Rare variants found in clinical gene panels illuminate the genetic and allelic architecture of orofacial clefting.

Purpose: Orofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls.

Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases.

Background: Three genes clustered together on chromosome 12 comprise a group of hydroxycarboxylic acid receptors (HCARs): HCAR1, HCAR2, and HCAR3. These paralogous genes encode different G-protein coupled receptors responsible for detecting glycolytic metabolites and controlling fatty acid oxidation. Though better known for regulating lipid metabolism in adipocytes, more recently, HCARs have been functionally associated with breast cancer proliferation/survival; HCAR2 has been described as a tumor suppressor and HCAR1 and HCAR3 as oncogenes.

Gene panel screening for insight towards breast cancer susceptibility in different ethnicities.

African American breast cancer genetics is less understood compared to European American breast cancer susceptibility. Despite the many advantages of gene panel screening, studies investigating African American inherited breast cancer risk and comparing variant contributions between ethnicities are infrequent. Thus, 97 breast cancer-affected individuals of African and European descent from the Alabama Hereditary Cancer Cohort were screened using the research-based gene-panel, B.

A research-based gene panel to investigate breast, ovarian and prostate cancer genetic risk.

There is a need to investigate and better understand the inherited risk of cancer to ensure that clinical applications provide more accurate assessments and management strategies. Developing research-based next-generation sequencing gene panels that not only target (present-day) clinically actionable susceptibility genes but also genes that currently lack sufficient evidence for risk as well as candidate genes, such as those in DNA repair pathways, can help aid this effort. Therefore, gene panel B.

Establishment of the Alabama Hereditary Cancer Cohort - strategies for the inclusion of underrepresented populations in cancer genetics research.

Background: Historically, groups that are most susceptible to health and healthcare disparities have been underrepresented in medical research. It is imperative to explore approaches that can facilitate the recruitment of underrepresented individuals into research studies.

Methods: Two approaches, hospital and community-based recruitment (CBR), were developed and implemented over 36 months to study the genetics of hereditary breast cancer and associated cancers in Alabama, a medically underserved state with double the national percentage of self-identifying African Americans, establishing the Alabama Hereditary Cancer Cohort.