providing evidence of applicability in admixture mapping and in controlling for structure in association tests. In addition, a high percentage of single-nucleotide polymorphisms (SNPs) selected on the basis of large frequency differences between EA and Asian populations had large allele frequency differences between EA and Amerindians, suggesting an efficient method for greatly expanding AIMs for use in admixture mapping/structure analysis in Mexican Americans. Together, these data provide additional support for the practical application of admixture mapping in the Mexican American population.
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Pueblo Asiatico/genética , Indígenas Centroamericanos/genética , Americanos Mexicanos/genética , Población Blanca/genética , Alelos , Mapeo Cromosómico , Estudios de Factibilidad , Frecuencia de los Genes , Marcadores Genéticos , Variación Genética , Genética de Población , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Admixture mapping is a potentially powerful tool for mapping complex genetic diseases. For application of this method, admixed individuals must have genomes composed of large segments derived intact from each founding population. Such segments are thought to be present in African Americans (AA) and should be demonstrable by examination of linkage disequilibrium (LD). Previous studies using a variety of polymorphic markers have variably reported long-range LD or rapid decay of LD. To further define the extent and characteristics of LD caused by admixture in the AA population, the current study utilized a set of 52 diallelic markers that were selected for large standard variances between putative representatives of the founder populations. LD was examined in over 250 marker-pairs, including linked markers from four different chromosomal regions and an equal number of matched unlinked comparisons. In the representative founder populations, strong LD was not observed for markers separated by more than 10 kb. In contrast, results indicated significant LD ( P<0.001, D'>0.3) in AA over large genomic segments exceeding 10 centiMorgans (cM) and 15 megabases (Mb). Only marginally significant LD was present between unlinked markers in this population, suggesting that choosing appropriate levels of significance for admixture mapping can minimize false positive results. The ability to detect LD for extended chromosomal segments in AA decayed not only as a function of the distance between markers, but also as a function of the standard variance of the markers. This examination of several genomic segments provides strong evidence that appropriate selection of informative markers is a crucial prerequisite for the application of admixture mapping to the AA population.
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Población Negra/genética , Cromosomas Humanos Par 5/genética , Efecto Fundador , Marcadores Genéticos , Desequilibrio de Ligamiento , Negro o Afroamericano , Variación Genética , Genética de Población , Genoma Humano , Humanos , Población Blanca/genéticaRESUMEN
Markers informative for ancestry are necessary for admixture mapping and improving case-control association analyses. In particular, African Americans are an admixed population for which genetic studies require accurately evaluating admixture. This will require markers that can be used in African Americans to determine if a given genomic region is of European or African ancestry. This report shows that, despite studies indicating high intra-African sequence variation, markers with large inter-ethnic differences have only small variations in allele distribution among divergent African populations and should be valuable for evaluating admixture in complex disease genetic studies.
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Marcadores Genéticos , Variación Genética , África/etnología , Europa (Continente)/etnología , HumanosRESUMEN
Mapping by admixture linkage disequilibrium (MALD) is a potentially powerful technique for the mapping of complex genetic diseases. The practical requirements of this method include (a) a set of markers spanning the genome that have large allele-frequency differences between the parental ethnicities contributing to the admixed population and (b) an understanding of the extent of admixture in the study population. To this end, a DNA-pooling technique was used to screen microsatellite and diallelic insertion/deletion markers for allele-frequency differences between putative representatives of the parental populations of the admixed Mexican American (MA) and African American (AA) populations. Markers with promising pooled differences were then confirmed by individual genotyping in both the parental and admixed populations. For the MA population, screening of >600 markers identified 151 ethnic-difference markers (EDMs) with delta>0.30 (where delta is the absolute value of each allele-frequency difference between two populations, summed over all marker alleles and divided by two) that are likely to be useful for MALD analysis. For the AA population, analysis of >400 markers identified 97 EDMs. In addition, individual genotyping of these markers in Pima Amerindians, Yavapai Amerindians, European American (EA) individuals, Africans from Zimbabwe, MA individuals, and AA individuals, as well as comparison to the CEPH genotyping set, suggests that the differences between subpopulations of an ethnicity are small for many markers with large interethnic differences. Estimates of admixture that are based on individual genotyping of these markers are consistent with a 60% EA:40% Amerindian contribution to MA populations and with a 20% EA:80% African contribution to AA populations. Taken together, these data suggest that EDMs with large interpopulation and small intrapopulation differences can be readily identified for MALD studies in both AA and MA populations.
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Población Negra/genética , Mapeo Cromosómico/métodos , Desequilibrio de Ligamiento/genética , Americanos Mexicanos/genética , Repeticiones de Microsatélite/genética , Negro o Afroamericano , Alelos , Frecuencia de los Genes , Genoma Humano , Humanos , Indígenas Sudamericanos/genética , Mutagénesis Insercional/genética , Eliminación de Secuencia/genética , Población Blanca/genéticaRESUMEN
Inheritance of one of three primary mutations at positions 11778, 3460 or 14484 of the mitochondrial genome in subunits of Complex I causes Leber's Hereditary Optic Neuropathy (LHON), a specific degeneration of the optic nerve, resulting in bilateral blindness. It has been unclear why inheritance of a systemic mitochondrial mutation would result in a specific neurodegeneration. To address the neuron-specific degenerative phenotype of the LHON genotype, we have created cybrids using a neuronal precursor cell line, Ntera 2/D1 (NT2), containing mitochondria from patient lymphoblasts bearing the most common LHON mutation (11778) and the most severe LHON mutation (3460). The undifferentiated LHON-NT2 mutant cells were not significantly different from the parental cell control in terms of mtDNA/nDNA ratio, mitochondrial membrane potential, reactive oxygen species (ROS) production or the ability to reduce Alamar Blue. Differentiation of NT2s resulted in a neuronal morphology and neuron-specific pattern of gene expression, and a 3-fold reduction in mtDNA/nDNA ratio in both mutant and control cells; however, the differentiation protocol yielded significantly less LHON cells than controls, by 30%, indicating either a decreased proliferative potential or increased cell death of the LHON-NT2 cells. Differentiation of the cells to the neuronal form also resulted in significant increases in ROS production in the LHON-NT2 neurons versus controls, which is abolished by rotenone, a specific inhibitor of Complex I. We infer that the LHON genotype requires a differentiated neuronal environment in order to induce increased mitochondrial ROS, which may be the cause of the reduced NT2 yield; and suggest that the LHON degenerative phenotype may be the result of an increase in mitochondrial superoxide which is caused by the LHON mutations, possibly mediated through neuron-specific alterations in Complex I structure.