No Apparent Damage in the Thyroid of Transgenic Mice Expressing Antiapoptotic FLIP

FLIP is an antiapoptotic protein that has been demonstrated to play an important role in inflammation, cancer, and autoimmune diseases. However, it is not known whether increased expression of FLIP (FLICE inhibitory protein) in thyrocytes would alter the development of the thyroid and/or pathogenesis of thyroiditis. To examine the effects of overexpression of this antiapoptotic molecule on the thyroid, we have developed transgenic mouse lines that specifically express FLIP in thyrocytes. A DNA construct designed with an in-frame coding sequence for the E8 protein, a viral FLIP, was put under the control of the thyroglobulin (Tg) promoter (the Tg-FLIP transgene). In 8 of 12 resultant transgenic mouse lines, FLIP expression in thyrocytes driven by the Tg promoter was documented, and confirmed at RNA and protein levels. These Tg-FLIP transgenic mice were monitored for 1 year. Throughout the entire observation period, the transgenic mice remained alive and healthy without evidence of thyroid dysfunction. Adult mice were able to breed. Histologic examination of thyroids obtained at various time points did not reveal significant differences between transgenic mice and their control littermates. Therefore, transgenic mice with thyrocyte-specific expression of FLIP have normal thyroid development with no significant changes in thyroid cell death or proliferation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63191/1/thy.2006.16.1.pd

Family Communication in a Population at Risk for Hypertrophic Cardiomyopathy

Encouraging family communication is an integral component of genetic counseling; therefore, we sought to identify factors impacting communication to family members at risk for Hypertrophic Cardiomyopathy (HCM). Participants (N = 383) completed an online survey assessing: 1) demographics (gender, genetic test results, HCM family history, and disease severity); 2) illness representations; 3) family functioning and cohesiveness; 4) coping styles; 5) comprehension of HCM autosomal dominant inheritance; and 6) communication of HCM risk information to at‐risk relatives. Participants were a national sample of individuals with HCM, recruited through the Hypertrophic Cardiomyopathy Association. Data from 183 participants were analyzed using a logistic regression analysis, with family communication as a dichotomous dependent variable. We found that female gender and higher comprehension of autosomal dominant inheritance were significant predictors of participants’ communication of HCM risk information to all their siblings and children. Our results suggest that utilizing interventions that promote patient comprehension (e.g., a teaching‐focused model of genetic counseling) are important and may positively impact family communication within families with HCM.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147017/1/jgc40336.pd

A Case for Inclusion of Genetic Counselors in Cardiac Care

Recent advances in genetic testing for heritable cardiac diseases have led to an increasing involvement of the genetic counselor in cardiology practice. We present a series of cases collected from a nationwide query of genetics professionals regarding issues related to cost and utilization of genetic testing. Three themes emerged across cases: (1) choosing the most appropriate genetic test, (2) choosing the best person to test, and (3) interpreting results accurately. These cases demonstrate that involvement of a genetic counselor throughout the evaluation, diagnosis, and continuing management of individuals and families with inherited cardiovascular conditions helps to promote the efficient use of healthcare dollars

Julio C. TREBOLLÉ-BARRERA, Jehú y Joás. Texto y composición literaria de 2 Reyes 9-11, Edilva («Institución San Jerónimo», 17), Valencia 1984, 254 pp., 16 x 24. [RECENSIÓN]

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147202/1/jgc40689.pd

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

A survey of aortic disease biorepository participants’ preferences for return of research genetic results

There is ongoing debate on whether and what research genetic results to return to study participants. To date, no study in this area has focused on aortopathy populations despite known genes that are clinically actionable. Participants (n = 225, 79% male, mean age = 61 years) with an aortopathy were surveyed to assess preferences for receiving research genetic results. Participants were - very- or - extremely likely- to want results for pathogenic variants in aortopathy genes with implications for family members (81%) or that would change medical management (76%). Similarly, participants were - very- or - extremely likely- to want actionable secondary findings related to cancer (75%) or other cardiac diseases (70%). Significantly lower interest was observed for non- actionable findings- pathogenic variants in aortopathy genes that would not change medical management (51%) and variants of uncertain significance (38%) (p 63%) were accepting of any means of return; however, a substantial minority (18%- 38%) deemed certain technological means unacceptable (e.g., patient portal). Over 90% of participants reported that a range of health professionals, including cardiovascular specialists, genetics specialists, and primary care providers, were acceptable to return results. Participants with aortopathies are highly interested in research genetic results perceived to be medically actionable for themselves or family members. Participants are accepting of a variety of means for returning results. Findings suggest that research participants should be asked what results are preferred at time of informed consent and that genetic counseling may clarify implications of results that are not personally medically actionable.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/1/jgc41341_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/2/jgc41341-sup-0004-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/3/jgc41341.pd

A survey of aortic disease biorepository participants- preferences for return of research genetic results

There is ongoing debate on whether and what research genetic results to return to study participants. To date, no study in this area has focused on aortopathy populations despite known genes that are clinically actionable. Participants (n = 225, 79% male, mean age = 61 years) with an aortopathy were surveyed to assess preferences for receiving research genetic results. Participants were - very- or - extremely likely- to want results for pathogenic variants in aortopathy genes with implications for family members (81%) or that would change medical management (76%). Similarly, participants were - very- or - extremely likely- to want actionable secondary findings related to cancer (75%) or other cardiac diseases (70%). Significantly lower interest was observed for non- actionable findings- pathogenic variants in aortopathy genes that would not change medical management (51%) and variants of uncertain significance (38%) (p 63%) were accepting of any means of return; however, a substantial minority (18%- 38%) deemed certain technological means unacceptable (e.g., patient portal). Over 90% of participants reported that a range of health professionals, including cardiovascular specialists, genetics specialists, and primary care providers, were acceptable to return results. Participants with aortopathies are highly interested in research genetic results perceived to be medically actionable for themselves or family members. Participants are accepting of a variety of means for returning results. Findings suggest that research participants should be asked what results are preferred at time of informed consent and that genetic counseling may clarify implications of results that are not personally medically actionable.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/1/jgc41341_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/2/jgc41341-sup-0004-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168345/3/jgc41341.pd