Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Gallagher ML[original query] |
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Maternal smoking, xenobiotic metabolizing enzyme gene variants, and gastroschisis risk.
Jenkins MM , Reefhuis J , Gallagher ML , Mulle JG , Hoffmann TJ , Koontz DA , Sturchio C , Rasmussen SA , Witte JS , Richter P , Honein MA . Am J Med Genet A 2014 164A (6) 1454-63 Maternal smoking during pregnancy is one proposed risk factor for gastroschisis, but reported associations have been modest, suggesting that differences in genetic susceptibility might play a role. We included 108 non-Hispanic white and 62 Hispanic families who had infants with gastroschisis, and 1,147 non-Hispanic white and 337 Hispanic families who had liveborn infants with no major structural birth defects (controls) in these analyses. DNA was extracted from buccal cells collected from infants and mothers, and information on periconceptional smoking history was obtained from maternal interviews, as part of the National Birth Defects Prevention Study. We analyzed five polymorphisms in three genes that code for enzymes involved in metabolism of some cigarette smoke constituents (CYP1A1, CYP1A2, and NAT2). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) independently for maternal smoking and maternal and infant gene variants, and to assess joint associations of maternal smoking and maternal or infant gene variants with gastroschisis. In analyses adjusted for maternal age at delivery and stratified by maternal race-ethnicity, we identified three suggestive associations among 30 potential associations with sufficient numbers to calculate ORs: CYP1A1*2A for non-Hispanic white mothers who smoked periconceptionally (aOR = 0.38, 95% CI 0.15-0.98), and NAT2*6 for Hispanic non-smoking mothers (aOR = 2.17, 95% CI 1.12-4.19) and their infants (aOR = 2.11, 95% CI 1.00-4.48). This analysis does not support the occurrence of effect modification between periconceptional maternal smoking and most of the xenobiotic metabolizing enzyme gene variants assessed. |
Qualitative assessment of study materials and communication strategies used in studies that include DNA collection.
Jenkins MM , Reed-Gross E , Barfield WD , Prue CE , Gallagher ML , Rasmussen SA , Honein MA . Am J Med Genet A 2011 155A (11) 2721-31 To understand motivations and barriers to participation in studies that include DNA collection, focus group discussions were held with mothers who had participated in a case-control study of birth defects. Recruited mothers had completed an interview and had received a mailed kit containing cytobrushes to collect buccal cells for DNA from herself, her infant, and her infant's father. Six moderator-led focus groups were attended by a total of 38 women residing in Atlanta, Georgia. Focus groups were segmented by DNA collection status (biologics participants or nonparticipants), infant case-control status, infant birthweight, and maternal race and ethnicity. This report assesses maternal attitudes toward study materials and communication strategies. Across groups, respondents expressed concern about how their contact information was obtained. Study materials were described as clear and professional by most women, although some respondents reported confusion about disclosure of individual genetic results. Respondents generally reported that monetary incentives were not a motivation to participate, but increased perceived study legitimacy. Biologics nonparticipants expressed concerns about kit component sterility; government involvement; and DNA sample use, storage, and disposal. Respondents suggested that investigators provide feedback on whether sample collection was performed correctly and provide materials targeted to fathers to help alleviate paternal skepticism. Participation in DNA collection might be improved by strengthening study materials and communication strategies. Published 2011. This article is a U.S. Government work and is in the public domain in the USA. |
Evaluation of mailed pediatric buccal cytobrushes for use in a case-control study of birth defects.
Gallagher ML , Sturchio C , Smith A , Koontz D , Jenkins MM , Honein MA , Rasmussen SA . Birth Defects Res A Clin Mol Teratol 2011 91 (7) 642-8 BACKGROUND: Buccal cell collection is a convenient DNA collection method; however, little attention has been given to the quality of DNA obtained from pediatric populations. The purpose of this study was to determine the effect of a modified cytobrush collection method on the yield and quality of infant buccal DNA collected as part of a population-based case-control study of birth defects. METHODS: Cytobrushes were collected from infants, mothers, and fathers using a standard collection method in 1997 to 2003 and a modified protocol that allows air-drying of the cytobrushes after collection from 2003 to the present. Yield and quality of DNA from 1057 cytobrushes was assessed by quantitative PCR and short tandem repeat (STR) genotyping, respectively. RESULTS: Air-dried cytobrushes from infants had higher median DNA yields (1300 ng) and STR completion rates (99.5%) than standard collection method cytobrushes (60 ng and 59.5%, respectively). A subset of DNA aliquots was genotyped for six single nucleotide polymorphisms (SNPs). Aliquots from both collection methods that passed the quality protocol (DNA concentration >1 ng/mul, and successful amplification of ≥1 STR) had high genotype completion rates (99-100%). The median DNA yield following whole genome amplification was more than twofold higher for air-dried than standard collection specimens (p < 0.001). CONCLUSION: Yield and quality of buccal DNA collected from infants are improved by using a method that incorporates air-drying; however, DNA collected by both methods is suitable for genotyping if stringent quality control procedures are instituted. These findings may be helpful for future epidemiologic studies of birth defects and other adverse pediatric outcomes. Birth Defects Research (Part A) 2011. (c) 2011 Wiley-Liss, Inc. |
Maternal attitudes toward DNA collection for gene-environment studies: a qualitative research study
Jenkins MM , Reed-Gross E , Rasmussen SA , Barfield WD , Prue CE , Gallagher ML , Honein MA . Am J Med Genet A 2009 149A (11) 2378-86 To assess attitudes toward DNA collection in an epidemiological study, focus groups were assembled in September 2007 with mothers who had participated in a case-control study of birth defects. Each recruited mother previously had completed an interview and had received a mailed kit containing cytobrushes to collect buccal cells for DNA from herself, her infant, and her infant's father during the period July 2004 through July 2007. A total of 38 mothers attended six focus groups comprising: (1) non-Hispanic Black mothers of case infants who participated or (2) did not participate in DNA collection, (3) mothers of any race or ethnicity who had case infants of low birth weight who participated or (4) did not participate in DNA collection, and (5) non-Hispanic Black mothers of control infants who participated or (6) did not participate in DNA collection. Moderator-led discussions probed maternal attitudes toward providing specimens, factors that influenced decision making, and collection method preferences. Biologics participants reported that they provided DNA for altruistic reasons. Biologics nonparticipants voiced concerns about government involvement and how their DNA will be used. Information provided (or not provided) on DNA use, storage, and disposal influenced decision making. Biologics participants and nonparticipants reported that paternal skepticism was a barrier to participation. All mothers were asked to rank DNA collection methods in terms of preference (cytobrushes, saliva, mouthwash, newborn blood spots, and blood collection). Preferred methods were convenient and noninvasive. Better understanding attitudes toward DNA collection and preferred collection methods might allow more inclusive participation and benefit future studies. (c) 2009 Wiley-Liss, Inc. |
Rapid detection of the CYP2A6*12 hybrid allele by Pyrosequencing technology
Koontz DA , Huckins JJ , Spencer A , Gallagher ML . BMC Med Genet 2009 10 80 BACKGROUND: Identification of CYP2A6 alleles associated with reduced enzyme activity is important in the study of inter-individual differences in drug metabolism. CYP2A6*12 is a hybrid allele that results from unequal crossover between CYP2A6 and CYP2A7 genes. The 5' regulatory region and exons 1-2 are derived from CYP2A7, and exons 3-9 are derived from CYP2A6. Conventional methods for detection of CYP2A6*12 consist of two-step PCR protocols that are laborious and unsuitable for high-throughput genotyping. We developed a rapid and accurate method to detect the CYP2A6*12 allele by Pyrosequencing technology. METHODS: A single set of PCR primers was designed to specifically amplify both the CYP2A6*1 wild-type allele and the CYP2A6*12 hybrid allele. An internal Pyrosequencing primer was used to generate allele-specific sequence information, which detected homozygous wild-type, heterozygous hybrid, and homozygous hybrid alleles. We first validated the assay on 104 DNA samples that were also genotyped by conventional two-step PCR and by cycle sequencing. CYP2A6*12 allele frequencies were then determined using the Pyrosequencing assay on 181 multi-ethnic DNA samples from subjects of African American, European Caucasian, Pacific Rim, and Hispanic descent. Finally, we streamlined the Pyrosequencing assay by integrating liquid handling robotics into the workflow. RESULTS: Pyrosequencing results demonstrated 100% concordance with conventional two-step PCR and cycle sequencing methods. Allele frequency data showed slightly higher prevalence of the CYP2A6*12 allele in European Caucasians and Hispanics. CONCLUSION: This Pyrosequencing assay proved to be a simple, rapid, and accurate alternative to conventional methods, which can be easily adapted to the needs of higher-throughput studies. |
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