OBJECTIVES: The objective of this study is to determine factors which may affect Health Black Family Project members participation in the Minority Research Recruitment Database (MRRD), as established through the Center for Minority Health and the Family Health History initiative. METHODS: MRRD enrollment was offered to 799 African American individuals after participation in a Family Health History session. Of the 799 offered enrollment, 599 (75.0%) agreed to enroll in the database and to be contacted regarded clinical research studies for which they may qualify. Factors assessed to determine their influence on willingness to enroll include demographic data, research attitudes, objective and perceived disease risks, weight, physical activity level, student interviewer, and the degree of control which people believe they possess over their personal health as measured by the Multidimensional Health Locus of Control questionnaire. Chi-square analyses and logistic regression were undertaken to compare these factors with willingness to enroll in the database. RESULTS: Analyses indicate that the following factors significantly affect willingness to enroll in the MRRD: being over age 65, health insurance status, research attitudes, previously declining research participation, reaction to incentives of money and free medical care, how much they believe family and friends benefit from research, degree to which they believe diet contributes to disease risk, student interviewer, Multidimensional Health Locus of Control Powerful Others scale, and self-described weight. Logistic regression of selected variables determined that reaction to monetary incentives, student interviewer, and self-described weight are key factors which may influence MRRD enrollment. CONCLUSIONS: The infrastructure of the MRRD has been shown to be an effective method for recruiting African Americans into a research database. Several factors have emerged as important in the determination of willingness to enroll, which represent both replications of the known literature and new findings unique to this research. PUBLIC HEALTH SIGNIFICANCE: African Americans are underrepresented in many areas of medical and public health research. More effective strategies are needed to increase recruitment into research studies by understanding factors presented here which may play a role in an individuals choice to participate in research.

Bipolar disorder is a mood disorder that affects about 1% of the population, representing a significant public health issue. Bipolar disorder can be associated with substance abuse problems, unemployment, increased marital dysfunction, and increased use of health services. Twin studies provide evidence that genetics plays a role in the etiology of bipolar disorder with heritability estimates as high as 93% in some studies. Molecular genetic studies were initially promising, but no genes with large effect sizes have been discovered. There is also evidence that suggests a multifactorial inheritance pattern. Consequently, genetic testing is not yet available. However, as advances are made in the understanding of genetics and psychiatric disorders, it is expected that the demand for genetic counseling for bipolar disorder will increase. Genetic counselors are well-equipped to educate patients and family members about the condition, to discuss their concerns about the risk of bipolar disorder, and to offer genetic testing should it become available. For this qualitative study, interviews were conducted to explore the opinions and perceptions of individuals with bipolar disorder and/or their siblings. The open-ended questions were designed to elicit the thoughts and attitudes about bipolar disorder and genetic counseling. Thematic analysis was performed on the transcripts from 10 interviews and the following themes were identified: excessive disease burden, variable causal attributions, desire for diagnostic test for BPD, and reproductive considerations.

Objectives/Research Questions: The purpose of this study was to assess existing curricula regarding HIV positive pregnant women in genetic counseling graduate programs. Methods: Genetic counseling programs were surveyed to assess existing curricula regarding prevention and treatment issues for HIV positive pregnant women. Programs were asked to identify their need for HIV-related educational materials, specifically issues and content needed to provide effective education for students and types of materials that would most benefit programs. Results: Of the 32 graduate genetic counseling programs, 26 (81.3%) responded to the survey. The data show that 65.4% currently offer HIV education in their curriculum. With regard to development of educational materials to address HIV in pregnancy, 64.3% (9/14) of programs that provide HIV education and 88.9% (8/9) of programs that provide no HIV education indicated they would benefit from development of these materials. The most commonly requested materials were webinars, PowerPoint presentations, and clinical case examples. Conclusions: The results of this study indicate a need for the development of additional educational materials addressing issues specific to HIV positive pregnant women and reduction of perinatal transmission. Through the Pennsylvania/MidAtlantic AIDS Education and Training Center, web-based seminars and other educational materials were developed for distribution to genetic counseling programs. Implications for Public Health: HIV is a major public health issue for all health-care providers who work with women of child-bearing age. Improving knowledge of HIV prevention and treatment in pregnant women is important for genetic counselors who may encounter HIV-positive pregnant women in their clinical practice.

Dental caries is the most prevalent chronic disease seen in children worldwide, and despite advancements in oral healthcare, many adults and children are still affected. The etiology of dental caries is complex, including environmental and genetic factors. Environmental factors such as fluoride exposure, oral hygiene, salivary function, diet, and bacterial flora have all been studied and found to contribute to dental caries experience. However, little is known about the genetic causes of dental caries. Candidate genes involved in enamel formation, tooth development, and taste have all been studied and found to be associated with dental caries. Matrix metalloproteinases are a multi-gene family responsible for degrading extracellular matrix (ECM) molecules. Their role in the oral environment involves ECM remodeling and degradation processes. Because the dentin of a tooth is composed primarily of an organic matrix, mostly collagen, it can pose as a potential substrate for MMP10. Recent initial GWAS results showed an association between MMP10 and dental caries [Personal Communication, Center for Craniofacial and Dental Genetics]. Based upon these initial GWAS findings, we performed a replication study to determine if the associations between MMP10 and dental caries seen in the initial GWAS were present in our population. We also studied genotype precision between our study and that of the initial GWAS. We genotyped 274 Caucasian individuals at SNP rs2276108 and 338 Caucasian individuals at SNP rs17293642 using a Taqman® SNP genotyping assay. Linear regression analysis using PLINK, adjusting for age, sex and site, found no association between the SNPs and dental caries in our sample population. Failure to replicate the initial GWAS findings in MMP10 suggests priority efforts should be given to exploring other candidate associations. The public health importance of identifying these genetic factors and understanding how they impact dental caries and other oral heatlh issues should open up new strategies for treatment and prevention and may elucidate new biological processes.

Bipolar disorder is a common and serious mood disorder that affects approximately 1% of the population. A major health concern, bipolar disorder can have profound effects on individuals, their family members and society. With heritability approaching 93% in some twin studies, the genetic etiology of bipolar disorder is under investigation. Molecular genetic studies have not revealed genes with large effect sizes. Based on the present information gained from twin, family and molecular genetic studies, a multifactorial inheritance pattern is suggested. As a result, genetic testing is not available for bipolar disorder. As genetic knowledge advances, however, it becomes increasingly important to imagine the role that genetic counseling may have for individuals with BPD and their family members. Thus, this study investigates the opinions and perceptions of individuals with bipolar disorder and/or their siblings on issues relevant to genetic counseling. A qualitative research design was employed. Tape-recorded phone interviews were conducted with twenty participants. Thematic analysis of the interview transcripts was utilized to characterize perceptions. Three main themes were identified: 1.) Individuals with bipolar disorder in their family appreciate the importance of a diagnosis and are concerned by perceived limitations with current methods of diagnosis. 2.) Bipolar disorder in the family can have profound effects on relationships, in both negative and positive ways. 3) Increased education and additional support may impact individuals with bipolar disorder and their families. Additionally, approximately 79% of individuals in this study expressed interest in pursuing genetic counseling to discuss additional information and risks for family members. In addition to showing the interest in genetic counseling expressed by these individuals and their siblings, these findings also may provide a better understanding of the needs of this population. This work has public health relevance as it describes how a common disease can impact individuals and their families and how genetic counseling may provide them with an additional source of support. This study may become increasingly relevant as our understanding of the genetics of bipolar disorder grows.

Cleft lip with or without an associated cleft palate (CL/P) is one of the most common congenital birth defects. Both the frequency with which it occurs and the high psychosocial and financial costs associated with CL/P contribute to a significant public health interest in the condition. Defining the spectrum of disability associated with CL/P will serve to improve treatment planning and caregiver education and may inform efforts to describe the etiology of this complex trait. The principal aim of this project was to test the hypothesis that significant olfactory dysfunction exists in individuals with repaired orofacial clefts (OFCs; cleft lip, with or without cleft palate ((CL/P) and isolated cleft palate (CP)) and their first degree relatives (FDRs). Two small studies and anecdotal reports suggest impaired olfaction in individuals with OFCs, but this is the first investigation of the olfactory phenotype in both cases and relatives. Genetic, physiologic, and developmental features of individuals with OFCs provide plausible explanations for this poorly explored phenomenon. Methods: The widely used and extensively validated University of Pennsylvania Smell Identification Test (UPSIT) - a "scratch and sniff" 40 item odor discrimination test - was employed to describe olfactory ability in a sample of 12 subjects with non-syndromic CL/P or CP and 39 of their unaffected FDRs. Control data was obtained from published norms on over 2000 individuals. Standard non-parametric and categorical statistics were used to test for group differences in olfactory performance. Results: The likelihood of having a smell deficit was increased nearly fivefold in the cases (OR=4.94; 95% CI 1.56-15.65) compared with controls. Similarly, the likelihood of having a smell deficit was increased nearly fourfold in the FDRs (OR=3.87; 95% CI 1.99-7.52) compared with controls. Cases scored significantly lower on the UPSIT compared with their FDRs (p<0.043), indicating that the olfactory deficit was greater in cases. This study provides the first evidence of olfactory deficits in the FDRs of OFC cases and confirms the existence of olfactory deficits in OFC patients.

Premature ovarian failure (POF), or premature ovarian insufficiency (POI), is characterized by the absence or early cessation of menstruation before the age of 40. Clinically this can be seen as primary amenorrhea, the complete absence of menstruation, or secondary amenorrhea, the development of amenorrhea due to cessation of ovarian function. POI affects approximately 1% of women under the age of 40 years and 0.1% of women under the age of 30. Most cases of POI are idiopathic, as only 10% have a known cause. We utilized SNP array technology to identify novel copy number variations (CNVs) in 89 women with POI. Illuminas (San Diego, CA, USA) HumanCNV370-Duo DNA Analysis BeadChip and Human660W-Quad v1 DNA Analysis BeadChip were used to identify microdeletions and microduplications on autosomal chromosomes. A total of 198 autosomal CNVs were identified ranging from 0.1 Mb to 3.4 Mb. The Database of Genomic Variants (DGV) was used as a control population. We identified seven novel microdeletions in our POI cohort, six of which contained gene-coding regions: 8q24.13, 10p15-p14, 10q23.31, 10q26.3, 15q25.2, and 18q21.32. Two of the novel microdeletions contained genes known to cause ovarian failure in knockout mice models, SYCE1 and CPEB1. Seventeen novel microduplications were also detected, with the majority of CNVs detected being on autosomal chromosomes rather than the X chromosome. This pilot study demonstrates an association between specific CNVs and POI and highlights the importance for studies with larger samples sizes to confirm the findings and further support the hypothesis. Furthermore, array technology may be a useful addition to conventional karyotyping when evaluating women with POI. Studies on the genetic factors of POI have public health significance because they search for genomic imbalances in a disease that affects 1% of the American population. Finding the genetic causes may lead to effective treatment methods and earlier recognition of those at risk, particularly before the onset of amenorrhea.

Objections: In April 2010, the National Collegiate Athletic Association (NCAA) approved mandatory testing for sickle cell trait status for all student athletes participating in Division I sports. Childrens Sickle Cell Program at Childrens Hospital of Pittsburgh offered genetic testing and counseling to all student athletes participating in Division I athletes at the University of Pittsburgh and Duquesne University. Methods: In addition, to assess the knowledge of sickle cell trait among the student athletes, along with the effect of genetic counseling, student athletes were asked to participate in a survey. A short survey was provided to the student athletes prior to their genetic counseling, with a short survey provided following the genetic testing (See Appendix A for IRB consent form and Appendix B for questionnaires). Results: Between the two Division I programs at the University of Pittsburgh and Duquesne University, 122 student athletes were tested of which, one athlete was diagnosed with sickle cell trait. Among the 122 student athletes tested, 80 participated in the surveys. Among those who participated, 57 (71%) were Caucasian, 16 (20%) were African American, and the remaining athletes were of mixed or other ethnic backgrounds. Prior to the genetic counseling session, 11% of the student athletes answered that they had never heard of sickle cell disease or sickle cell trait. Following the genetic counseling session, 89% of the student athletes had a good understanding of sickle cell trait, with 15% showing that they learned something from the genetic counseling session. Conclusions: Based on the data obtained from this study, student athletes may not have a good understanding of the testing that is mandated by the NCAA. Therefore, genetic counseling is strongly recommended to all student athletes prior to the carrier status testing. Implications for Public Health: Many issues surround the NCAA ruling mandating sickle cell trait testing. However, many are not focusing on the importance of the impact genetic testing has on an individual, particularly this age range involved. Genetic counseling needs to be considered when requiring these student athletes to undergo genetic testing for sickle cell trait.

PURPOSE: Every year, thousands of Americans pursue prenatal diagnosis of fetal aneuploidy though chorionic villus sampling (CVS) or amniocentesis. Because these procedures are invasive and carry an inherent risk for pregnancy loss, they are selectively offered to women who have an increased risk to have a child with a chromosome condition, such as aneuploidy. In order to identify pregnancies at an increased risk, several non-invasive screening methods have been developed. Although quite useful, these screening methods have limited accuracy and can only be completed during specific gestational age windows. Recent discovery of cell free fetal DNA in maternal circulation has created new and exciting possibilities for prenatal screening and non-invasive prenatal diagnosis. This research study explores shotgun next-generation sequencing of fetal DNA in maternal plasma as a method for non-invasive identification of fetal aneuploidy. METHODS: We carried out shotgun next-generation sequencing on samples of maternal plasma DNA obtained in the first trimester of pregnancies with confirmed aneuploidy and control pregnancies. Three Trisomy 21 samples were compared to four control samples in order to identify any differences in the amount of chromosomal material. RESULTS: We identified a statistically significant increase in chromosome 21 material in the cases of Trisomy 21 as compared to the control cases. IMPLICATIONS: This research demonstrates that shotgun next-generation sequencing of maternal plasma DNA can successfully identify Trisomy 21, showing that it is possible to detect fetal aneuploidy using this noninvasive method. This technology could potentially be used as a method of noninvasive screening for fetal aneuploidy, which is likely to have improved accuracy over other screening methods. Development of a screening test with greater sensitivity and specificity could have significant public health implications. This would not only provide more accurate identification of pregnancies at an increased risk for aneuploidy, but it would also reduce the number of false positives. This in turn would reduce the number of pregnancies that are unnecessarily classified as high risk, preventing avoidable parental anxiety and reducing the number of pregnancies that are put at unnecessary risk of invasive prenatal diagnostic procedures.

BACKGROUND: Cutis laxa (CL) is a group of disorders characterized by loose, inelastic, and redundant skin. The different types of CL are distinguished by clinical features, inheritance, and molecular findings. The objective of this study was to characterize the pulmonary phenotype of the different types of CL based on age of onset (congenital, acquired/late-onset, or unknown) and mutational status. The first aim of this study was to collect clinical data to better define the pulmonary involvement in cutis laxa. The second aim was to determine if heterozygous carriers of recessive types of cutis laxa are susceptible to chronic lung disease. METHODS: Clinical questionnaires, medical histories, and pulmonary function tests (PFTs) were used to collect clinical data on patients with a confirmed or suspected diagnosis of CL and unaffected first-degree relatives with a known mutation (carriers). The clinical data was then compared between the groups categorized by age of onset and between those with known mutations (mutational status). RESULTS: The clinical questionnaires and medical histories of 83 CL patients with 8 acquired/late-onset, 52 congenital, and 23 of unknown etiology and 5 carriers were analyzed. In addition, mutations have been identified in 27 of the 83 patients in ELN, FBLN4, FBLN5, ATP6V0A2, or LTBP4, and the 5 carriers had mutations in either FBLN4 or LTBP4. The most common respiratory responses amongst the patients included pneumonia (24.1%), tachypnea (15.7%), and emphysema (12.0%). The only statistically significant finding was dyspnea in acquired/late-onset patients. Of those with a known mutation, 15 reported pulmonary involvement, with 10 of these individuals having at least one LTBP4 mutation. For the 13 PFTs collected, the 10 CL patients ranged from normal lung function to very severe obstruction, and 3 carriers were deemed to have normal function. An important new finding was the presence of pulmonary obstructive disease in those with ATP6V0A2 mutations. CONCLUSION: These results demonstrate a high prevalence and significant heterogeneity of pulmonary complications in CL. Further research is needed to determine any correlation between specific pulmonary findings and genotypes. PUBLIC HEALTH SIGNIFICANCE: Chronic lung disease is a common cause of morbidity in the general population. Uncovering the genetic basis of chronic lung disease in inherited syndromes has the potential to identify key molecular targets for improved diagnosis and treatment of common respiratory ailments.