Examining genetic counselors' implicit attitudes toward disability.

Genetic counselors have a unique role in healthcare that requires a balance between being a patient educator and patient advocate when discussing disability. This study aimed to determine genetic counselors' implicit attitudes toward disability, and identify what factors affect these implicit attitudes. Case scenarios involving disability were used to examine hypothetical estimates of time spent on different topics within a genetic counseling session. Implicit attitudes were measured using the validated Disability Attitudes Implicit Association Test (DA-IAT), and personal/professional experiences with disability were assessed. Analysis of 382 respondents of the electronic survey revealed that personal experience with individuals with disabilities was not significantly associated with implicit attitudes scores. In addition, results demonstrated that genetic counselors have a stronger bias toward ability (Dmean  = 0.62, Dstd  = ±0.45) compared to previous participants of the DA-IAT (p < .005). Practice specialty, length of time in the genetic counseling field, or whether the participant was a practicing counselor or genetic counseling student were not associated with implicit attitudes scores. The bias toward ability observed across practice specialties may be due to shared factors that influence interest in this field, but may also potentially reflect the inability of the DA-IAT to capture the complexity of genetic counselors' relationship to individuals with disability. This study emphasizes the importance of incorporating patients' individual definitions of disability into genetic counseling sessions and building an environment of patient advocacy and education around their personal perspectives and needs.

Chromatin conformation capture in the clinic: 4C-seq/HiC distinguishes pathogenic from neutral duplications at the GPR101 locus.

BACKGROUND: X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits. METHODS: We employed 4C/HiC-seq as a clinical tool to determine the functional impact of incidentally discovered GPR101 duplications on TAD integrity in three families. After defining duplications and breakpoints around GPR101 by clinical-grade and high-density aCGH, we constructed 4C/HiC chromatin contact maps for our study population and compared them with normal and active (X-LAG) controls. RESULTS: We showed that duplications involving GPR101 that preserved the centromeric invariant TAD boundary did not generate a pathogenic neo-TAD and that ectopic enhancers were not adopted. This allowed us to discount presumptive/suspected X-LAG diagnoses and GPR101 misexpression, obviating the need for intensive clinical follow-up. CONCLUSIONS: This study highlights the importance of TAD boundaries and chromatin interactions in determining the functional impact of copy number variants and provides proof-of-concept for using 4C/HiC-seq as a clinical tool to acquire crucial information for genetic counseling and to support clinical decision-making in cases of suspected TADopathies.