Pennsylvania Folklife Vol. 18, No. 1

• Tanning in Chester County, Pennsylvania, 1711-1850 • Chester County Widow Wills (1714-1800), A Folklife Source • Folk Elements in Scotch-Irish Presbyterian Communities • The Thomas Massey House • Passengers on the Ketch Endeavour • The Medical Plants of Berks County, Pennsylvania • Notes and Documents: A Dunkard Love Feast ; Jacob Graeff\u27s Reminiscences of Reading • Symposium on the Pennsylvania Dutch Dialect • Farm Dress: Folk-Cultural Questionnaire No. 9https://digitalcommons.ursinus.edu/pafolklifemag/1033/thumbnail.jp

Pennsylvania Folklife Vol. 18, No. 1

• Tanning in Chester County, Pennsylvania, 1711-1850 • Chester County Widow Wills (1714-1800), A Folklife Source • Folk Elements in Scotch-Irish Presbyterian Communities • The Thomas Massey House • Passengers on the Ketch Endeavour • The Medical Plants of Berks County, Pennsylvania • Notes and Documents: A Dunkard Love Feast ; Jacob Graeff\u27s Reminiscences of Reading • Symposium on the Pennsylvania Dutch Dialect • Farm Dress: Folk-Cultural Questionnaire No. 9https://digitalcommons.ursinus.edu/pafolklifemag/1033/thumbnail.jp

International Nonregimes: A Research Agenda1

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146934/1/j.1468-2486.2007.00672.x.pd

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia

Pharmacogenomics of osteonecrosis of the jaw

Osteonecrosis of the jaw (ONJ) is a rare but serious drug induced adverse event, mainly associated with the use of antiresorptive medications, such as intravenous (IV) bisphosphonates (BPs) in cancer patients. In this review, we evaluated all the pharmacogenomic association studies for ONJ published up to December 2018. To date, two SNPs (CYP2C8 rs1934951 and RBMS3 rs17024608) were identified to be associated with ONJ by two genome-wide association studies (GWAS). However, all six subsequent candidate gene studies failed to replicate these results. In addition, six discovery candidate gene studies tried to identify the genetic markers in several genes associated with bone remodeling, bone mineral density, or osteoporosis. After evaluating the results of these 6 studies, none of the SNPs was significantly associated with ONJ. Recently, two whole-exome sequencing (WES) analysis (including one from our group) were performed to identify variants associated with ONJ. So far, only our study successfully replicated discovery result indicating SIRT1 SNP rs7896005 to be associated with ONJ. However, this SNP also did not reach genome-wide significance. The major limitations of these studies include lack of replication phases and limited sample sizes. Even though some studies had larger sample sizes, they recruited healthy individuals as controls, not subjects treated with BPs. We conclude that a GWAS with a larger sample size followed by replication phase will be needed to fully investigate the pharmacogenomic markers of ONJ